Category Archives: Molecular Medicine

image:A tiny, touch-based sensor uses sweat to detect the level of lithium in the body. view more

Credit: Jialun Zhu and Shuyu Lin

CHICAGO, Aug. 21, 2022 Lithium can alleviate the symptoms of bipolar disorder and depression if taken in just the right amount. Too little wont work, while too much can bring on dangerous side effects. To precisely monitor the amount of this medication in the body, patients must undergo invasive blood tests. But today, scientists report the invention of a tiny sensor that detects lithium levels from sweat on the surface of a fingertip in as little as 30 seconds, without a trip to the clinic.

The researchers will present their results today at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid meeting being held virtually and in-person Aug. 2125, with on-demand access available Aug. 26Sept. 9. The meeting features nearly 11,000 presentations on a wide range of science topics.

Not only must lithium be taken at a certain dosage, but patients often struggle to take it as prescribed and may miss pills. So, when the medication doesnt appear to be working, health care providers need to know how much medication the patient is actually swallowing. But current options for monitoring have significant drawbacks. For example, blood draws produce accurate results, but they are invasive and time consuming. Pill counters, meanwhile, dont directly measure the intake of the medication. To address these limitations, the team turned to another body fluid.

Although it may not be visible, the human body constantly produces sweat, often only in very small amounts, says Shuyu Lin, Ph.D., a postgraduate student researcher who is co-presenting the work with graduate student Jialun Zhu at the meeting. Small molecules derived from medication, including lithium, show up in that sweat. We recognized this as an opportunity to develop a new type of sensor that would detect these molecules.

Through a single touch, our new device can obtain clinically useful molecular-level information about what is circulating in the body, says Sam Emaminejad, Ph.D., the projects principal investigator, who is at the University of California, Los Angeles (UCLA). We already interact with a lot of touch-based electronics, such as smart phones and keyboards, so this sensor could integrate seamlessly into daily life.

Devising a sensor to detect lithium presented some technical challenges, however. Sweat is generally only present in minute amounts, but the electrochemical sensing needed to detect charged particles of lithium required an aqueous, or watery, environment. To provide it, the team engineered a water-based gel containing glycerol. This extra ingredient prevented the gel from drying out and created a controlled environment for the electronic portion of the sensor.

To trap the lithium ions after they traversed the gel, the team used an ion-selective electrode. The accumulating ions generate a difference in electrical potential compared with a reference electrode. The researchers used this difference to infer the concentration of lithium present in sweat. Together, these components comprise a tiny, rectangular sensor that is smaller than the head of a thumbtack and can detect lithium in about 30 seconds. The sensor is still in the preliminary testing phase, but ultimately, the researchers envision incorporating it into a larger, yet-to-be designed system that provides visual feedback to the provider or the patient.

After characterizing the sensor using an artificial fingertip, the team recruited real people to test it, including one person on a lithium treatment regimen. The researchers recorded this persons lithium levels before and after taking the medication. They found that these measurements fell close to those derived from saliva, which prior research has shown to accurately measure lithium levels. In the future, the researchers plan to study the effects of lotion and other skin products on the sensors readings.

This technology also has applications beyond lithium. Emaminejad is developing similar touch-based sensors to monitor alcohol and acetaminophen, a painkiller also known as Tylenol, while also exploring the possibility of detecting other substances. The complete sensing systems could include additional features, such as encryption secured by a fingerprint, or, for substances prone to abuse, a robotic dispensing system that releases medication only if the patient has a low level in their bloodstream.

The researchers acknowledge support and funding from the National Science Foundation, Brain and Behavior Foundation, Precise Advanced Technologies and Health Systems for Underserved Populations and the UCLA Henry Samueli School of Engineering and Applied Sciences.

ACS Fall 2022 will be a vaccination-required and mask-recommended event for all attendees, exhibitors, vendors and ACS staff who plan to participate in-person in Chicago. For detailed information about the requirement and all ACS safety measures, please visit the ACS website.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the worlds scientific knowledge. ACS main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive press releases from the American Chemical Society, contact newsroom@acs.org.

Note to journalists: Please report that this research was presented at a meeting of the American Chemical Society.

Follow us:Twitter|Facebook|LinkedIn|Instagram

TitleTouch-based non-invasive lithium monitoring using an organohydrogel-based sensing interface

AbstractLithium salt is one of the most widely-used psychiatric medications for individuals with bipolar disorder. Due to its narrow therapeutic window (~ 0.6 - 1.2 mM) and high nonadherence rate (~ 40%), it needs to be closely monitored to maximize the treatment efficacy. Standard practices of lithium monitoring for precise dosing are confined to centralized hospitals and involve invasive blood draw and high-cost lab-based analysis with long turnaround time. Moreover, currently there is no direct lithium adherence monitoring available, and the indirect monitoring solutions (e.g., pill counters) are incapable of verifying the actual intake event (inherently non-specific).

Overcoming these limitations, here, we developed a touch-based non-invasive lithium monitoring solution for decentralized lithium pharmacotherapy management. This solution is based on a hydrogel coated-sensing interface that collects and analyzes (in-situ) the flux of circulating lithium molecules that partition onto fingertips. This interface was constructed using a thin organohydrogel-coated lithium ion-selective electrode (TOH-ISE), where the TOH coating was specially engineered to render stabilized conditions for sensing. In particular, by adopting a water-glycerol bi-solvent matrix, the gel was endowed with anti-dehydration property (negligible weight loss for > 2 weeks storage in an ambient environment), resolving the dehydration challenge of previously-reported hydrogel-based interfaces. Furthermore, in the devised interface configuration, the TOH coating serves as a controlled micro-environment to condition the ISE in-situ; thus, it minimizes the ISE signal drift (a key challenge prohibiting the translation of ISEs in real-life applications).

To illustrate the clinical utility of our solution, the developed touch-based sensing interface was tested on a patient prescribed with lithium-based medicine, where the elevation of the circulating drug levels after the medicine intake was successfully captured. Collectively, our preliminary results demonstrate the suitability of our touch-based solution for lithium adherence monitoring, and more broadly for managing lithium-based pharmacotherapy.

View post:
Sensor could help patients stay on top of their meds - EurekAlert

Centre of Excellence will focus on creating unparalleled medical discoveries to transform healthcare delivery

Trivitron Healthcare, a global manufacturer of medical devices has constantly strived towards novel innovation and applications to transform healthcare with quality products, services & smart ventures. For millions of healthcare practitioners across the world, Trivitron is known for trust, quality, safety, and innovationdriven products. Further to cater to the growing healthcare needs, a Centre of Excellence (CoE) with state-of-the-art R&D and Manufacturing facilities was launched on 19th August 2022 at AMTZ Campus, Vishakhapatnam, India by Prof. Ajay Kumar Sood, Principal Scientific Advisor to the Government of India and Prof. (Dr) Balram Bhargava, Former Director General, Indian Council of Medical Research.

At the inauguration, Dr GSK Velu, Chairman & Managing Director, Trivitron Healthcare said: Trivitron is committed to providing futuristic applications by encompassing advanced R&D, which will be coupled with strong manufacturing capabilities under the supervision of leading scientists and industry experts in this center which spans over 43,000 square feet area. This centre will implement research and innovation in the field of metabolomics, genomics, newborn screening, and molecular diagnostics and bring out cost-effective and affordable medical technology products and services. With 15 certified manufacturing facilities in India, USA, Finland, Turkey & China, Trivitron spearheads innovation in the field of in-vitro diagnostics, medical imaging and critical care solutions.

By harnessing the enormous power of genomic research and Trivitrons expertise in advanced diagnostics, this CoE will focus on creating unparalleled medical discoveries to transform healthcare delivery. The new centre is equipped with state-of-art infrastructure to support the entire product & process development lifecycle at the respective domain specific labs to achieve optimal scale-up to industrial production.

A great venture to futuristic medicine and diagnosis

IVD CE-approved kits for various newborn screening, infectious, non-infectious diseases and cancer markers based on RT-PCR, ELISA, Rapid cards/POCT, clinical chemistry and CLIA will be manufactured at this facility. Since all the components are made in-house, Trivitron will have the fastest turnaround time in the country. The major focus of this facility will be on the manufacturing of genomics-based kits and reagents. This will include the synthesis of customised primers and probes for RTPCR based screening kits, enzymes, master mixes etc.

The centre includes an Advanced Genomics and Molecular diagnostics facility for developing kits and reagents for Next Generation Sequencing (NGS) and oligonucleotide synthesis (synthesis of customised primers and Taq Man Chemistry dual labelled probes), Protein Chemistry (design and expression of different recombinant enzymes and proteins), cell culture and analytical lab. The company plans to manufacture all the raw materials and components of molecular diagnostics, NBS, and NGS in-house following advanced protocols and research approaches.

The new centre of Trivitron will have provision to manufacture 300 million RTPCR tests and over 70 million tests of Rapid Card/POCT per annum. Additionally, more than 100 million tests can be manufactured for genomics, ELISA, CLIA, NBS and other diagnostics kits

Read more from the original source:
Trivitron Healthcare launches CoE in metabolomics, genomics, newborn screening and molecular diagnostics - Express Healthcare

Introduction

Pain is an unpleasant sensory and emotional perception associated with actual or underlying tissue pathology, which can bring major clinical, social, and economic problems in communities around the world. Notably, pain appears to have a greater negative effect on the quality of life than other diseases, and is also the greater cause of disability around the world.1 It was estimated that more than 20% of the population visit the clinic with pain as the main complaint each year.2 Additionally, pain also creates enormous economic pressure on society, with a total cost of about 3.0% of GDP.3 Unfortunately, treatment options for pain are poorly targeted due to the complex etiology and recurring symptoms. As commonly identified, pain disease can be the classification by time (acute or chronic), etiology (traumatic, pathological, neurogenic, etc.), location (head and neck, spine and joint, etc.) and other methods. Pharmacological therapy options can relieve pain in a short time but the safety concerns of using muscle relaxants, non-steroidal anti-inflammatory drugs or other painkillers need to be fully evaluated. Thereby, effective complementary and alternative therapies attract both patients and practitioners.4

Moxibustion, a typical therapeutic procedure of traditional Chinese medicine (TCM), which restores the function of visceral organs and meridians by applying heat from burning herbs such as moxa to a certain area or acupoints, is widely sought after and used in the current healthcare system.5 It cures disease by stimulating specific spots on the skin to treat many medical conditions such as asthma, colds and influenza, irritable bowel syndrome (IBS), cancer-related fatigue, disorders of the spinal column, pain, and others.610 Accumulating evidence indicates that the combined effect of thermal effects and non-thermal radiation effects of pharmacological responses such as smoke and moxa extracts contribute significantly to the overall analgesic efficacy of moxibustion treatment.11

Preliminary studies were carried out to show the benefits of moxibustion in recent years. The current discussions show that moxibustion treatment was an efficient and safe option for the treatment of pain, including arthritis,9 dysmenorrhea,10 low back pain or neck pain,12 and some other disorders. These trials had been shown that moxibustion can significantly relieve pain and improve function in patients. However, the kinds of literature in this field were diversified and had not been systematically classified and sorted out. Therefore, bibliometric analysis was needed to summarize the current research trend and elicit hotspots in this field. These dissertations seek to investigate the use of moxibustion in analgesia aiming to analyze the current status of moxibustion research for pain disease.

Bibliometrics is a quantitative analysis of published academic literature by using mathematical and statistical methods, and it is a statistical analysis and quantitative tool to study publications.13 Based on mathematical and statistical tools, bibliometrics is used to measure established and emerging research areas through co-authorship, co-citation, and co-occurrence analyses in a certain research field.14 CiteSpace software typically falls into bibliometric visualization tools that can visualize and analyze emerging trends and transition patterns in scientific literature widely.15

This study aims to explore the current status of year, countries, journals, research areas, authors, keywords, and explore hot topics and emerging trends in the field of moxibustion for pain treatment over the past 10 years by using bibliometric analysis.

All data in this study were collected from the core collection database for WoS via the Zhejiang Chinese Medical University Library website including Science Citation Index Expanded (SCI-Expanded), Social Sciences Citation Index (SSCI), Arts & Humanities Citation Index (A&HCI) and Emerging Sources Citation Index (ESCI) on April 3, 2022. The search strategy was TS=(moxibustion OR moxa OR Moxabustion) AND TS=(pain* OR nocicep* OR ache* OR analg* OR headache* OR migraine* OR stomach ache* OR abdominal ache* OR toothache* OR neck painweek pain OR back pain OR musculoskeletal pain OR sciatic* OR fibromyalg* OR neuralgi* OR hyperalg* OR radiculalg* OR arthralg* OR causalg* OR earache* OR cancer pain OR osteoarthritis OR arthritis). The publications timespan ranged from 2012 to 2021. A total of 360 records were retrieved in this study. In addition, the countries, categories and language of publications were not restricted. The specific search strategies and results are shown in Table 1.

Table 1 The Topic Search Query

Descriptive statistical analysis, co-occurrence analysis and cluster analysis were executed by using CiteSpace 5.8 and Excel 2016, the former mainly to achieve analysis of journals, cited journals, dual-map of cited journals, countries, institutions, authors, references, and keywords; while the latter was mainly applied to depict the annual publications. The parameters of CiteSpace were set as below: (1) time slicing: from January 2012 to December 2021, per slice represent 1 year; (2) term source: all options were selected; (3) selecting criteria: factor k = 25; (4) pruning: pathfinder, pruning sliced networks and pruning merged network were chosen. In this multivariate, time-sharing, dynamic visualization knowledge graph, each node represented an element. The size of the circle represented the frequency of items and the width of lines served as the connection between items. The large size and warm color of a node implied that it has recently exploded with high frequency. The thick links between nodes meant a strong co-leading relationship. Additionally, the nodes with wide purple around them often represented the literature with higher centrality.

A total of 360 publications were included in this study. As shown in Figure 1, the number of publications increased obviously from 20 in 2012 to 71 in 2021. From 2012 to 2018, the number of publications fluctuated at a low level, with the lowest number of publications being in 2012 (with only 20 publications). However, the number of publications increased rapidly in 2019. Furthermore, the number of publications increased continually is reach 71 from 2019 to 2021. The trend of publications indicated that moxibustion, as a complementary treatment, has received more attention, and more studies have been carried out to observe the efficacy of moxibustion on pain in recent years.

Figure 1 The number of moxibustion therapy for pain treatment publications from 2012 to 2021.

Results of our statistical analysis revealed that the total number of journals that published articles on moxibustion treatment for pain was 97. The top 10 journals of moxibustion therapy for pain treatment are shown in Table 2 and the publishers of these journals were mostly located in the United States or England. Evidence-Based Complementary and Alternative Medicine (Evid-based Compl Alt) was the most productive journal (with 62 publications, 17.22% of 360), followed by Medicine (60, 16.67% of 360), and Journal of Traditional Chinese Medicine (20, 5.56% of 360). Furthermore, Lancet Gastroenterology & Hepatology the journal with the highest impact factor (IF), with an IF of 18.486.

Table 2 Top 10 Journals Related to Moxibustion Therapy for Pain Treatment

The analysis of the co-citation of journals indicated a distribution of significant knowledge sources in a particular field. Cited journal map consists of a total of 430 references (as shown in Figure 2 and Table 3). In terms of centrality, the top 5 journals were Gut, Journal of clinical epidemiology, JAMS Journal of Acupuncture and Meridian Studies, BMC Complementary and Alternative Medicine, and BMC Research Notes, respectively.

Table 3 Cited Journals and Centrality Related to Moxibustion Therapy for Pain Treatment

Figure 2 Cited journal maps related to moxibustion therapy for pain treatment from 2012 to 2021.

A dual-map overlay with citing and cited matrices of journals was generated by using CiteSpace 5.8 software (Figure 3). The left side of the map represents citing journals while the right is cited journals which are linked with four citation paths in this illustration. The green paths illustrate that studies published in medicine, medical, clinical journals tended to cite journals primarily in the domains of Molecular, Biology, Genetics and health, nursing, medicine. The paths colored with an orange showcase that research published in Molecular, Biology, Immunology journals preferred to quote journals mostly in the domains of Molecular, Biology, Genetics and health, nursing, medicine.

Figure 3 A dual-map overlay of journals related to moxibustion therapy for pain treatment from 2012 to 2021.

The distribution of the countries map consists of 24 nodes and 30 links (Figure 4). The 360 references were published by researchers from 24 countries, indicating that 24 countries participated in the study of moxibustion therapy for pain. As a result, China (267) had the most publications, followed by South America (37), Korea (36) and England (13) (Table 4). Considering the country centrality, England (0.83) ranked first among the countries, followed by Germany (0.7) and China (0.48).

Table 4 The Top 5 Publications and Centrality of Countries Related to Moxibustion Therapy for Pain Treatment

Figure 4 A country cooperation map related to moxibustion therapy for pain treatment from 2012 to 2021.

CiteSpace was applied to estimate the 238 institutions that have made significant contributions in this field (Figure 5). Shanghai University of Traditional Chinese Medicine (44) ranked first for publications, followed by Chengdu University of Traditional Chinese Medicine (43), and Jiangxi University of Traditional Chinese Medicine (27). Besides, the top 3 institutions with higher centrality were Chengdu University of Traditional Chinese Medicine, the University of Hong Kong, and Shanghai University of Traditional Chinese Medicine (Table 5). Therefore, based on the publications and centrality, we found that the institutions from China paid more concerned with the research of moxibustion treatment in pain currently, and Shanghai University of Traditional Chinese Medicine and Chengdu University of Traditional Chinese Medicine was the strongest cooperation institutions.

Table 5 The Top 10 Publication and Centrality of Institutions Related to Moxibustion Therapy for Pain Treatment

Figure 5 An institution cooperation map related to moxibustion therapy for pain treatment from 2012 to 2021.

Co-authors map consists of 315 nodes and 418 links using CiteSpace software (Figure 6), indicating that the total eligible publications in this study were published by 315 authors. The map of authors was designed to reveal the most prolific author or co-author, as well as demonstrate the closeness of collaboration among the authors, which could provide information on influential research groups and potential collaborators, and help researchers establish cooperative relationships. The top 3 productive authors were Huangan Wu (19), Jun Xiong (18), Luyi Wu (12) (Table 6). Among them, the most prolific author was Huangan Wu, from the Shanghai University of Traditional Chinese Medicine in China, with 19 articles. In terms of centrality, the top 4 authors were Jun Xiong (0.06), Fanrong Liang (0.06), Guixing Xu (0.05) and Adi Wirawan Tjahjono (0.05). From the network, few links between these top authors suggest an urgent need to strengthen the collaboration between these researchers.

Table 6 The Top 5 Publication and Centrality of Authors Related to Moxibustion Therapy for Pain Treatment

Figure 6 Map of cited author related to moxibustion therapy for pain treatment from 2012 to 2021.

Lin Zhao has published many articles in this field recently, and the content of his articles is comparatively original. One of the studies suggested that moxibustion is an effective and safe approach for pain relief in osteoarthritis of the knee.16 System reviews and meta-analysis had proved the effectiveness of moxibustion therapy; nonetheless, there was still a lack of high-quality articles.17 Those scholars with high attainments in this field could create more cooperation and exchanges so as to complete more high-quality articles and scientific research achievements.

Co-citation implies that two articles appear together in the reference list of a third cited article thus the two articles form a co-citation relationship. Co-citation suggests that the cited literature and corresponding research are related in content, and the literature usually contains high-quality content which has significant influence in a particular field of research. By analyzing the literature with high co-citation frequency and centrality, the knowledge foundation of the subject could be obtained. Moreover, the relationship between literature co-citation is likely to change with time. A total of 403 references were generated from 360 records to analyze cited-references. The top 5 cited-references were shown in Figure 7, Table 7. The study published by Shamseer L in 2015 had the highest co-citation counts, followed by Li A (2016) and Song GM (2016), intending to clarify the clinical effect of moxibustion treatment for Knee Osteoarthritis (KOA) through a systematic Review and Meta-Analysis. The review published by Li A concluded that moxibustion can mitigate the symptoms of KOA to some extent.18 Yang MX conducted a randomized controlled trial to identify the synergy between moxibustion therapy and conventional drug.10 With respect to centrality, the first was the article published in 2013 by Deng HY who reviewed on the mechanism of moxibustion effects, among which the most acceptable view is adjusting the nerve-endocrine-immune network and circulatory system to achieve the effects of preventing and curing diseases.19

Table 7 The Top 5 Frequency and Centrality of Citation Related to Moxibustion Therapy for Pain Treatment

Figure 7 (A) Map of cited references related to moxibustion therapy for pain treatment from 2012 to 2021. (B) The top 10 clusters of cited reference related to moxibustion therapy for pain treatment from 2012 to 2021.

To investigate the clusters of a cited-references, the logarithmic likelihood ratio (LLR) algorithm was used to assess nominal terms extracted from the keyword list of articles to the naming of clusters to explore research models and emerging trends in knowledge systems, and to obtain key information from cited references. Seventy-one clusters were generated with a modularity value of 0.86777, indicating that clustering results were highly reliable (Figure 7B). As the figure showed the silhouette was 0.8785, which demonstrated that the resulting network community structure was significant and our cluster was acceptable concurrently. The top 5 clusters were osteoarthritis, primary osteoporosis, clinical research, knee osteoarthritis and metabolomics. Among these groups, the largest one was osteoarthritis, which consisted of 38 reference articles. Cluster #53 angina pectoris was depicted in most vivid yellow which indicated a new research direction that had recently emerged.

The research trend in this field is often represented by analyzing keywords, the increase in occurrence and citation frequency is considered to predict the research frontier in this field. A keyword co-occurrence network containing 302 notes and 538 links (Figure 8). Acupuncture, pain, randomized controlled trial, moxibustion, and management were the top 5 keywords with the highest frequencies; while meta-analysis, acupuncture treatment, randomized controlled trial, irritable bowel syndrome, and ankylosing spondylitis were the top 5 keywords with the highest centrality (Table 8). Interestingly, randomized controlled trial is of high position both in frequency and centrality. RCT was essential for evaluating the efficiency of a certain therapeutic method, but inadequate reporting and design elicited a high level of concern to formulate proper ethical standards. Hence, developing the Consolidated Standards of Reporting Trial (CONSORT) statement is employed promising to improve the quality of reporting of RCTs.20 As double-blind is difficult to meet in clinical trials, single-blind trials were chosen to deploy. The findings suggested that one possible explanation for relieving the joint swelling and pain symptoms in rheumatoid arthritis patients was that moxibustion restricts inflammatory factor release.21 Another trial delivered the consequence that the effectiveness of moxibustion has been implicated in the quantity of stimulus. Experiments displayed that penetrating stimulation could gain yet more moxibustion sensation in analgesia and enhance the quality of life of patients with migraine without aura.22 Management and prevalence are in the front position in the ranking list of frequency which indicates moxibustion is one of the complemental therapies in prophylaxis and treatment. KOA is the only specific disease in the ranking list that demonstrates a relatively mature research trend in this field. IBS ranks highly in the list of centrality makes us investigate the interconnection between moxibustion therapy and chronic visceral hyperalgesia. Moxibustion has its advantages in treating chronic pain in the spine and joints such as ankylosing spondylitis and arthritis. Additionally, the moxibustion method needs to manipulate by following the specific acupuncture point. As different acupuncture points are selected in studies, more attention should be paid to assessing the therapeutic effect of distinct acupuncture points.

Table 8 Top 10 Keywords Related to Moxibustion Therapy for Pain Treatment

Figure 8 Map of keywords related to moxibustion therapy for pain treatment from 2012 to 2021.

The top 20 keywords with the strongest citation burst from 2012 to 2021 are shown in Figure 9. Systematic review and knee osteoarthritis were ranked at the top, while herpes zoster has burst recently. Research progress of moxibustion treatment of pain can be drawn from the strongest citation bursts of keywords evolution. Suspended moxibustion and spinal cord exerted their influences earlier, while herpes zoster and knee osteoarthritis were lucubrated in 2020 and arouse wide public concern hitherto. Particular attention in this area of research has been given to moxibustion therapy in treating certain pain diseases. These keywords will be further discussed in the following section.

Figure 9 Top 20 keywords with the strongest citation bursts. The red color represents the keyword was cited in high frequency and the green color represents in low frequency.

To the best of our knowledge, this is the first bibliometric study of moxibustion therapy for pain management. The general information concluded from the results is listed as follows: (1) The annual number of publications boosted steadily over the past 10 years and the output was expected to grow swiftly which indicates a promising direction in this research field. (2) The Evid Based Complement Alternat Med and the Gut were the top-cited journals in frequency and centrality. (3) The most prolific country is China, which successfully provided crucial research foundation trends. Given that the other top countries were of poor yield, efforts should be paid to strengthen collaboration between countries to potentiate their output. Shanghai University of Traditional Chinese Medicine and Chengdu University of Traditional Chinese Medicine have profound academic backgrounds, and the institutions can achieve more high-quality results by cooperative closely. (4) Huangan Wu was the most active author with the highest cited frequency. (5) The top cited reference in frequency and centrality was the article published by Shamseer L and Deng HY respectively. (6) Pain disease (eg, arthritis, ankylosing spondylitis, herpes zoster, IBS), research method (eg, RCT), and risk assessment (eg, quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field according to the analysis of the keyword.

The results of co-citation demonstrated the fact that literature usually contains high-quality and strong impacts in this research field. Moreover, it may represent the research foundation of a certain field. The current research type relies on meta-analysis and RCTs, and the content involves mechanism and clinical. One of the frontier research hotpots is osteoarthritis which provides novel perspectives on moxibustion therapy indications. Osteoarthritis is a prevalent pain disease that affects people all over the world. Moxibustion, because of the thermal effect on the local area, often has a therapeutic efficacy to analgesia. Recent research has shown that it directly promotes knee cartilage repair, in the meanwhile regulates the composition of the intestinal flora to prohibit inflammatory factor release.23 Some RCTs have suggested that moxibustion therapy is a safe choice for treatment.9,24,25 However, the top-cited were the standard of meta-analysis, indicating that the number of RCTs in this field is relatively limited and the quality needs to be improved. Therefore, researchers should strengthen the study on efficacy evaluation, to promote the view of moxibustion in the treatment of pain and push forward further research in this field.

Interestingly, as we searched publications related to moxibustion and pain, we found that IBS ranked forward in the list with high centrality as an important research spot. IBS is a functional gastrointestinal (GI) disorder that manifests as abdominal pain and a change in bowel habit.26 The research found abundance and diversity of intestinal microflora in the GI were risks of IBS.27 Alteration of intestinal microbiota activated the immune system to foster the formation of inflammatory cytokines to induce intestinal inflammation. However, a recent study found moxibustion treatment can reverse the changes in microbiota profiles and balance GI function.28 Besides, the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome signaling is considered a medium for regulating gut microbiota and intestinal homeostasis.29 Another research indicated that mild moxibustion can control NLRP6 inflammasome signaling to alleviate inflammation to achieve analgesia.30 These results discussed how moxibustion contributes to pain relief.

Recent emerging trends in moxibustion therapy on pain disease were identified according to the keyword bursts from 2012 to 2021, as follows:

(1) Rheumatoid arthritis (RA): Studies have shown that inhibition of relevant cytokines can reduce joint neovascularization to alleviate pain and dysfunction caused by RA.31 Interestingly, moxibustion can regulate inflammatory cytokines released in RA at the molecular level. Downregulated hypoxia-inducible factor-1/vascular endothelial growth factor level can effectively relieve pain intensity in rheumatoid arthritis.32 In addition, moxibustion may diminish the level of inflammatory factors to improve the symptoms of swelling and pain.21 Further technologies in the specific mechanism of moxibustion to RA are urgently warranted.

(2) KOA: Moxibustion therapy is an efficient intervention without pharmacological and surgical for KOA. Current studies have proved that moxibustion is effective in the treatment of KOA. However, it is notable that the smoke of bursting moxa is harmful to ones health. Therefore, it is necessary to find a moxibustion method with less influence of smoke. The study found that maybe smokeless moxibustion can achieve the same therapeutic effect. This will become a new research direction. One exciting recently discovered is that CO2 laser moxibustion is a device as a convenient and environmental substitution that simulates the traditional moxibustion but without smoke or smell.33 Another trial evaluated the effect of the laser moxibustion device with the thermal effect but no smoke is promising for KOA symptoms.9 More smokeless moxibustion therapies are expected to be developed in the future.

(3) Risk: In recent years, the risk of pain diseases attracted more attention from researchers. In particular, suffering from pain disease could raise the occurrence of diverse physical and psychological problems. The high cost of treatment also increases the burden on society.34 Besides, it has an adverse impact on quality of life and physical function. Thus, much more attention should be paid to being aware of the risks of diseases and focusing on prevention and treatment.

(4) Herpes zoster: Herpes zoster can bring health burdens for people of all ages. Complications usually manifest as pain, fever, and itching. The most common is postherpetic neuralgia, which affects one in five people suffering from this disease.35 Moreover, these uncomfortable feelings caused by herpes zoster bring a heavy economic burden from individuals to society.36 Recently, a systematic review and meta-analysis have shown that moxibustion can alleviate postherpetic neuralgia to some extent, which highlights the great potential of moxibustion therapy.37 This review provides a new perspective on interventions for herpes zoster.

In this review, we discuss current adaptable indications of moxibustion therapy, for instance, AS, arthritis, KOA, RA, herpes zoster, IBS and other pain conditions. Most of them are a class of chronic inflammatory conditions affecting the spine or joints and typically fall into musculoskeletal disease. Additionally, our results provide a novel perspective on the therapeutic efficacy and potential of moxibustion therapy in neuralgia and chronic visceral hyperalgesia. These findings provide future possibilities for moxibustion therapy as a complement and alternative to pain management.

This study has used bibliometrics for the first time to perform a visual analysis of literature related to moxibustion for pain treatment, summarized research status and key research forces in this field, and predicted the research trend. In addition, we have used a variety of methods to analyze data, which is suitable for multi-angle interpretation of conclusions. However, this study has limitations that need to be addressed. This study only analyzed the core collection database for Web of Science, because CiteSpace is currently unable to analyze cited references for other databases. It is anticipated that the improvement of this software will enable the expansion of the selection range for databases in the future.

In conclusion, this study reveals hot spots and frontier issues in the field of moxibustion therapy for pain treatment. The findings presented here are expected to promote the optimization of treatment options.

The following information was supplied regarding data availability: the raw data can be directly obtained from the WoSCC of Thomson Reuters.

Thanks to Prof. Chaomei Chen for opening the use of CiteSpace.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

This study was supported by the key plan of Zhejiang Province Traditional Chinese Medicine Prevention and Treatment of Major Disease of the Health and Family Planning Commission of Zhejiang Province (No. 2018ZY008). The trial sponsor is the Third Affiliated Hospital of Zhejiang Chinese Medicine University (219 Moganshan Road, Xihu District, Hangzhou City, Zhejiang Province 310005, China, +86-571-88393504). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors declare that they have no conflicts of interest in this work.

1. Dahlhamer J, Lucas J, Zelaya C, et al. Prevalence of chronic pain and high-impact chronic pain among adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):10011006. doi:10.15585/mmwr.mm6736a2

2. Ashar YK, Gordon A, Schubiner H, et al. Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: a randomized clinical trial. JAMA Psychiatry. 2022;79(1):1323. doi:10.1001/jamapsychiatry.2021.2669

3. Henschke N, Kamper SJ, Maher CG. The epidemiology and economic consequences of pain. Mayo Clin proc. 2015;90(1):139147. doi:10.1016/j.mayocp.2014.09.010

4. Gao Z, Zhang J, Liu GF, Ji LX. Research trends from 2010 to 2020 for pain treatment with acupuncture: a bibliometric analysis. J Pain Res. 2021;14:941952. doi:10.2147/JPR.S300911

5. Region WHOWP. WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region. Geneva, Switzerland: World Health Organization; 2007.

6. Dubois MY, Chen L. Of low back pain and moxibustion. Pain Med. 2014;15(8):12431244. doi:10.1111/pme.12513

7. Han K, Kim M, Kim EJ, et al. Moxibustion for treating cancer-related fatigue: a multicenter, assessor-blinded, randomized controlled clinical trial. Cancer Med. 2021;10(14):47214733. doi:10.1002/cam4.4020

8. Bao C, Zhang J, Liu J, et al. Moxibustion treatment for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized controlled trial. BMC Complement Altern Med. 2016;16(1):408. doi:10.1186/s12906-016-1386-4

9. Zhao L, Cheng K, Wu F, et al. Effect of laser moxibustion for knee osteoarthritis: a multisite, double-blind randomized controlled trial. J Rheumatol. 2021;48(6):924932. doi:10.3899/jrheum.200217

10. Yang M, Chen X, Bo L, et al. Moxibustion for pain relief in patients with primary dysmenorrhea: a randomized controlled trial. PLoS One. 2017;12(2):e0170952. doi:10.1371/journal.pone.0170952

11. Chiu JH. How does moxibustion possibly work? Evid-Based Complementary Alt Med. 2013;2013:198584. doi:10.1155/2013/198584

12. Yuan QL, Guo TM, Liu L, Sun F, Zhang YG. Traditional Chinese medicine for neck pain and low back pain: a systematic review and meta-analysis. PLoS One. 2015;10(2):e0117146. doi:10.1371/journal.pone.0117146

13. Li R, Sun J, Hu H, et al. Research trends of acupuncture therapy on knee osteoarthritis from 2010 to 2019: a bibliometric analysis. J Pain Res. 2020;13:19011913. doi:10.2147/JPR.S258739

14. Guo J, Pei L, Chen L, et al. Research trends of acupuncture therapy on cancer over the past two decades: a bibliometric analysis. Integr Cancer Ther. 2020;19:1534735420959442. doi:10.1177/1534735420959442

15. Chen C. Searching for intellectual turning points: progressive knowledge domain visualization. Proc Natl Acad Sci U S A. 2004;101 Suppl 1(Suppl 1):53035310. doi:10.1073/pnas.0307513100

16. Zhao L, Cheng K, Wang L, et al. Effectiveness of moxibustion treatment as adjunctive therapy in osteoarthritis of the knee: a randomized, double-blinded, placebo-controlled clinical trial. Arthritis Res Ther. 2014;16(3):R133. doi:10.1186/ar4590

17. Yuan T, Xiong J, Wang X, et al. The effectiveness and safety of moxibustion for treating knee osteoarthritis: a PRISMA compliant systematic review and meta-analysis of randomized controlled trials. Pain Res Manage. 2019;2019:2653792. doi:10.1155/2019/2653792

18. Li A, Wei ZJ, Liu Y, Li B, Guo X, Feng SQ. Moxibustion treatment for knee osteoarthritis: a systematic review and meta-analysis. Medicine. 2016;95(14):e3244. doi:10.1097/MD.0000000000003244

19. Deng H, Shen X. The mechanism of moxibustion: ancient theory and modern research. Evid-Based Complementary Alt Med. 2013;2013:379291. doi:10.1155/2013/379291

20. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134(8):663694. doi:10.7326/0003-4819-134-8-200104170-00012

21. Tao S, Wang X, Liao C, et al. The efficacy of moxibustion on the serum levels of CXCL1 and -EP in patients with rheumatoid arthritis. Pain Res Manage. 2021;2021:7466313. doi:10.1155/2021/7466313

22. Gao L, Xie J, Li X, et al. Effect and safety of penetrating moxibustion in treatment of migraine without aura: a randomized controlled trial. Chin J Integr Med. 2021;27(12):927932. doi:10.1007/s11655-021-3327-4

23. Chen Y, Lv J, Jia Y, et al. Effect of moxibustion on the intestinal flora of rats with knee osteoarthritis induced by monosodium iodoacetate. Evid-Based Complementary Alt Med. 2020;2020:3196427. doi:10.1155/2020/3196427

24. Kang HR, Lee YS, Kim SH, et al. Effectiveness and safety of electrical moxibustion for knee osteoarthritis: a multicenter, randomized, assessor-blinded, parallel-group clinical trial. Complement Ther Med. 2020;53:102523. doi:10.1016/j.ctim.2020.102523

25. Lin L, Cheng K, Tan MT, et al. Comparison of the effects of 10.6-m infrared laser and traditional moxibustion in the treatment of knee osteoarthritis. Lasers Med Sci. 2020;35(4):823832. doi:10.1007/s10103-019-02863-9

26. Ford AC, Sperber AD, Corsetti M, Camilleri M. Irritable bowel syndrome. Lancet. 2020;396(10263):16751688. doi:10.1016/S0140-6736(20)31548-8

27. Joo YE. Alteration of fecal microbiota in patients with postinfectious irritable bowel syndrome. J Neurogastroenterol Motil. 2015;21(1):135137. doi:10.5056/jnm14133

28. Wang X, Qi Q, Wang Y, et al. Gut microbiota was modulated by moxibustion stimulation in rats with irritable bowel syndrome. Chin Med. 2018;13:63. doi:10.1186/s13020-018-0220-y

29. Elinav E, Strowig T, Kau AL, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145(5):745757. doi:10.1016/j.cell.2011.04.022

30. Bao CH, Wang CY, Li GN, et al. Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome. World j Gastroenterol. 2019;25(32):46964714. doi:10.3748/wjg.v25.i32.4696

31. Elshabrawy HA, Chen Z, Volin MV, Ravella S, Virupannavar S, Shahrara S. The pathogenic role of angiogenesis in rheumatoid arthritis. Angiogenesis. 2015;18(4):433448. doi:10.1007/s10456-015-9477-2

32. Gong Y, Yu Z, Wang Y, et al. Effect of moxibustion on HIF-1 and VEGF levels in patients with rheumatoid arthritis. Pain Res Manage. 2019;2019:4705247. doi:10.1155/2019/4705247

33. Guo MH, Zhao L, Wu F, et al. CO(2) laser moxibustion for knee osteoarthritis: study protocol for a multicenter, double-blind, randomized controlled trial. Chin J Integr Med. 2020;26(8):568576. doi:10.1007/s11655-019-2714-6

34. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021;397(10289):20822097. doi:10.1016/S0140-6736(21)00393-7

35. Saguil A, Kane S, Mercado M, Lauters R. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician. 2017;96(10):656663.

36. Johnson RW, Rice AS. Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014;371(16):15261533. doi:10.1056/NEJMcp1403062

37. Wu Q, Hu H, Han D, Gao H. Efficacy and safety of moxibustion for postherpetic neuralgia: a systematic review and meta-analysis. Front Neurol. 2021;12:676525. doi:10.3389/fneur.2021.676525

38. Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647. doi:10.1136/bmj.g7647

39. Song GM, Tian X, Jin YH, et al. Moxibustion is an alternative in treating knee osteoarthritis: the evidence from systematic review and meta-analysis. Medicine. 2016;95(6):e2790. doi:10.1097/MD.0000000000002790

40. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med. 2012;172(19):14441453. doi:10.1001/archinternmed.2012.3654

41. Choi TY, Choi J, Kim KH, Lee MS. Moxibustion for the treatment of osteoarthritis: a systematic review and meta-analysis. Rheumatol Int. 2012;32(10):29692978. doi:10.1007/s00296-012-2367-7

42. Tang Y, Yin HY, Rubini P, Illes P. Acupuncture-induced analgesia: a neurobiological basis in purinergic signaling. Neuroscientist. 2016;22(6):563578. doi:10.1177/1073858416654453

43. Bao CH, Wu LY, Wu HG, et al. Moxibustion inhibits apoptosis and tumor necrosis factor-alpha/tumor necrosis factor receptor 1 in the colonic epithelium of Crohns disease model rats. Dig Dis Sci. 2012;57(9):22862295. doi:10.1007/s10620-012-2161-0

Excerpt from:
Research Trends of Moxibustion Therapy for Pain Treatment Over the Pas | JPR - Dove Medical Press

Q2 2022 Exscientia PLC Earnings Call Aug 19, 2022 (Thomson StreetEvents) -- Edited Transcript of Exscientia PLC earnings conference call or presentation Thursday, August 18, 2022 at 12:30:00pm GMT TEXT version of Transcript ================================================================================ Corporate Participants ================================================================================ * Andrew L. Hopkins Exscientia plc - Founder, CEO & Executive Director * Ben R. Taylor Exscientia plc - CFO, Chief Strategy Officer & Executive Director * David Hallett Exscientia plc - COO * Richard Law Exscientia plc - Chief Business Officer * Sara Sherman Exscientia plc - VP of IR ================================================================================ Conference Call Participants ================================================================================ * Chris Shibutani Goldman Sachs Group, Inc., Research Division - Research Analyst * Michael Leonidovich Ryskin BofA Securities, Research Division - Director in Equity Research & Research Analyst * Peter Richard Lawson Barclays Bank PLC, Research Division - Research Analyst * Vikram Purohit Morgan Stanley, Research Division - Equity Analyst ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Hello, everyone. My name is Chris, and I'll be your conference operator today. At this time, I'd like to welcome everyone to Exscientia's business update call for the second quarter of 2022. (Operator Instructions) At this time, I would like to introduce Sara Sherman, Vice President of Investor Relations. Sara, you may begin. -------------------------------------------------------------------------------- Sara Sherman, Exscientia plc - VP of IR [2] -------------------------------------------------------------------------------- Thank you, operator. A press release and 6-K were issued yesterday after U.S. market closed with our first half and second quarter 2022 financial results and business updates. These documents can be found on our website at http://www.investor.exscientia.ai, along with the presentation for today's webcast. Before we begin, I'd like to remind you that we may make forward-looking statements on our call. These may include statements about our projected growth, revenue, business models, preclinical and clinical results and business performance. Actual results may differ materially from those indicated by these statements. Unless required by law, Exscientia does not undertake any obligation to update these statements regarding the future or to confirm these statements in relation to actual results. On today's call, I'm joined by Andrew Hopkins, Chief Executive Officer; Rich Law, Chief Business Officer; and Ben Taylor, CFO and Chief Strategy Officer. Dave Hallett, Chief Operating Officer; and Garry Pairaudeau, Chief Technology Officer, will also be available for the Q&A session. And with that, I will now turn the call over to Andrew. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [3] -------------------------------------------------------------------------------- Thank you, Sara. In the first half of 2022, we made significant advances across the business to scale our team and operations. We have continued to deliver progress across our collaborations and pipeline, positioning us for long-term growth. A detailed overview of our pipeline progress is included in our press release. We believe the decisive actions we've taken to continuously refine and focus our strategy have put us in a strong position to deliver across our portfolio of drug projects, whilst remaining agile and entrepreneurial in our approach. We are well capitalized with $730 million in cash at the end of the quarter, providing several years runway, which is highly pertinent in today's market. On the operational front, our unique, nearly equal balance of talent between drug discovery scientists and technologists continues to be an area of strength. It's what underlines our ability to combine expert drug and the knowledge with tech scalability. In the first half of this year, we continue to add new talent to our team in key areas of growth from companies, including Dr. Mike Krams as our Chief Quantitative Medicine Officer, whose expertise is invaluable as we begin to plan for clinical development in the coming years. And Professor Charlotte Deane, who joined to lead Biologics AI in January. Charlotte is a renowned leader in the field and was recently awarded an appointment to the most excellent order of a British Empire to lead in the U.K. Research and Innovation's rapid response call for projects addressing issues arising from the pandemic. And also Eileen Jennings-Brown has joined us as our Chief Information Officer from her previous position as Head of Technology at the Wellcome Trust. We've also gone through a period of transformative growth. At the time of our IPO in October 2021, our team was around 200 employees. By the end of June in 2022, we had grown to more than 400 employees at locations across the world, building new areas of expertise and growth for a company, such as our clinical and precision medicine infrastructure. During this time, we've also made considerable progress announcing our historic deal with Sanofi to develop a portfolio of AI, precision entry and medicines. Together, with Sanofi, we have formally accepted 2 programs into the collaboration, 1 in oncology, and the other in immunology and information. We are also exploring the potential role of dozens of additional targets identified using a central biologist AI platform in these therapeutic areas, and we look forward to providing additional updates this year. Beyond small molecules, you may recall that our collaboration with Sanofi includes leveraging our translational platform for biologics. We're pleased to say that we have initiated our first project to help Sanofi select patients for one of the important antibody discovery programs. By leveraging our translational platform for our partners, we aim to potentially increase the probability of success for the patients we are seeking to help. Our journey to achieve automation in drug discovery and development is well underway. We're working towards automating not just design, but also some of the biggest bottlenecks in the design-make-test cycles, such as compound synthesis and molecular profiling. Our state-of-the-art automation suite will become operational next year, and we're excited about the potential for ushering a new era of what's possible in accelerating productivity. And with the announcement of top line data in our A2a program, EXS-21546, one of our first-ever AI design molecules entering the clinical trials, we demonstrated the ability of our AI platform to create novel molecules based upon defined design objectives. We're engaged in ongoing translational work to establish a predictive biomarker to enable targeting patients most likely to benefit from our molecule. This has the potential to unlock the key challenge in effectively treating patients with high adenosine signature cancers. We look forward to showing more details on our progress. We're using simulation guided clinical trial design to plan our clinical trial for EXS-21546, which we're calling [Ignite AI]. Identifying the right patients remains core to our approach. We're also using our translational platform and innovative approach to trial design, as we plan our CDK7 CTA submission by the end of the year. We expect to start a trial in patients in the first half of 2023. Overall, we look forward to nominating additional drug candidates and reporting further pipeline progress in the second half of the year. And now, I want to take a deeper dive into the interplay between our business models and our technology strategy and how we're able to achieve productivity and why we are so confident in our ability to achieve success in the future. In short, the more we do, the more we learn. Exscientia's overarching mission is to create better drugs for patients by applying AI and novel technologies, which allows us to be faster and more scalable from traditional methods. We apply the same tech-enabled strategy to all our programs, wherever we are developing new medicines for our own pipeline or for a partner. A fundamental aspect of what we do is based on the scalability of our technology platform. In previous earnings calls, we described how different aspects of our filing approach to AI-first drug discovery in precision medicine and why we differentiate it. It is not simply how differentiated technology platform for this key to success, but also the opportunity tech scaling gives to a strategic interplay across our drug discovery pipeline between our partnerships and our own internal pipeline. Scalability and systems of a technology company means we can create a different way to balance risks compared to a traditional biotech. In our internal pipeline, our focus hones in on areas where we haven't established expertise and where we believe our precision medicine platform can provide the greatest probabilty of success. Our CFO, Ben Taylor, will provide more details on this in a few minutes. Our partnerships not only generate substantial standalone value, but also have a practical application of allowing us to scale. The more we do, the more platform learns and improves. By applying our tech to do challenges, we're expanding our knowledge base and, more than that, increasing the impact that we can bring to the world. So how does translate into the actual pipeline? Because of our technology capabilities, today, we are able to progress a multitude of discovery programs in our pipeline balanced between internal and partner programs. We have a Phase I asset about to enter Phase Ib/II, 3 programs in IND enabling studies, news that which we expect to announce in the coming months, and the rich pipeline of early drug discovery programs that we've highlighted here. Furthermore, beyond what we have presented here, we have an active program of early stage portfolio of target indication and validation projects. We continue to generate targets on our partners, including Sanofi, as mentioned earlier, and have 2 approved programs moving into design. Focus is critical for us. We have prioritized the results at both areas where we can have the greatest impact on better drug development, translation, and patient selection. This has resulted and decided to de-prioritize a few early stage programs so that both resources can be moved to our core areas where we believe outpatient-based translational platform can be applied to increase the overall probability of success in selecting the right patients. Our message today is one of focus and how we can leverage all our platforms and truly impact the probability of success in the clinic going forward. In previous earnings calls, we have talked about Exscientia's AI-first end-to-end process to drug creation. We originally pioneered AI-driven drug design. But as the business go, we have grown downstream into clinical development and upstream into targeted indication. We have a number of parallel and complementary approaches to generate new projects to our pipeline and our partnerships. New projects can come via our center (inaudible), which applies deep learning to genome scale knowledge grasp to identify connections and predict target disease associations. This technology has been actively used to prioritize targets for validation as part of our collaboration with Sanofi. We can also use our patient tissue translational platform to identify new drug targets. You may recall at the AACR earlier this year, we presented an example of how we discovered ALK as a potential new target for ovarian cancer used in our human tissue precision medicine platform. We are also sourcing new assays, models and targets from outside Exscientia, with programs, such as Xcellomics, where we're seeking to accelerate early-stage research with phenotypic screening of novel disease models with academic labs. I'd like to highlight an example where using our capabilities in just 1 quarter, we were able to identify around 20 novel target hypothesis with high confidence from the initial genome-wide search in a collaboration with one of our partners for an inflammation and immunology indication. This is a nice example of the power of our operations, technology and platform, and we can continue to improve them. We plan to present the deep dive of our experimental and AI driven approaches to targeted implication and validation at a future earnings call. I'm now happy to hand over to Richard Law, our Chief Business Officer, who will walk us through how we think about our platform and business development strategies tied together as evidenced by our news flow. Richard and the business development team are quite prolific and created exceptional value for the company. Richard? -------------------------------------------------------------------------------- Richard Law, Exscientia plc - Chief Business Officer [4] -------------------------------------------------------------------------------- Thank you, Andrew. I'll now take a few minutes to walk through our approach to business development at Exscientia and how this has evolved over time. Since the founding of the company, we've continued to expand our capabilities. And in turn, this has increased the value of partnering with Exscientia over time. Using the combination of AI tech platform and the human tissue platform Andrew mentioned earlier, our approach can validate targets in ways that others can't. Rather than relying on the limitations of the traditional industry-dominant human expertise-led approach to selecting targets for new drug discovery projects, one which is a long and sequential process, but then often relying on a single key academic publication. We are using AI to bring to bear a new level of scale and connectivity to turn publication overload and biological complexity into a data-driven confidence builder on which to base the start of new drug discovery projects. Another area to highlight is how we have integrated advanced molecular dynamics and quantum mechanics into our approach to help us fully utilize and understand the potential for a protein structure, whether it is determined or AI predicted to guide molecular design. Molecular dynamics allows the quality of a structure to be assessed, but also provides a movie-like insight into the target's flexibility instead of just a snapshot. This is just one example. As we continue to build and scale these enhancements then builds our value add, not just for us as we can improve on our efficiency, quality and probability of success, but also for our partners. And so the deal terms, milestones and royalties have reflected this build-out as well. We've seen a shift over the past few years. The more end-to-end, fully externalized drug discovery programs with all of our pharma partners, such as BMS and Sanofi. As we expand our capabilities, so the breadth and value of what we can bring to partners will grow. Going forward, within our partnered programs, our aim is not just to do more. It is to have increasing ownership of the partnered projects within our pipeline, principally by enabling a match of drug to patients in the clinic. As an example, our collaboration with Sanofi includes an option for clinical co-investment with a royalty rate up to 21% on net sales of co-funded projects, without any reduction in milestones for the delivery of the asset by the AI discovery engine. There are several potential ways in which we can deliver value for partners, leveraging our end-to-end process. Our partnerships with pharma are often focused on the ability to design a better molecule from an idea, whether that's for a known or relatively novel target. Normal targets are often the least well understood or studied, but the value may be the highest here and where we can provide differentiated expertise since well-known targets will already be well known by others in the industry. It's a balance, but with a combination of biology AI and patient tissue data, we believe we can break the dogma of novel targets being riskier. We can predict who the patients are going to be, even before we start the discovery project. This is key to altering the probability of success equation in the industry in an end-to-end fashion. For known targets and/or molecules, the platform can assess molecules to select the patients and indications for which they are best suited in a way that others can't, as we are testing against actual patient tissue. Thirdly, we have the potential to match the right drug candidates or combinations to the right subsets of patients with our translational work. This is something Andrew mentioned earlier that we are doing for Sanofi. Consider the number of molecules that may have been pushed to the side, that may have unrealized potential for patients. For instance, certain drugs that successfully treated patients in our EXALT-1 trial that had previously failed in clinical trials for that same indication. As we work with partners, we're often generating a number of high-value potential targets, not all of which will be selected to advance. As the internal pipeline advances, some assets will need to be monetized to manage cash flow, and this will mean finding partners for those molecules that will best shepherd them in the clinic with our help, of course. And while there are many opportunities to add value for our partners, our partners are increasingly tapping the full extent of our capabilities from early target discovery all the way through to eventual patient selection. Put simply, the real potential lies in a reengineered process of drug discovery and development, which is the vision and track record our business development team aims to articulate. That is, how when implemented, alongside the reengineered process, AI can drive a step change in the probability of advancing new precise medicines to exactly the right patients. I'll now turn the call over to Ben to walk us through how we think about scale and impact business development has on our platform. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [5] -------------------------------------------------------------------------------- Thank you, Rich. We are often asked 2 important questions. First, how do we determine if a new target should be developed internally or through partnership? Second, how do we think about the value of a partnership program? In the following section, we'll address those questions from a strategic and economic perspective. Before we talk about our business strategy, it's important to spend a moment on the operational value of scale. Economies of scale certainly can benefit us. But much more importantly, increasing our scale can help us design better medicines. The more pipeline programs we work on, the more data we generate and the more design problems we solve. This data and learning can then feed back into the platform to design better drugs more efficiently in the future. Traditionally, in biotech, developing 2 pipeline programs in parallel requires approximately twice the number of people where CRO services is developing one. However, by using a combination of AI-based technologies and novel processes, we have repeatedly demonstrated exceptional productivity gains on both the time and cost compared to traditional benchmarks, while maintaining a relatively small infrastructure. So for us, scaling is not just about developing a bigger pipeline. It is actually helping us develop a better pipeline. This is exactly why we continue to expand our closed loop operating model from target ID through the clinic. The more aspects of development and data we control, the more robust our system can become. Not only do we already have a broad pipeline, but our capacity allows us to initiate another 5 to 10 programs per year. This means that we can continue to expand both our internal pipeline as well as our partnerships into the foreseeable future. We would expect the majority of new programs to be initiated in the partnership model going forward, with a few focused candidates chosen every year for internal development. Here, we can see the valuation impact of our partnership terms by comparing the net present value received in a partnered program versus the same drug as a wholly owned internal program. The chart shows risk adjusted discounted cash flows over the life of a drug candidate, in this case, at a 10% overall probability of success to reflect a slightly better rate than the industry average of 4%. For the orange wholly owned line, we have used publicly available data to create an example of the average cash flow profile for a drug from discovery through commercialization. The cash flow potential is very high, but requires substantial investment, time and risk. In other words, this is a typical biotech model. And you may recall, we shared the assumptions behind this model last November as well. For the teal partnership line, we have used the general terms of our 15 target Sanofi agreement from earlier this year. That partnership uses a broad range of our capabilities, including our target identification, AI-based design and precision medicine platforms, resulting in per project economics of $343 million in potential milestones as well as royalty rates from the high single digits up to 21%. In this example, we are using a low teens royalty that would be appropriate for the average product described. To sum the wholly owned scenario, it results in about twice the discounted cash flows as a partnership, but that only comes after several years of large investment, with substantial binary risk. By comparison, the partnership is always cash flow positive from a direct cost perspective, which strategically makes up for some of the lower NPV. To be clear, we would always prefer twice the value. However, our capacity allows us the flexibility to do both. We can select a focused group of wholly owned targets where our internal capabilities may improve the probability of success, while still capturing a large portion of the additional pipeline value with lower risk through partnerships. In addition, our partnerships are providing us with an operational benefit by building out and improving the technology platform. Now let's take a step back and look at what our current partnership business means in terms of value. If you run all of our BMS and Sanofi programs through the same NPV analysis, it would equal just under half the NPV as if we were to internally develop those candidates as wholly owned programs. Hopefully, this gives a sense of the importance our partnership business contributes to our long-term business model. On this slide, you can see how the model's net present value changes based on our assumption of overall probability of success. The greater the probability of success in the model, the greater the magnitude of value we may achieve from a wholly owned program as compared to a partnered asset. Importantly, even at 100% probability of success, the wholly owned program is only about 3x the partnered NPV, highlighting the importance of having a combined strategy. What this shows is that if we believe our internal capabilities can significantly increase our probability of success, pursuing a wholly owned strategy becomes more valuable. On the other hand, if we think we can increase the probability of success with the partner's capabilities, the partnership model will become closer to or even surpass the wholly owned value. And so we are thoughtful in evaluating each target on our internal ability to improve probability of success. It needs to not only be a target where our AI design will create a differentiated drug, but we also need to know that our precision medicine platform will guide our clinical development, and we will have the internal expertise to execute and potentially commercialize the program. You can also see why we would invest in better translational systems that enable patient enrichment and improved data-driven clinical trials. Both these investments are directly tied to increasing the probability of success at critical points of development. Our approach also provides us benefits and risk diversification. As I just mentioned, we focus our operations on improving probability of success by targeting the most common points of failure in discovery and development. However, on a very basic level, we target binary valuation risk by having a broad portfolio. We believe that having dozens of pipeline candidates increases our chances of having commercial products. As you've seen from our financial results, our partnership business has brought in over $200 million over the last 18 months. This allows us to continue rapidly expanding our platform and pipeline with substantially less dilutive financing required. Finally, we also believe it is underestimated that many biotech companies have a pipeline based on a single scientific hypothesis. If that hypothesis fails, it may undercut all of the products in the pipeline. At Exscientia, we execute projects across therapeutic areas, target classes and types of small molecules, which provides a high level of scientific risk diversification. Andrew earlier spoke about our strategy in the 2 different pipelines. However, it's important to note that, operationally, these 2 models look very similar until the point of entering the clinic. This has actually provided us substantial flexibility in adjusting our pipeline to fit changes in our long-term goals. We have moved programs from our internal pipeline into partnerships as well as converted partnerships into joint ventures. Our core focus is to successfully launch new medicines, so we will continue to be nimble and rational on how we achieve that. Now we'll take a minute to close with highlights from our financial results. Full results are detailed in our press release and Form 6-K. We ended the quarter with $732 million in cash equivalents and bank deposits. We believe this gives us several years of cash runway and the resources to continue investing in our business expansion and differentiated pipeline. Our cash inflows from collaborations for the 6 months ended June 30, 2022, were $117 million, which included $100 million upfront payment from Sanofi. Importantly, our strategy, which we have just reviewed, creates a potential stream of nondilutive capital inflows, helping maintain a strong balance sheet to fund our business. As an example, our operating cash flow in the first half of 2022 was positive $63 million. It is important to note that we do not expect to be operating cash flow positive for the full year, as we continue to invest in our pipeline and platform to best position ourselves for the future. With that, I'll turn the call back over to Andrew. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [6] -------------------------------------------------------------------------------- Thank you, Ben. 10 years ago, Exscientia was founded by a small team in Dundee, Scotland, nearly all of whom are still with us today. Since that time, we forged our way as a leader using AI-driven approaches to modernize how new medicines are created. We've pushed the field by bringing the first AI-designed molecules to clinical trials, and we were the first to improve clinical outcomes in oncology using AI. We are truly transitioning from rapid growth and scaling to now entering a period focused on stability and execution against our long-term vision. And with that, we'll open up a call for questions and answers. ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) Our first question is from Michael Ryskin with Bank of America. -------------------------------------------------------------------------------- Michael Leonidovich Ryskin, BofA Securities, Research Division - Director in Equity Research & Research Analyst [2] -------------------------------------------------------------------------------- Great. And appreciate the overview. I was just wondering on that -- some of the last points you kind of touched on the ability to execute on the (inaudible) platform across multiple programs. Obviously, with the $700 million cash balance, you're really well positioned for a number of year. So could you give us a little bit more color on your hiring plans, your investment plans, both in R&D and the rest of the organization over the next 6 to 12 months. How should we think about deploying some of that capital? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [3] -------------------------------------------------------------------------------- Excellent. Mike, good to hear from you. Thanks for the question. So Ben and I will actually give an answer to this question. So we're well positioned, actually. We've been through rapid scaling over the past few years. We doubled in size year-on-year for the past 4 years now. And at the time of the IPO, we're around 200 people, and we're just over 400 people at the moment. But we do expect to see -- now we can start to see how now the business starts to sort of stabilize around the capacity, which Ben started to describe in his slides, and the ambition we have then for the partnership business. But at the same time, we do continue to invest in technology areas where, we believe, it actually give us a continuous advantage, both for developing our own molecules and our own programs, particularly focusing now in the areas of precision oncology and also areas where we see that we have the next generation of productivity enhancer is going to come from, where that's from, investments in automation, investments in biologics, designed by AI as well. So we do see that the investments we have put in place are actually allowing us then to grow a company, which we believe actually would create a portfolio of agents, which will be designed with translation biology and precision medicine in mind right from the start, but also in a platform, which we believe actually will continue to be one of the most productive drug discovery engines in the industry. So that's a core sort of areas where our strategic plans for the next years are leading to. But to give you a bit more color on that, I want to introduce Ben actually, who has been -- whose team has been doing a lot of work actually in preparing our plans behind this. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [4] -------------------------------------------------------------------------------- Mike, always great hearing from you. So -- well, I think, what hopefully you picked up from the presentation is both of the business models have a great value proposition. So I think what this really highlights is, no question, we've got the balance sheet capital to make investments. However, what we want to continue doing is make smart investments. So where we start everything is how is this either going to benefit our long-term platform or how can we improve the probability of success on a drug that we're designing. And so that's really where we start. It's not about, hey, we're going to set out and invest x number of dollars this year. It's more of a question of how can we make investments that have a lot of impact to them. If we can come up with a great translational strategy and do a patient enrichment scheme around the clinical trials, where we're really impacting the potential to get to market and get to patients, that's something that we're much more likely to do internally. However, we've got a lot of great partners who come in with their own technologies and viewpoints and capabilities. And sometimes, they have a way to do it, and that should be partnered programs. So I think when we take a step back, what we want to do is make sure that we are always in control of the business. And so we have the flexibility to continue investing, but also to make good business decisions. We never want to be held to outside influences. And so I would expect us to have a continuing balanced business model. And to be honest, I kind of like having a low burn rate. So I don't think we're going to flip that the other way around. -------------------------------------------------------------------------------- Michael Leonidovich Ryskin, BofA Securities, Research Division - Director in Equity Research & Research Analyst [5] -------------------------------------------------------------------------------- Okay. Great. That's helpful. And if I could ask a follow-up on the 21546 Phase Ib to start, could you remind us of any details you provided on sort of the format of that trial? Sort of how many patients are you looking, the duration? When should we expect the next data point there? Just -- and if there are any other -- any other things we should be looking for in the clinic in the next 6 to 12 months? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [6] -------------------------------------------------------------------------------- Excellent. Mike. So yes, we've given further details of the 21546 trial design in the next few months. We're really excited by what Mike Krams, our new Chief Quantitative Medicine Officer has been bringing to the organization and particularly thinking about how we're using simulation driven clinical trial designing that and how that has been integrated then with our work on using a precision medicine platform for thinking about sort of translational biomarkers with that. So we'd be really excited to bring that forward to you in the next few months within it. Just to sort of recap on the timings and how we're thinking about the practicalities of it in the trial, I just want to hand this over to Dave Hallett, our COO. -------------------------------------------------------------------------------- David Hallett, Exscientia plc - COO [7] -------------------------------------------------------------------------------- Yes. Thanks, Andrew. Just to reiterate what Andrew said is that the sort of precise details about kind of study designs for both 21546 and the CDK7 asset will be forthcoming in the second half of the year, so watch out for that news flow. But as Andrew said, I think one of the beauties of kind of Mike Krams joining us who is a world expert in kind of, let's call it, creative kind of clinical trial design, reminding that he was the first person ever to kind of lead an effort to use kind of a Bayesin statistics approach to running clinical trials. So what he's brought to the team, I think, not just for the A2a asset, but other ones is that we're running a lot of simulations, kind of hundreds of simulations, in the last few weeks and months just looking at how best to kind of optimize that forthcoming study, which obviously will be in patients, looking at kind of interactions with kind of standard of care. So I can't give you precise details today about patient numbers, about kind of -- about cancer types, but be patient. That will be forthcoming in the second half of the year. In addition to that, clearly, a key part of that is the work that we're doing with our translational platform at the moment in terms of both kind of drug response biomarkers, but also kind of patient response markets. So yes, that will all be forthcoming and a lot of details during the second half of this year. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [8] -------------------------------------------------------------------------------- And Mike, just to the second part of your question, and I hear the word sort of further catalyst coming through as well, and I just want to sort of open it up to Ben, actually, who's been looking at actually the range of potential events we got flowing down actually over the next few months. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [9] -------------------------------------------------------------------------------- Yes. And I would think about it as 3 different areas where you might see things. One is pipeline, two is operations and three is business development. So on the pipeline front, obviously, we've got a lot of candidates that could be moving forward over the course of the next 6 and 12 months. Certainly, our CDK7 and A2a drugs are looking to start the next phase of clinical trials soon for both of those, and more updates coming on that, as you noted. But we have a number of other pipeline programs that are moving forward both internally, and that have been in-licensed by some of our partners. Obviously, we don't have control over the timing of events for our partners, but we will let you know when that happens. And then in addition, I think, operationally, we're looking at a lot of new platform developments coming on. We actually have a lot of technology development going on internally. I think we've probably got one of the biggest and best technology teams in the industry, and they're being incredibly productive right now. So we'll continue to keep you updated as those things come forward. And then finally, Richard has obviously been busy on business development, and we hope he's not going to coast for the next 12 months, and we'll be very busy as well. -------------------------------------------------------------------------------- Operator [10] -------------------------------------------------------------------------------- The next question is from Vikram Purohit with Morgan Stanley. -------------------------------------------------------------------------------- Vikram Purohit, Morgan Stanley, Research Division - Equity Analyst [11] -------------------------------------------------------------------------------- So my first one is on the A2a program. So I know that we're waiting to see more details about the design of that study over the next couple of months here. But on the simulation guided design principles that you mentioned in the release and throughout the call, is there any more color available on particularly what kinds of design features you may be thinking about adding, how these design principles might impact time lines to initial data and the parameters of data we might initially see? And then lastly, how transferable are some of these design features from the A2a program to other pipeline compounds that you're going to be looking at and that are going to be moving forward in the next 1 to 2 years? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [12] -------------------------------------------------------------------------------- Vikram, good to hear from you, and thanks for the question. That's a great question, actually, and it touches upon one of the reasons why it was so important for us to bring someone with Mike Krams' skill set into the organization because it's fundamentally for us about we want to be as innovative in the clinic as we have been as innovative in developing new technologies in discovery. So the way we're thinking then about sort of computational driven, patient-driven clinical trial design in all these approaches is, as you hinted at, this isn't actually just a technology and approach for the A2a molecule. This is actually a philosophy, which we're looking to apply to all our clinical trial design approaches as we go forward. And we've got a number of other projects right now, which we're also actively working on in thinking about sort of trial design. So what we're looking at then is fundamentally how we cut the goal then of how to identify the correct dose and the correct treatment regime as efficiently as possible in the trial design to do that. So that would be potentially -- so obviously, you could think some of the key parameters, and we'll be trying to do that. So as Dave has just hinted that, these simulations allow us to go not just hundreds, but actually thousands of variations then on trial design to be run. And the simulations then allowed us then to think where we can find sort of a maximum tolerated dose and specific on oncology indications. And also really think about how then we design that trial. So we test in A2a then with standard of care and what are the right sort of indications where all sort of -- if there's a combination of standard of care is best applied. As I said, there'll be more details to come on that trial design, particularly how our trial design sits alongside, how we're thinking about developing and validating translational efficacy biomarkers, which is also key, and that's what we use in our human tissue patient based platform for as well, and actually then bringing those 2 fields together. I actually think it creates an almost unique approach for Exscientia on how we start to think about clinical innovation, and that actually is something we really look forward to telling you about in future earnings calls and talking to you through that. This is about how would we bring out innovation, apply some of the really greatest thinking we've seen in this field starting to emerge. So you don't expect sort of a traditional clinical trial approach from Exscientia. We do want to think about how we bring these 2 leading approaches to adaptive trial design and precision medicine together in how we're thinking about our trials, not just for A2a, but actually for all our programs. -------------------------------------------------------------------------------- Vikram Purohit, Morgan Stanley, Research Division - Equity Analyst [13] -------------------------------------------------------------------------------- Got it. That's helpful. And then a quick follow-up on -- going back to capital deployment and business development. So how does the unwinding of the Bayer partnership and the thought process that went into that mutual decision and then also the lessons learned that you've accumulated through the rest of your partnership that you have ongoing? How does all of that impact your perspective of what future partnerships could and should look like, looking out over the next couple of years? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [14] -------------------------------------------------------------------------------- Good question, Vikram, and it's a good opportunity now to introduce you for the first time on our earnings call to Richard Law, our Chief Business Officer. Richard? -------------------------------------------------------------------------------- Richard Law, Exscientia plc - Chief Business Officer [15] -------------------------------------------------------------------------------- Thanks, Andrew. Thanks, Vikram. Yes, as you heard in the press release, we've sunsetted the collaboration with Bayer. And I think what you've seen is an evolution of the company over the last few years. We're much more end-to-end in what we're doing. But most importantly, we've created a system and a process that is now in place with every other partner of ours, whereby we drive everything. This is really vital to both making the best use of how AI works, but also in how we create value from the platform. So we ended on a high with Bayer. We delivered the lead candidate to the design criteria of the collaboration. And we wish them luck with that in the future. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [16] -------------------------------------------------------------------------------- I'll just add in one thing on that, Vikram. So as far as -- I would expect more in the vein of the BMS and Sanofi type of deals on the partnership side going forward. And obviously, that has a great economic return to us. But what we really think about is we want to be a partner on everything that we do across, at least, through the end of discovery. And our partners often may pick it up in clinical, but it's really got to be something strategic in a partnership before that. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [17] -------------------------------------------------------------------------------- Absolute. And look, in many ways, the reason why we sort of ended on a high with Bayer after getting the first milestone with them was actually to do with real development of how would you apply AI, and that's exactly how we've been building our end-to-end platform. And what we find sort of these older type of deals, which are sort of AI only sort of design deals are not the optimal way, which is why we built out Exscientia now, so we can really control the whole process of how we generate experimental data, how we add on upstream and downstream capabilities of target ID and precision medicine, and integrate all these into a new process. And that's fundamentally the advantage we see, and that's why now all our deal structures, all our partnerships are built that way. -------------------------------------------------------------------------------- Operator [18] -------------------------------------------------------------------------------- The next question is from Chris Shibutani with Goldman Sachs. -------------------------------------------------------------------------------- Chris Shibutani, Goldman Sachs Group, Inc., Research Division - Research Analyst [19] -------------------------------------------------------------------------------- With really a foundational tenet being the company's ability to continuously learn and weave into your efforts that what you're learning, I think when you think about your internal pipeline, I always think about your focus as being on small molecules and in oncology. And yet you made some comments about leveraging this towards biologics with some of your partnerships, et cetera. Can you talk about how you were thinking about this sort of therapeutic and modality focus as far as circling what you think might be priorities from an internal pipeline standpoint? And then I have a follow-up. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [20] -------------------------------------------------------------------------------- Excellent. Thank you, Chris. So yes, we're still developing these new areas. And you can see from some announcement we've made where you might think the direction of travel is going. I mean, in January, we hired Professor Charlotte Deane from Oxford to head up and build our new biologics AI design group. That's obviously a strong signal, and that has been going incredibly well. I'm very pleased to see Charlotte join the company, really apply her talents and also win her MBE actually earlier this year. The other thing as well, of course, is there's some important elements around our precision medicine platform, which we think actually opens up a really interesting possibility in this whole biologics space, which is we've already validated our precision medicine platform using human patient tissue for use in both small molecules and antibodies. And in fact, it's already built into the Sanofi deal. And in fact, we've already started our first precision medicine projects with Sanofi, where, actually, we're bringing in their antibodies discovered by Sanofi into our sort of precision medicine sort of pipeline and is a whole set then of milestone-based success fees then based on how we can help Sanofi select patients. So you'll be hearing more of us in the future, I think, Chris, once we're actually sort of ready for prime time to talk about these new developments. But I think you can start to see things taking shape where we are, it's public knowledge, actively interested in how we can design biologics using AI and, importantly, have already validated how we can use precision medicine downstream to test biologics. And we think those 2 things coming together create something very interesting. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [21] -------------------------------------------------------------------------------- Yes. I think the other really important aspect is we're actually building a very modular system. The way that we do it and how we remodel the process actually allows us to slot things in and out. And so if you think about our 5 areas of capabilities, so we do target ID, we can do the drug design using our AI systems, we do a lot of experimental biology, we do our translational technologies, and we're expanding into the clinic. So if we put another modality into design, for example, that would really just be sliding out the small molecule design and putting in a different modality. But the rest of those modules that I talked about would still function in the exact same way. And so we are designing from the foundation to be able to build and grow our business over time and be very flexible on how we advance medicines to patients. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [22] -------------------------------------------------------------------------------- That's a great point, Ben. It's about engineering that process and how we can bring in new technologies and really get synergies of that new technology across the rest of the platform. Chris, it was another part to your question I just wanted to follow up actually. So today -- sorry, sorry, which was oncology focus, yes. So certainly, we do see that for the internal pipeline. As of today, it is small molecule focused and more and more so now focusing on where we can see we can gain an advantage of increasing our confidence and probability of success in the clinic, where we believe we can build validated and high-confidence translational models. And right now, that's in the area of precision oncology. That's where we believe our precision medicine platform, which we already got the first sort of clinical validation of, is giving us confidence. And our goal then is to align our sort of target validation, therapeutic area strategy towards areas which really align then to the clinic and areas where we believe we have higher confidence and probability of success based on these platforms. -------------------------------------------------------------------------------- Chris Shibutani, Goldman Sachs Group, Inc., Research Division - Research Analyst [23] -------------------------------------------------------------------------------- Right, and that leads exactly to my second question. I guess, there was a discussion earlier about 546. Your other near to approaching the clinic asset 617, the CDK7 inhibitor, I believe, with Apeiron. So I think that is that challenge, doing the preclinical into the clinic transition with confidence and enhancing the probability of success. I suppose a standard question will be what types -- what remains to be seen in order for you to feel that you can transition to the clinics just from a housekeeping standpoint. But what might be the first signs that you can demonstrate clinically that 617 is differentiated? And what do you need to learn in humans to inform the next stages? Or can you already set the clinical path based on your preclinical work alone? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [24] -------------------------------------------------------------------------------- Thanks, Chris. I'm going to open this one up to Dave Hallett, who's been leading the 617 program. -------------------------------------------------------------------------------- David Hallett, Exscientia plc - COO [25] -------------------------------------------------------------------------------- Again, Chris, good to meet you virtually. Really good question. The housekeeping piece, let's deal with that one first. So the regulatory talks, kind of clinical formulation piece, all the kind of the boring but necessary pieces we have to do to get it compound to is the patients. They're nearing kind of successful completion, so that kind of regulated the IMPD piece and the tox package that kind of goes with that molecule is there. So that's why we remain confident about giving guidance about opening the CTA later this year. In terms of differentiation where we go next, the things that we'll update you on kind of during the second half of this year and probably a medical meeting into next, the things we're looking at the moment was the -- particularly for CDK7, what's the kind of optimal dosing regimen to kind of maximize the therapeutic index. So -- and preclinically, we're doing work at the moment looking at different dosing schedules to maximize that. In addition to that, we've released some data, and we'll release some more in the next 6 to 9 months, most likely around -- so I refer back to the AACR poster where we started to kind of get an understanding of both the phenotypic level using our platform, but now looking at more molecular levels. What is kind of -- I'm sorry, referring to the ovarian cancer work that we did. We're now getting an understanding, and we look forward to releasing that data as to why certain subgroups of patients in the ovarian cancer setting, what were the molecular markers that underpinned the differential response to the drug. So I think -- yes, so some of the things we're looking for will be to show differentiation and progress is really -- the early part of the clinical study will really be kind of looking not so much for efficacy, but maximizing the therapeutic index, making sure that we find the right dosing regimen in patients, so that we properly test the mechanism. And then we're just narrowing down at the moment, and we'll release that information in due course, about the specific kind of counter subtypes that we're going to look at. So I can't give you any more precision on that at the moment. But like 21546, Chris, we're pretty close and in very advanced discussions about the kind of clinical trial design. So look forward to sharing that with you and the rest of the world in the second half of the year. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [26] -------------------------------------------------------------------------------- Sorry. Ben is on the line. Wonderful, but you go first. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [27] -------------------------------------------------------------------------------- Okay. I was just going to say, Chris, this goes back to something that is very close to our heart and how we think about operations when you were talking about what can we do before we start the trial. So throughout our company, starting from target ID, all the way through the clinic, we always try and use a data-driven modeling, tech-forward approach to doing things. However, you have to balance that with experimental validation. And so the clinical trials will be no different. We intend to start our clinical trials with a tech-driven thesis that has been backed up by the best experimental data that we can get. However, if you think about the heart of an adaptive trial, for example, and that's just one way to do it, there's different ways to do it. That is actually validating that hypothesis in the clinic. You're using Bayesin statistics to do it much more efficiently on much smaller patient populations, but you're basically validating that hypothesis and then designing that, so that the trial can continue once that's been validated. And so we'll continue to use methods like that, that are familiar to the FDA and that the FDA actually really appreciates. But you have to go through and validate these things in the early-stage trials. I think one of the differences is we can do it a lot earlier than other people would. Most of the time, you see people running Phase I and Phase II trials, doing a post hoc analysis and trying to figure out what the right strategy is. We're able to do it from the beginning with the early design and then factoring that into even the Phase I trials. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [28] -------------------------------------------------------------------------------- And Chris, just one final point I just wanted to add to that, particularly around Ben's point on validation, which is, as well as obviously running trials on our drug assets, we continue to look to clinically validate our precision medicine platform, all those things. So as Ben and Dave said, we get our validation as well alongside the innovative trial design that we've run in into leasing the biomarker that we're developing from our platform. But also we're looking for further clinical validation of our precision medicine platform beyond blood cancers, beyond the EXALT-1 trial. And we are looking to be initiating shortly further sort of studies where we start to think about how to validate our precision medicine platform in its own right in other solid cancers as well. -------------------------------------------------------------------------------- Operator [29] -------------------------------------------------------------------------------- The next question is from Peter Lawson with Barclays. -------------------------------------------------------------------------------- Peter Richard Lawson, Barclays Bank PLC, Research Division - Research Analyst [30] -------------------------------------------------------------------------------- Great. Just kind of dovetailing into Chris' question just on CDK7, just a number of [peer] molecules and whether you've kind of synthesize those and whether -- where you think you could potentially have differentiation based upon whether the structure of those molecules or the way they're kind of targeting. Any details around the CDK7 differentiation would be great. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [31] -------------------------------------------------------------------------------- I think probably just to remind you, refer back to information that was kind of generated and disclosed at the time of the IPO. So in the case of CDK7, differentiation against kind of competition, so because most of the molecules that we're aware of that are in the clinic at the moment, and that we have synthesized the compound itself or patent the examples from those companies. Potency selectivity is something that kind of stands out with our molecule. There are molecules that are a little bit ahead of it in the clinic. But in our hands, those molecules are the less potent against CDK7 or are less selective against the wider [kinase]. And we expect that to have kind of manifested several kind of negatives against our approach in that CDK7 itself is a promising mechanism, but it does come with mechanism-based toxicity. If you then add on kind of other kinase activity, you're going to erode that therapeutic index even further. So we're optimistic that we've designed a molecule that can push the therapeutic index as far as it will go in human studies. I mean, the other balanced properties of the molecules as well, so we kind of factored that over to the design. One of the key aspects is that one of the competitive compounds we looked at, we know for a fact actually that the molecule is -- experimentally is a substrate for a number of key transporters in humans. That itself is likely to kind of cause problems in terms of variation and exposure in humans. And just as importantly, that one of the transporters is actually present in tumors that are overexpressed and polarized, such that it is trying to push drugs out of a tumor rather than in. So I guess, in summary, differentiation from potency, selectivity and balanced properties, allowing us to kind of dose a molecule or really test the CDK mechanism, yes, we are not -- as we go into the clinic, I think doing simulations around dosing regimens to maximize that therapeutic index, again, using data and simulations, as we alluded to, kind of looking -- using kind of simulations as well actually on CDK7 to look at kind of likely effects that will happen together with standard of care. So a very -- a lot of data-driven methodology taking place at this moment, which we look forward to share with you in the next 6 months. -------------------------------------------------------------------------------- Peter Richard Lawson, Barclays Bank PLC, Research Division - Research Analyst [32] -------------------------------------------------------------------------------- And then just around the Bayer collaboration or the termination of the program, just any further details around that? And also I think you mentioned the potential to develop one of those targets. Any details around the target and then potential implications? -------------------------------------------------------------------------------- Richard Law, Exscientia plc - Chief Business Officer [33] -------------------------------------------------------------------------------- Yes, I can speak to that a little bit. So yes, so we successfully delivered the lead on the first target that we worked on with Bayer. We're really happy about that. We looked at several other targets. So we use the central biology AI platform and other elements of our target evaluation. And we decided on one other target to start work on. We also pushed back on several other targets that we felt like the target validation wasn't there for them. So we did start on another target. But essentially, at the point of deciding to exit, we agreed with Bayer that we could get full freedom to operate back on that target. So we'll potentially look to start to work on that, either ourselves or maybe even with another partner. -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [34] -------------------------------------------------------------------------------- And one other thing to add on there, Peter. Just to be clear, this was, in many ways, an economically driven decision. Even though we've got wonderful scalability, it's not infinite. And so we need to be really disciplined managers of how we use our resources. So we showed the NPV analysis during our call for the Sanofi deal in comparison to wholly owned. I won't go into the details on Bayer, but it didn't look as good. And so if we're thinking about where we are going to have our team spending time, we would rather have them spend time on programs where we have better economics. And so you've heard it from several of us already. We had a very nice relationship with Bayer, and we'll do business with them again in the future, certainly. But that deal itself wasn't the right deal for the way that we do business now. -------------------------------------------------------------------------------- Peter Richard Lawson, Barclays Bank PLC, Research Division - Research Analyst [35] -------------------------------------------------------------------------------- Any details around the target that you would develop out of that relationship? -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [36] -------------------------------------------------------------------------------- I'll leave this, a very interesting kind of I&I target, but we -- again, just to kind of -- to link back to kind of one of the key themes of today's presentation is really around what we're looking at the moment is again being very accretive of, okay, what is the validation around that target, how does it fit with our precision medicine, is it a target that we feel, either ourselves or a partner, may have a different kind of pharma partner may have kind of technology that changes a view on a public success. So it's scientifically very interesting, but scientifically interesting only gets you so far. So we're spending a lot of time looking at what kind of what are the right patients for that target, kind of what's the landscape and then figuring out is this one for us to take on internally or one that's actually best within a partnership. -------------------------------------------------------------------------------- Peter Richard Lawson, Barclays Bank PLC, Research Division - Research Analyst [37] -------------------------------------------------------------------------------- And just a final question, I guess, for Ben or Andrew just on the ideas of any bolt-on acquisitions. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [38] -------------------------------------------------------------------------------- Good question, Peter. And Exscientia actually, I thin, has been very successful on how we've carefully acquired and integrated companies to grow from our early days, acquiring connected discovery would help us build our experimental biology capabilities, which then actually allowed us to really truly run in our own projects. That allowed us then to really enable the Celgene deal that we signed because we could also have first new deals of the new type we're running, where we could actually then manage the whole thing, running the experiments to doing a project management. And then, of course, last year when we integrated precision medicine into our platform with the acquisition of Allcyte, which has been an incredible integration into the company. And the team has been absolutely fantastic. It is as if we formed Exscientia together actually, I think, the feeling of team is. And so where we think about it now is how do we then position any sort of new acquisitions into our core strategy. I think, hopefully, what came across today, you can see there's a focused strategy emerging now. One that is -- if you think about the platform, how do we increase productivity continuously and how do we increase our probability of success. And that's why for us, building in precision medicine, using sort of the high content approach was so important. But what was more important was actually the network of biobank samples collected from dozens and dozens of hospitals, and that network is expanding as we speak. So what's important for us now would be to look at any acquisition, sort of think about how does it increase our probability of success, moving forward to the clinic, does it potentially allow us to maybe expand into new indications with a greater degree of probability of success, as we've seen with oncology with our current platform, those are the ways we think about something, actually. Those are ways we try to sort of position it, et cetera. And so that's the way we -- that's the way to think about it, Peter, as we go forward. Ben, anything to add to that? -------------------------------------------------------------------------------- Ben R. Taylor, Exscientia plc - CFO, Chief Strategy Officer & Executive Director [39] -------------------------------------------------------------------------------- Yes. I'd say we're always going to be data driven. We're not a dogmatic team. So we're just looking at it and saying, how -- if we're going to invest anything in an external technology, it's got to exceed our internal ROI capability in that area. And we've got a very productive operating team, so that's a pretty high bar. Typically, that's not going to be something that is a tech standalone. We are more interested in things that can integrate with experimental operations, like how are you making experimental data better, the focus of what would probably be interesting. But again, we've got plenty to do internally. We don't worry about doing M&A as a growth driver. But if we find something that makes a lot of sense, we're not opposed to it either. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [40] -------------------------------------------------------------------------------- Absolutely. So Peter, just to reemphasize what Ben just said. Coming back to our concept of modularity, as we build out new technologies, whether we build them ourselves or whether it's an acquisition, are we getting synergy? Is it truly something that we can see could be plug and play that would also synergize with the rest of the platform, whether it's target identification, drug design, different type sort of modalities, design engines or downstream into sort of precision medicine and into clinical sort of innovation, and that's the way to think about it actually. We don't standalone technologies. We want things that actually really give us synergy. So as we plug something in, we can really see that new modality concept gains from actually the rest of the platform. And I would say, our precision medicine, actually, precision medicine has gained so much more by being part of an end-to-end AI-driven drug discovery engine as well. -------------------------------------------------------------------------------- Operator [41] -------------------------------------------------------------------------------- We have further questions. At this time, I'll turn it over to Andrew Hopkins for any closing remarks. -------------------------------------------------------------------------------- Andrew L. Hopkins, Exscientia plc - Founder, CEO & Executive Director [42] -------------------------------------------------------------------------------- Thank you, Chris. We now have a growing pipeline that is progressing towards and actually into the clinic now. And we aim to be as innovative in the clinic as we've been put into our efforts into developing drug discovery and design, and then start to see that come to fruition and come to life as we advance our pipeline. We believe there are many more firsts and achievements that lie ahead of us. Thank you all for joining us today. And operator, you may now disconnect. -------------------------------------------------------------------------------- Operator [43] -------------------------------------------------------------------------------- Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

Follow this link:
Edited Transcript of EXAI.OQ earnings conference call or presentation 18-Aug-22 12:30pm GMT - Yahoo Finance

PLEASANTON, Calif., Aug. 22, 2022 /PRNewswire/ --Roche (SIX: RO, ROG;OTCQX: RHHBY) and its subsidiary TIB Molbiol have developed a COVID-19 test for researchers that detects and differentiates the latest subvariant of interest BA.2.75. The test specifically targets two of the known unique mutations in BA.2.75, which allows clear differentiation against other notable subvariants.

"Roche is pleased to have developed a test for researchers that provides insights into the epidemiology of BA.2.75, helping to understand its impact on public health," said Cindy Perettie, Head of Molecular Labs at Roche Diagnostics Solutions. "Being able to differentiate emerging variants and understanding their similarities and mutations, can provide a basis for experts to make predictions of their spread and response to treatment strategies."

Since it was first detected in India in May 2022, cases of BA.2.75 have been reported in more than a dozen countries. The BA.2.75 is a subvariant related to the Omicron variant. The subvariant is being monitored by both the World Health Organization as well as the Centers for Disease Control and Prevention.It has not reached the level of a Variant of Concern, but differentiating it from BA.4 and BA.5 allows for improved tracking to understand how it is spreading.

The available research use only test, VirSNiP SARS-CoV-2 Spike 147E 152R, adds to the broad suite of COVID-19 test kits developed by Roche and TIB Molbiol, for instance for the detection of the recent BA.4 and BA.5 subvariants, as well as other mutations present in the Omicron SARS-CoV-2 variant.

Roche and TIB Molbiol's researchers continue to work in collaboration with partners globally to continually screen for new variants and emerging diseases.

About the VirSNiP SARS-CoV-2 Spike 147E 152R

The test specifically targets two of the known unique mutations, K147E and W152R, in BA.2.75, which allows clear differentiation against other notable subvariants. This test is for research use only and is available globally. The VirSNiP SARS-CoV-2 Spike 147E 152R for use on Lightcycler(R) and cobas z480 analyser.

About Roche's response to the COVID-19 pandemic

As a leading healthcare company, we are doing all we can to support countries in their fight against COVID-19 and minimising its impact. That is why we are working with governments, policy makers, healthcare professionals and others to help contain the COVID-19 pandemic and make sure patients continue to receive the tests, treatment and care they need.

The pandemic has profoundly raised awareness of the role diagnostics play in COVID-19 diagnosis, treatment development and disease management. Roche has developed and launched more than 20 COVID-19 diagnostics solutions, including polymerase chain reaction (PCR) and rapid antigen and antibody tests. Our solutions serve the entire diagnostic continuum, from high-throughput laboratories to point-of-care and home self-testing, and cover all currently known variants. To help meet global demand, we have supplied more than 1.5 billion tests for COVID-19 since March 2020.

Roche continues to evaluate its existing therapeutic portfolio and is researching future options to help benefit patients with Covid-19. Our IL-6 inhibitor Actemra/RoActemra (tocilizumab)has been approved forpatients hospitalised with severe COVID-19 in more than 30 countries including the European Union and is authorised for emergency use in the United States. The World Health Organization has prequalified Actemra for use in patients with severe COVID-19, facilitating its availability in low- and middle-income countries. In addition, we have been improving access to Actemra by introducing an international differentiated pricing strategy, providing the medicine at cost for use in low- and middle-income countries and non asserting patents in these regions during the pandemic.

We have also been partnering with Regeneron to jointly develop the antibody combination Ronapreve (casirivimab and imdevimab, known as REGEN-COV in the US). It has been approved in multiple territories including the European Union, Japan, and Switzerland and authorised for emergency or temporary pandemic use in many countries including the US. The antibody combination has been made available to patients in more than 60 countries, across many geographies including low and middle income countries. As the virus continues to evolve, we are constantly monitoring Ronapreve's activity against emerging variants of concern, and will share results with health authorities as soon as possible.

Our utmost goal remains to be a trusted partner who acts with urgency to save and improve the lives of patients with COVID-19 and to reduce its burden on society. For more information please visit our COVID-19 response page.

About Roche

Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world's largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

In recognising our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

For further information please contact:Elizabeth BaxterHead of Communications, Molecular Labs & Roche Diagnostics Solutions Portfolio Centre of Excellence[emailprotected]+1.925.523.8812

Nicole ClarkCommunications Manager, Roche Diagnostics Solution Portfolio Centre of Excellence[emailprotected]+1.317.361.9512

SOURCE Roche

Read the original here:
Roche launches COVID-19 test that detects and differentiates the emerging variant of interest BA.2.75 - PR Newswire

On January 20, 2020, the first case of COVID-19 emerged in the United States. More than 30 months on, the pandemic is still considered ongoing.

COVID-19, whose official name is coronavirus disease 2019, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus). The COVID-19 pandemics continuation and severity are mainly due to the viruss fast mutations and its many variants. As a type of RNA virus, SARS-CoV-2 has a very high mutation rate. This is because the RNA polymerase that replicates the viruss genes doesnt have excellent proofreading skills. However, this actually helps the virus by allowing its variants to find new hosts and escape immunity induced by vaccination or previous in

fection. As a result, during the spreading of the virus, different geographic areas have generated genetically distinct variants.

In June 2021, the World Health Organization (WHO) started using the Greek alphabet to describe variants of interest, which are SARS-CoV-2 virus strains that are considered more dangerous than earlier forms of the virus. These variants are typically considered important due to their increased transmissibility, increased virulence, or the COVID-19 vaccines reduced effectiveness against them.

Prior to the WHO rolling out these rules, researchers around the globe came up with their own lineage naming rules to facilitate their genome sequencing of the virus. As SARS-CoV-2 is a rapidly evolving virus with a high rate of lineage turnover, some Western scientists used the letter A to denote the ancestral type, which is the Wuhan original strain, and the letter B to denote a derived lineage. Many variants of interest, such as alpha, beta, delta, and omicron, belong to lineage B.

The current variants of concern, or more precisely, subvariants (i.e. subsidiary variants) of concern, are BA.4 and BA.5. As of August 13, 2022, BA.5 cases accounted for 88.8 percent of all COVID-19 cases in the United States, followed by BA.4 (5.3 percent) and the latters own newer version BA4.6 (5.1 percent). From the statistics, we can see that BA.5 is more transmissible than BA.4, but so far, scientists havent gained an understanding as to why this is the case, as both subvariants are very similar.

As BA.4 and BA.5 are derived from BA.2, theyre very similar to the latter. According to a preprint study on MedRxiv, the spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2. However, each of these subvariants has its own different mutations from BA.2 in other areas of the virus.

BA.4 and BA.5 are more contagious than any other subvariants of the SARS-CoV-

2 virus. According to a Japanese study, the Re value of BA.4 and BA.5 is 1.2 times higher than that of BA.2. The Re value, also known as the Rt value, is a viruss effective reproduction number, which represents the number of people in a population that can be infected by an individual at any specific time. This number represents a viruss transmissibility. BA.4 and BA.5 are 18.3 times more infectious than BA.2, and are currently the subvariants with the fastest increasing transmission rate.

BA.2 used to be the dominant subvariant around the globe, and BA.4 and BA.5 have rapidly replaced BA.2 in many countries, including the United States, since April 2022.

Furthermore, BA.4 and BA.5 appear to have higher pathogenicity than BA.2.

In a preprinted study of animal models, some Japanese researchers infected some wild-type Syrian hamsters with 105plaque-forming units of BA.4, BA.5, or BA.2 subvariants and performed histopathological analysis. They discovered that inflammation, hemorrhage, congestion, and alveolar damage were significantly higher in the lungs of BA.4 and BA.5-infected hamsters than in BA.2-infected ones. Therefore, BA.4 and BA.5 are more pathogenic than BA.2.

So far, the symptoms of BA.4 and BA.5 appear to be mostly upper-respiratory, including sore throat, running nose, incessant cough, headache, and fatigue, which are similar to the typical Omicron symptoms.

In comparison with the other subvariants, BA.4 and BA.5 are masters at bypassing immunity from a previous infection or vaccination. So people who were formerly infected by other Omicron subvariants can also get re-infected.

As the existing COVID-19 vaccines have been developed based on the original strain. Their protection against Omicron has been significantly reduced, and their protection against BA.4 and BA.5 may be even lower.

In the preprinted Japanese study, by analyzing peripheral blood sera from some convalescents, the researchers discovered that the serum neutralizing antibody titers with BA.4 and BA.5 in those patients who had had two to three doses of COVID-19 vaccines and later had a breakthrough infection by BA.1, were significantly lower than those with BA.2. That is, the combination of full-course vaccination and breakthrough infection cannot protect people from BA.4 or BA.5 infection.

Back on June 30, 2022, the Food and Drug Administration (FDA) warned that the effectiveness of existing COVID-19 vaccines had started to wane against Omicron variants, including BA.4/5. According to the FDAs statement, post-authorization observational studies have shown that effectiveness of primary vaccination wanes over time against certain variants, including Omicron.

Is the immunity gained from a previous COVID-19 natural infection effective against BA.4/5? The answer is: it depends. Although BA.4 and BA.5 subvariants are highly immune-evasive, the immunity acquired from an Omicron infection can still be helpful in protecting people against them. However, if the infection was by a different strain, then the protection offered by the infection-induced immunity may not be great.

The following studies shed some light on this issue.

According to the latest data from the UK Health Security Agency, similar to the pandemic situation in the United States, BA.5 has become the dominant subvariant in the UK, accounting for almost 80 percent of all COVID-19 cases.

The UK Health Security Agency has been carrying out a systematic cohort study (pdf) called the SARS-CoV-2 Immunity and Reinfection EvaluatioN (SIREN).

The participants of this study are more than 44,000 National Health Service healthcare workers from 135 hospitals across the UK. These participants are under active follow-up and undergo asymptomatic SARS-CoV-2 PCR testing every 2 weeks. The cohort had a high seropositivity rate of 30 percent before the second wave hit and is now over 95 percent vaccinated.

The incidence of new infections and reinfections is evaluated in this cohort. Reinfection is defined as a new infection (i.e. PCR positive) 90 days after a prior one.

The graph shows the fortnightly trends of PCR positivity in the SIREN cohort study, and they appear to be consistent with the trends of the alpha, delta, BA.1, BA.2, and other COVID variants. Starting from mid-May 2022, due to the prevalence of BA.4/BA.5, the trend has been going upwards again.

According to the graph, there has been an increase in both primary infection and reinfection rates since May 2022. The increase in primary infection rates indicates that Omicron and its subvariants have significantly enhanced transmission rates, resulting in a large number of infections. The increase in reinfection rates indicates that people who were previously infected can still get infected right now. Therefore, the immunity from natural infection doesnt necessarily offer protection against BA.4 and BA.5. Infection-induced immunitys effectiveness in preventing BA.4/5 infection depends on the strain of the previous infection.

Another preprint study was conducted by a team of researchers from Weill Cornell Medicine-Qatar in Doha. According to the study, young and middle-aged adults who were previously infected with earlier subvariants of Omicron may have substantial protection against BA.4 and BA.5. However, for the people that were infected with a variant that appeared before Omicron, they would not have similar protection against reinfection with BA.4 or BA.5.

This preprint study used the S-gene target failure (SGTF) infections to estimate the effectiveness of previous infections with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants. The SGTF status provides a proxy for BA.4/BA.5 infections.

It was discovered that infection with a pre-Omicron variant prevented reinfection by BA.4 or BA.5 with an effectiveness rate of 28.3 percent, and prevented symptomatic reinfection with an effectiveness rate of 15.1 percent. This is because first, a long time has passed since the prior infection; and second, the virus has mutated a lot since then.

The study also found that a previous Omicron infection prevented reinfection by BA.4 or BA.5 with an effectiveness rate of 79.7 percent, and prevented symptomatic reinfection with an effectiveness rate of 76.1 percent. This is because first, the previous infection is relatively recent; and second, the viral mutations have not been large.

Therefore, regardless of previous COVID-19 infections, it is wise for us to maximize our own anti-viral immunity.

The BA.4 and BA.5 sub-lineages are the most transmissible and immune-evasive strains of the COVID-19 virus to date.What are the differences between them and the other subvariants that have given them their ability to escape immunity?

As aforementioned, BA.4 and BA.5 subvariants have identical spike sequences. In comparison with the BA.1 and BA.2 sub-lineages, they have L452R and F486V mutations and the R493Q reversion in the spike receptor binding domain (RBD), which is likely most targeted by neutralizing antibodies.

The production of neutralizing antibodies can be triggered by infection or vaccination. They can result in lifelong immunity to certain viruses. A neutralizing antibody can stop a pathogen from infecting the body by preventing the molecules on the pathogens surface from entering the human cells. As in the case of all enveloped viruses (i.e. the virus cells are inside a lipid membrane), neutralizing antibodies block the attachment of a SARS-CoV-2 virus to the cell and its entry into the cell to infect it.

Some viruses are able to evade neutralizing antibodies by having regular mutations. As a result, the antibodies can no longer recognize them. The BA.2, BA.4, and BA. 5 subvariants all carry a mutation in amino acid L452 of their spike protein. These L452 mutations facilitate their escape from some antibodies directed to certain regions of the receptor-binding domain, and such mutations have also caused several subvariants to appear.

The F486V mutations found in BA.4/5 also facilitate their escape from certain antibodies, whereas the R493Q reversion mutation restores receptor affinity (i.e. strength of the binding) and the fitness of BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively generating more subvariants that are not only more transmissible but also more evasive to antibodies.

According to Christian Althaus, a computational epidemiologist at the University of Bern, their capacity to infect people who were immune to earlier forms of COVID-19 strains has given rise to the prevalence of the BA.4 and BA.5 substrains.

The COVID-19 pandemic is entering its fourth year. People around the globe are hoping to see the light at the end of the tunnel. Then, will BA.4 and BA.5 subvariants be the last of their kind?

The answer is: no. Its almost certain that the virus will continue to mutate and persist.

According to Eric Topol, professor of molecular medicine at the Scripps Research Institute in California, We know BA.5 is not where this ends, unfortunately. We have further variants to work through for an indeterminate period of time.

Kei Sato, a virologist at the University of Tokyo, also holds the same view. He says, Nobody can say BA.4/5 is the final variant. It is highly probable that additional Omicron variants will emerge.

Already, a new variant, BA.2.75, has emerged and is spreading rapidly in India. Many medical experts believe that its another super-contagious Omicron mutant, and virologists fear that it will fuel a new wave of cases around the world.It has been given the nickname Centaurus by social media users.

So far, BA.2.75 has been detected in over 20 countries, with India being hit the hardest. According to the Indian authorities statistics, BA.2.75 is now behind two thirds of the new COVID-19 cases in India. However, it hasnt dramatically increased the countrys COVID-related hospitalization or death rate.

As the BA.2.75 subvariant is still evolving, it may develop more immune-evading mutations in the coming weeks. Some BA.2.75 sequences also have L452R mutations, which enhance the subvariants ability to re-infect people.

Link:
Will Omicron BA.5 Be the Last of the COVID Variants? - The Epoch Times

Heart failure is a common and devastating disorder for which there is no cure. Many conditions that make it difficult for the heart to pump bloodsuch as dilated cardiomyopathy and arrhythmogenic cardiomyopathycan lead to heart failure, but treatments for patients with heart failure do not take these distinct conditions into account.

Investigators from Harvard Medical School and Brigham and Womens Hospital set out to identify molecules and pathways that may contribute to heart failure, with the aim of informing more effective and personalized treatments.

Get more HMS news here

Using single nucleus RNA sequencing, or snRNAseq, to gain insight into the specific changes that occur in different cell types and cell states, the team made several surprising discoveries.

They found that while there are some shared genetic signatures, others are distinct, providing new candidate targets for therapy and predicting that personalized treatment could improve patient care. Results were published online August 4 in Science.

Our findings hold enormous potential for rethinking how we treat heart failure and point to the importance of understanding its root causes and the mutations that lead to changes that may alter how the heart functions, said co-senior author Christine Seidman, the Thomas W. Smith Professor of Medicine and professor of genetics in the Blavatnik Institute at HMS and director of the Cardiovascular Genetics Center at Brigham and Womens.

This is fundamental research, but it identifies targets that can be experimentally pursued to propel future therapeutics, she said. Our findings also point to the importance of genotyping. Not only does genotyping empower research but it can also lead to better, personalized treatment for patients.

An echocardiogram shows abnormal heart structures and functionnotably enlarged left atria and ventricle and reduced contraction in the ventriclein a patient with dilated cardiomyopathy. Video: Brigham and Womens

Seidman and Jonathan Seidman, the Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics at HMS, collaborated with an international team.

To conduct their study, theSeidmans and colleagues analyzed samples from 18 control and 61 failing human hearts from patients with dilated cardiomyopathy, arrhythmogenic cardiomyopathy, or an unknown cardiomyopathy disease.

The human heart is composed of many different cell types, including cardiomyocytes (beating heart cells), fibroblasts (which help form connective tissue and contribute to scarring), and smooth muscle cells. The team used single nucleus RNA sequencing to look at the genetic readouts from individual cells and determine cellular and molecular changes in each distinct cell type.

From these data, the team identified 10 major cell types and 71 distinct transcriptional states.

They found that in the tissue from patients with dilated or arrhythmogenic cardiomyopathy, cardiomyocytes were depleted while endothelial and immune cells were increased. Overall, fibroblasts did not increase but showed altered activity.

Analyses of multiple hearts with mutations in certain disease genesincluding TTN, PKP2, and LMNAuncovered molecular and cellular differences as well as some shared responses.

More here:
Many Paths to Failure | Harvard Medical School - Harvard Medical School

In this micrograph, a human macrophage (a type of immune cell) is shown after reduction of the gene DNMT3A. The large green structure is the cells nucleus; red indicates the presence of cytoplasmic protein. The small green dots represent mitochondrial DNA that has escaped from the nucleus into the cytoplasm, inducing an inflammatory response.

Mitochondria are organelles found within most cells, best known for generating the chemical energy required to power cellular functions. Increasingly, however, researchers are discovering how mitochondrial function and dysfunction play critical roles in numerous diseases, and even aging.

In a new study published in the August 4, 2022 online issue of Immunity, scientists at University of California San Diego School of Medicine and Salk Institute for Biological Studies report a surprising link between mitochondria, inflammation and DNMT3A and TET2, a pair of genes that normally help regulate blood cell growth, but when mutated, are associated with an increased risk of atherosclerosis.

We found that the genes DNMT3A and TET2, in addition to their normal job of altering chemical tags to regulate DNA, directly activate expression of a gene involved in mitochondrial inflammatory pathways, which hints as a new molecular target for atherosclerosis therapeutics, said Gerald Shadel, PhD, co-senior study author and director of the San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging at Salk Institute. They also interact with mitochondrial inflammatory pathways, which hints at a new molecular target for atherosclerosis therapeutics.

While studying the roles of DNMT3A and TET2 mutations in clonal hematopoiesis, which happens when stem cells begin making new blood cells with the same genetic mutation, co-senior study author Christopher Glass, MD, PhD, professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, and colleagues noted that abnormal inflammatory signaling related to DNMT3A and TET2 deficiency in blood cells played a major role in the inflammation response that promotes development of atherosclerosis.

Christopher Glass, MD, PhD, is professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.

But the question remained how DNMT3A and TET2 genes were involved in inflammation and atherosclerosis the buildup of fatty plaques in arteries and the primary underlying cause of cardiovascular disease. It is estimated approximately half of Americans between the ages of 45 and 84 have atherosclerosis, which is the single leading cause of death in the United States and westernized nations.

The problem was we couldnt work out how DNMT3A and TET2 were involved because the proteins they code seemingly do opposite things regarding DNA regulation, said Glass. Their antagonistic activity led us to believe there may be other mechanisms at play, which prompted us to take a different approach and contact Shadel, who had uncovered the same inflammatory pathway years earlier while examining responses to mitochondrial DNA stress.

Inside mitochondria resides a unique subset of the cells DNA that must be organized and condensed correctly to sustain normal function. Shadels team had previously investigated the effects of mitochondrial DNA stress by removing TFAM, a gene that helps ensure mitochondrial DNA is packaged correctly.

Shadel and colleagues determined that when TFAM levels are reduced, mitochondrial DNA is expelled from mitochondria into the cells interior, setting off the same molecular alarms that alert cells to a bacterial or viral invader and trigger a defensive molecular pathway that prompts an inflammatory response.

Gerald Shadel, PhD, is director of the San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging at Salk Institute for Biological Studies.

Glass and Shadels labs worked together to better understand why DNMT3A and TET2 mutations led to inflammatory responses similar to those observed during mitochondrial DNA stress. The teams applied genetic engineering tools and cell imaging to examine cells from people with normal cells, those with loss of function mutations in DNMT3A or TET2 expression and those with atherosclerosis.

They discovered that experimentally reducing the expression of DNMT3A or TET2 in normal blood cells produced similar results to blood cells that had loss of function mutations and to blood cells from atherosclerosis patients. In all three cases, there was an increased inflammatory response.

They also observed that low levels of DNMT3A and TET2 expression in blood cells led to reduced TFAM expression, which in turn led to abnormal mitochondria DNA packaging, instigating inflammation due to released mitochondrial DNA.

We discovered that DNMT3A and TET2 mutations prevent their ability to bind and activate the TFAM gene, said first author Isidoro Cobo, PhD, a postdoctoral scholar in Glass lab. Missing or reducing this binding activity leads to mitochondrial DNA release and an overactive mitochondrial inflammation response. We believe this may exacerbate plaque buildup in atherosclerosis.

Shadel said the findings broaden and deepen understanding of mitochondrial function and their role in disease.

Its very exciting to see our discovery on TFAM depletion causing mitochondrial DNA stress and inflammation now have direct relevance for a disease like atherosclerosis, said Shadel. Ever since we revealed this pathway, there has been an explosion of interest in mitochondria being involved in inflammation and many reports linking mitochondrial DNA release to other clinical contexts.

Therapeutics that target inflammation signaling pathways already exist for many other diseases. Glass and Shadel believe that blocking pathways that exacerbate atherosclerosis in patients with TET2A and DNMT3A mutations could form the basis for new treatments.

Co-authors include: Tiffany N. Tanaka, Addison Lana, Calvin Yeang, Claudia Han, Johannes Schlachetki, Jean Challcombe, Bthany R. Fixen, Rick Z. Li, Hannah Fields, Randy G. Tsai and Rafael Behar, all at UC San Diego; Kailash Chandra Mangalhara, Salk; Mashito Sakai, UC San Diego and Nippon Medical School, Japan; Michael Mokry, Wilhelmina Childrens Hospital, the Netherlands; and Koen Prange and Menno Winther, University of Amsterdam, the Netherlands.

This research was supported, in part, by the Leducq Transatlantic Network Grant (16CVD01), the National Institutes of Health (P01 HL147835, 1KL2TR001444, R01 AR069876 and NS047101), the European Molecular Biology Organization (ALTF 960-2018), ZonMw (09120011910025) and the Netherlands Heart Foundation (GENIUSII and 2019B016) and Confocal Microscopy Core (NSO47101).

Read the original:
Mitochondrial DNA Mutations Linked to Heart Disease Risk - University of California San Diego

The University of California, Davis, reached a major milestone attracting $1.07 billion in external research funding in the fiscal year 2021-22, up $102.9 million from the previous record set last year. In doing so, UC Davis joins an exclusive group of fewer than 20 public universities in the nation surpassing $1 billion in research funding.

The awards lend support to a wide range of research areas including advancing public health and medicine, developing new technologies in food, agriculture and the environment, empowering the underserved and enabling a more resilient society.

This new record for research award funding marks a historic moment for UC Davis, said Chancellor Gary S. May. More than ever, our university is on a mission to address some of the worlds greatest challenges, from how we feed the world to the health of all living beings. This milestone shows clearly how UC Davis research is being sought more than ever, by both the public and private sector, and across numerous fields. Im confident this kind of global impact from UC Davis will only continue to grow.

A primary contributor to this years growth came from funding within the College of Agricultural and Environmental Sciences, up by $72 million from the previous year for a total of $225 million. The School of Medicine also noticed a large increase, adding $29 million for a total of $396 million. The School of Veterinary Medicine ($89 million), College of Engineering ($79 million) and College of Biological Sciences ($68 million) rounded out the top five.

The federal government remained the largest provider of funding at $499 million, although down by $15 million from last year. The second leading source was the state of California at $210 million, up by $46 million from the previous year. Funding from industry made up the third highest source, totaling $104 million. Substantial increases also came from charities (up $26 million) and other UC programs (up $29 million).

As the funding for research grows, so does the impact that UC Davis extends around the world, said Prasant Mohapatra, vice chancellor for research at UC Davis. This years grand accomplishment of surpassing $1 billion in research funding will translate into tomorrows discoveries, insight and products that offer a brighter future for our global community.

An event to celebrate the achievement and showcase some of the exciting research discoveries and emerging technologies is planned for this fall. You can sign up to register for the event here.

The largest award, $53.4 million from the USDA Food and Nutrition Service, went to Kamaljeet Khaira, director of the University of California CalFresh Nutrition Education Program (UC CalFresh) to help reduce the chronic rate of obesity and encourage the awareness of healthy foods and increased physical activity among low-income individuals.

The goal of the GEMINI: GxExM Innovation in Intelligence for climate adaptation project is to use 3D modeling, artificial intelligence and crop genetics to develop new technologies to improve and accelerate breeding pipelines for common bean, cowpea and sorghum, which are key crops for food and income for smallholder farmers in sub-Saharan Africa. The project is co-led by Christine Diepenbrock and Brian Bailey, assistant professors in the Department of Plant Sciences, and Mason Earles, assistant professor in the Department of Biological and Agricultural Engineering, and funded by the Bill & Melinda Gates Foundation.

This research project aims to integrate molecular and cellular physiology measurements on single neurons in order to identify how disease-causing genetic mutations alter neuron behaviors. Gerald Quon, an assistant professor in the Department of Molecular and Cellular Biology and the Genome Center, is leading the project that is funded by the National Institutes of Health (NIH).

The goal of the alternative COVID-19 antigen production project is to explore the viability of a range of biomanufacturing technologies to produce antigens using six different systems: two plants, and cultured mammalian, bacterial, yeast and filamentous fungal cells. The two-year project is led by Karen McDonald, a professor in the Department of Chemical Engineering, and funded by the National Institute of Standards and Technologies (NIST) through the Bioindustrial Manufacturing and Design Ecosystem (BioMADE),

The psychedelics research project led by David Olson, an associate professor in the departments of Chemistry and Biochemistry and Molecular Medicine, plans to screen hundreds of compounds to discover new, nonhallucinogenic treatments for substance use disorders. Funded by the National Institute on Drug Abuse, part of the National Institutes of Health, the study will help us understand the basic mechanisms by which these compounds impact addiction and may help development of more effective and better tolerated treatments.

The two projects from UC Davis Continuing and Professional Education Human Services are focused on supporting the delivery of training and workforce development services for public child welfare agencies and community-based organizations providing intensive services to vulnerable children, youth and families throughout California. Funded by the California Department of Social Services, the programs include instruction and development of new courses and training programs to meet evolving needs of the states child- and family-serving agencies. The projects are led by program directors Alison Book and Nancy Hafer.

The Blackstone Charitable Foundation project supports the creation of entrepreneurs and innovators under the name "Blackstone LaunchPad with a focus on entrepreneurial skill-building so students can succeed in any career they choose. The UC Davis Blackstone LaunchPad makes progress towards specific milestones of increasing cumulative UC Davis student participation each year to support their skills in moving from ideas to growth to ultimately positive impact through a variety of on- and off-campus activities. The project is led by Andrew Hargadon, a professor and Soderquist Chair in Entrepreneurship in the Graduate School of Management (administered by the Mike and Renee Child Institute for Innovation and Entrepreneurship) and sponsored by Hanumantha Unnava, dean of the school.

The project titled Examining how teacher-student interactions within mathematics and literacy instructional contexts relate to the developmental and academic outcomes of early elementary students with autism proposes to bridge the gap between autism research and general education practices. The project is led by Nicole Sparapani, an associate professor in the School of Education and the MIND Institute, along with co-principal investigators Professor Peter Mundy and Nancy Tseng, lecturer in the UC Davis School of Education. Funded by the Institute of Education Sciences, the team will explore how general education teachers can use inclusive math and literacy instructional practices to support learners with autism in their kindergarten to third grade general education classrooms in large, diverse public school districts in Northern California.

The goal of this project from the School of Law is to provide legal services without charge to indigent persons, particularly client groups that have traditionally lacked significant legal representation including migrants, survivors of domestic violence and individuals whose civil rights have been violated. It is led by Gabriel Chin, professor of law and director of Clinical Legal Education, and funded by the State Bar of California.

This research project will examine hospital-to-home transitions for older adult couples who are managing heart failure. The ultimate goal is to develop interventions to support better symptom response and management during these transitions. The project is led by Julie T. Bidwell, an assistant professor in the Family Caregiving Institute at the Betty Irene Moore School of Nursing, and supported by the National Institutes of Health and National Institute of Nursing Research.

This project aims to improve breast cancer, heart health and Alzheimers disease care for women. The Krueger v. Wyeth Settlement Funds award will enable UC Davis Health researchers to study health disparities and advance projects focused on women of color and those in underserved communities. These women are traditionally underrepresented in research and have unique disease risks. As program director, Angela Haczku, a professor of medicine and associate dean of research at the School of Medicine, is assisting principal investigators Professor Luis Carvajal-Carmona, Professor Diana Miglioretti, Professor Amparo Villablanca and Professor Rachel Whitmer, School of Medicine leading the work in the four major projects of this collaborative research award.

Through a project funded by the National Science Foundation titled Impacts of rapid landscape change and biodiversity on virus host specificity, the researchers plan to investigate emerging and re-emerging viruses in transitional ecosystems where landscape change is most likely to influence disease transmission from wildlife to humans. The project is led by Christine Johnson, professor of epidemiology and ecosystem health in the UC Davis School of Veterinary Medicine and Assistant Researcher Tierra Smiley Evans (EpiCenter for Disease Dynamics, One Health Institute), Professor Lark Coffey (Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine), Rebekah Kading (Colorado State University), Mike Boots (UC Berkeley), and Ohnmar Aung and Pyae Phyo Aung (Nature Conservation Society - Myanmar).

Interdisciplinary research conducted by Organized Research Units, Special Research Programs, and IMPACT Centerswithin the Office of Research continued to attract significant funding at $113 million, up 19% from last year.** These joint efforts often focus on addressing complex, large-scale challenges that require expertise from many perspectives. Notable examples include:

The UC Davis Energy and Efficiency Institute, as a sub-awardee from Lawrence Berkeley Laboratory, will establish the California Flexible Load Research and Deployment Hub to conduct electricity sector applied research and development and technology demonstration and deployment projects. The goal of the project is to reduce dependence on fossil generation, firm up renewable resources to help California achieve its renewable generation and decarbonization goals. The principal investigator at UC Davis is Professor John Kissock, Department of Mechanical and Aerospace Engineering. The project is funded by the California Energy Commission.

The goal ofthis projectis to identify treatments and develop therapeutics to stop Alzheimers disease from causing irreversible damage to the brain.John H Morrison, professor in the Department of Neurology and director of the California National Primate Research Center, and his team are developing nonhuman primate models of Alzheimers disease that could explain the biochemical and cellular basis of neurodegeneration associated with the disease, and provide new therapeutic targets.This project was funded through theNational Institute on Aging(NIA).

This cooperative effort between the National Park Service and the Air Quality Research Center(AQRC)at UC Davis will analyze data and develop new methods and approaches to enhance the quality and scope of monitoringparticulate matter andvisibility in national parks, wilderness areas, wildlife refuges and other protected areas designated by Congress. The project is an enhancement to the Interagency Monitoring of Protected Visual Environments (IMPROVE) network,which is operated by the AQRC at UC Davis,and is led by AnnM.Dillner, associate director of analytical research, with funding from theU.S. National Park Service and support from the U.S. Environmental Protection Agency.

Note: Reports are based on the principal investigators home school or college. Where funds are awarded up-front to cover several years, the money is counted in the first year the award was received. Incrementally funded awards are counted as authorized in each year.

*Project funding allocated in fiscal year 2019, but active in fiscal year 2022.

**Interdisciplinary totals reported by principal investigators administrative unit

See the rest here:
UC Davis Sets a New Record, Surpasses $1 Billion in Research Funding - University of California, Davis

Yale University, New Haven, CT, USA

Gita A. Pathak&Renato Polimanti

Institute for Molecular Medicine Finland (FIMM), Univerisity of Helsinki, Helsinki, Finland

Juha Karjalainen,Mark Daly,Andrea Ganna&Mark J. Daly

Broad Institute of MIT and Harvard, Cambridge, MA, USA

Christine Stevens,Mark Daly,Andrea Ganna,Masahiro Kanai,Rachel G. Liao,Amy Trankiem,Mary K. Balaconis,Huy Nguyen,Matthew Solomonson,Kumar Veerapen,Samuli Ripatti,Lindo Nkambul,Mark J. Daly,Sam Bryant&Vijay G. Sankaran

Massachusetts General Hospital, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Benjamin M. Neale

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

Mark Daly,Andrea Ganna,Konrad J. Karczewski,Alicia R. Martin,Elizabeth G. Atkinson,Masahiro Kanai,Kristin Tsuo,Nikolas Baya,Patrick Turley,Rahul Gupta,Raymond K. Walters,Duncan S. Palmer,Gopal Sarma,Matthew Solomonson,Nathan Cheng,Wenhan Lu,Claire Churchhouse,Jacqueline I. Goldstein,Daniel King,Wei Zhou,Cotton Seed,Mark J. Daly,Benjamin M. Neale,Hilary Finucane,F. Kyle Satterstrom&Sam Bryant

Icahn School of Medicine at Mount Sinai, New York, NY, USA

Shea J. Andrews,Laura G. Sloofman,Stuart C. Sealfon,Clive Hoggart&Slayton J. Underwood

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

Mattia Cordioli,Matti Pirinen,Kati Donner,Katja Kivinen,Aarno Palotie&Mari Kaunisto

Icahn School of Medicine at Mount Sinai, Genetics and Genomic Sciences, York City, NY, USA

Nadia Harerimana

Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland

Karolina Chwialkowska

University of Michigan, Ann Arbor, MI, USA

Brooke Wolford

Ancestry, Lehi, UT, USA

Genevieve Roberts,Danny Park,Catherine A. Ball,Marie Coignet,Shannon McCurdy,Spencer Knight,Raghavendran Partha,Brooke Rhead,Miao Zhang,Nathan Berkowitz,Michael Gaddis,Keith Noto,Luong Ruiz,Milos Pavlovic,Eurie L. Hong,Kristin Rand,Ahna Girshick,Harendra Guturu&Asher Haug Baltzell

Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland

Mari E. K. Niemi&Sara Pigazzini

University of Liege, GIGA-Institute, Lige, Belgium

Souad Rahmouni,Michel Georges&Yasmine Belhaj

CHC Mont-Lgia, Lige, Belgium

Julien Guntz&Sabine Claassen

5BHUL (Lige Biobank), CHU of Lige, Lige, Belgium

Yves Beguin&Stphanie Gofflot

Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

Mattia Cordioli

Analytic & Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

Lindokuhle Nkambule,Lindokuhle Nkambul,Lindokuhle Nkambule&Lindo Nkambul

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Lindokuhle Nkambule

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Lindokuhle Nkambule,Konrad J. Karczewski,Alicia R. Martin,Elizabeth G. Atkinson,Masahiro Kanai,Kristin Tsuo,Nikolas Baya,Patrick Turley,Rahul Gupta,Raymond K. Walters,Duncan S. Palmer,Gopal Sarma,Matthew Solomonson,Nathan Cheng,Wenhan Lu,Claire Churchhouse,Jacqueline I. Goldstein,Daniel King,Wei Zhou,Cotton Seed,Benjamin M. Neale,Hilary Finucane,F. Kyle Satterstrom,Sam Bryant&Caroline Cusick

CHU of Liege, Lige, Belgium

Michel Moutschen,Benoit Misset,Gilles Darcis,Julien Guiot,Samira Azarzar,Olivier Malaise,Pascale Huynen,Christelle Meuris,Marie Thys,Jessica Jacques,Philippe Lonard,Frederic Frippiat,Jean-Baptiste Giot,Anne-Sophie Sauvage,Christian Von Frenckell&Bernard Lambermont

University of Liege, Lige, Belgium

Michel Moutschen,Benoit Misset,Gilles Darcis,Julien Guiot&Samira Azarzar

Department of Human Genetics, McGill University, Montreal, Quebec, Canada

Tomoko Nakanishi

Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

Tomoko Nakanishi,David R. Morrison,J. Brent Richards,Guillaume Butler-Laporte,Vincenzo Forgetta,Biswarup Ghosh,Laetitia Laurent,Danielle Henry,Tala Abdullah,Olumide Adeleye,Noor Mamlouk,Nofar Kimchi,Zaman Afrasiabi,Nardin Rezk,Branka Vulesevic,Meriem Bouab,Charlotte Guzman,Louis Petitjean,Chris Tselios,Xiaoqing Xue,Jonathan Afilalo&Darin Adra

Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Tomoko Nakanishi

Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan

Tomoko Nakanishi

McGill Genome Centre and Department of Human Genetics, McGill University, Montreal, Quebec, Canada

Vincent Mooser,Rui Li,Alexandre Belisle,Pierre Lepage,Jiannis Ragoussis,Daniel Auld&G. Mark Lathrop

Department of Human Genetics, Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

J. Brent Richards

Department of Twin Research, Kings College London, London, UK

J. Brent Richards

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montral, Qubec, Canada

Guillaume Butler-Laporte

Department of Emergency Medicine, McGill University, Montreal, Quebec, Canada

Marc Afilalo

Emergency Department, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

Marc Afilalo

McGill AIDS Centre, Department of Microbiology and Immunology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

Maureen Oliveira

McGill Centre for Viral Diseases, Lady Davis Institute, Department of Infectious Disease, Jewish General Hospital, Montreal, Quebec, Canada

Bluma Brenner

Research Centre of the Centre Hospitalier de lUniversit de Montral, Montreal, Canada

Nathalie Brassard

Department of Medicine, Research Centre of the Centre Hospitalier de lUniversit de Montral, Montreal, Canada

Madeleine Durand

Department of Medicine, Universit de Montral, Montreal, Canada

Madeleine Durand,Michal Chass&Daniel E. Kaufmann

Department of Medicine and Human Genetics, McGill University, Montreal, Quebec, Canada

Erwin Schurr

Department of Intensive Care, Research Centre of the Centre Hospitalier de lUniversit de Montral, Montreal, Quebec, Canada

Michal Chass

Division of Infectious Diseases, Research Centre of the Centre Hospitalier de lUniversit de Montral, Montreal, Quebec, Canada

Daniel E. Kaufmann

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK

Caroline Hayward,Anne Richmond&J. Kenneth Baillie

Center for Applied Genomics, Childrens Hospital of Philadelphia, Philadelphia, PA, USA

Joseph T. Glessner,Hakon Hakonarson&Xiao Chang

Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Joseph T. Glessner&Hakon Hakonarson

Vanderbilt University Medical Center, Nashville, TN, USA

Douglas M. Shaw,Jennifer Below,Hannah Polikowski,Petty E. Lauren,Hung-Hsin Chen,Zhu Wanying,Lea Davis&V. Eric Kerchberger

Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK

Archie Campbell,David J. Porteous&Chloe Fawns-Ritchie

Usher Institute, University of Edinburgh, Nine, Edinburgh Bioquarter, Edinburgh, UK

Archie Campbell

University of Texas Health, Houston, TX, USA

Marcela Morris&Joseph B. McCormick

Department of Psychology, University of Edinburgh, Edinburgh, UK

Chloe Fawns-Ritchie&Chloe Fawns-Ritchie

University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Kari North

Center for Applied Genomics, The Childrens Hospital of Philadelphia, Philadelphia, PA, USA

Xiao Chang,Joseph R. Glessner&Hakon Hakonarson

Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Joseph R. Glessner

See original here:
A first update on mapping the human genetic architecture of COVID-19 - Nature.com