Evgenia Shishkova, assistant staff scientist from the Coon Lab. Credit: Morgridge Institute for Research

While most COVID-19 cases are asymptomatic or mild, severe complications associated with acute respiratory distress have led to more than one million deaths worldwide in just several months.

Researchers from the Morgridge Institute for Research, the University of Wisconsin-Madison, and Albany Medical College sought to better understand the molecular factors that drive the severity of COVID-19, and offer insight into treatment options for those with advanced disease.

The collaborative study published online in Cell Systems identified more than 200 molecular features that strongly correlate with COVID-19 severity.

To my knowledge, this the largest outcome study, says Dr. Ariel Jaitovich, a pulmonary and critical care physician at Albany Medical Center. I know that there are some large studies focused on the diagnostics (infected versus non-infected). We have a large group of just COVID patients, but with a very granular difference in terms of severitythat is something that I hadnt seen.

The team analyzed 102 blood samples from patients diagnosed with COVID-19, and 26 samples from patients with acute respiratory distress syndrome (ARDS) but negative for COVID-19 as controls.

I felt like we had a unique opportunity with Ariels cohort that he had recruited. It was very early in the COVID epidemic here in the United States, so he was really out on the forefront of getting these types of samples from the clinic, says Josh Coon, Morgridge metabolism investigator and professor of biomolecular chemistry at the UW-Madison School of Medicine and Public Health.

Using methods in mass spectrometry, RNA sequencing, and machine learning, the researchers explored a database of more than 17,000 different proteins, metabolites, lipids, and RNA transcripts associated with clinical outcomes.

They identified 219 molecules and genes that influence blood coagulation, vessel damage, inflammation, and other biological process reported to play a role in severe disease.

We had to think hard about how to actually compare it to the existing data, says Ron Stewart, Morgridge investigator and associate director of bioinformatics whose team was tasked with analyzing the transcriptome data. What weve largely found is we recapitulated prior work, which is good.

One particularly unique aspect to the study, which contributed to the robust dataset, was the teams use of plasma samples.

Most of the research done in proteomics, the blood samples use the serum fraction that doesnt have the clotting factors, says Jaitovich. This is very important because patients with COVID-19 have accelerated clotting activity.

A metabolite called citrate is used as a therapeutic anticoagulant to decrease the likelihood of developing clotting. Yet the study revealed that the presence of metabolic citrate decreased as patients presented with more severe illness.

The fact that citrate is reduced in these patients will potentially indicate that the reduction facilitates the hypercoagulation phenotype that we found in these patients, says Jaitovich.

Another molecule possibly contributing to hypercoagulation in severe COVID-19 is a protein called gelsolin, which is normally released as a response to inflammation due to cellular injury or infection. Gelsolin was also reduced in the plasma samples from people with severe disease.

In addition to biomarkers associated with hypercoagulation, the team also identified a cluster of proteins involved with blood vessel damage, with higher abundance in severe COVID-19 samples.

There are all these factors upstream of the process that are actually being changed, that you need to address as much as just the process of clotting in order to manage this phenotype, says Evgenia Shishkova, assistant staff scientist in the Coon Lab.

The analysis also revealed increased levels of proteins and upregulated genes involved in neutrophil degranulation, which has been associated inflammation, thrombosis, and the development of ARDS.

So it seems like theres this really strong interplay between the inflammatory response and probably these thrombotic events, which are also being seen in the COVID patients, saysKatie Overmyer, associate director of theLaboratory for Biomolecular Mass Spectrometry at UW-Madison.

Finally, the multi-omic analysis revealed a network of high-density lipoproteinsthe proteins APOA1 and APOA2, and a group of lipids known as plasmalogens which act as antioxidants were all lower in the severe COVID-19 cases.

These aspects were not on our radar, says Jaitovich. The ability to merge these dimensions in one single unifying narrative allowed us to make sense of stuff that was completely obscured to us.

And by identifying these various molecules, it opens up the potential for developing targeted therapeutics that may help alleviate disease.

We can offer hard data for people who are specialists in all these different areas to go and maybe learn about the prospects that what theyre thinking might have an impact on COVID, says Coon.

The researchers made the data publicly available through an interactive web tool, covid-omics.app, where the scientific community has been comparing and analyzing the data along with their own workflows.

Coon adds, I think weve tried to do our best to highlight vignettes that we think are important, but the bigger impact is probably going to come from the community being able to dig into this.

Reference: Large-scale Multi-omic Analysis of COVID-19 Severity by Katherine A Overmyer, Evgenia Shishkova, Ian Miller, Joseph Balnis, Matthew N. Bernstein, Trenton M. Peters-Clarke, Jesse G. Meyer, Qiuwen Quan, Laura K. Muehlbauer, Edna A. Trujillo, Yuchen He, Amit Chopra, Hau Chieng, Anupama Tiwari, Marc A. Judson, Brett Paulson, Dain R. Brademan, Yunyun Zhu, Lia R. Serrano, Vanessa Linke, Lisa A. Drake, Alejandro P. Adam, Bradford S. Schwartz, Harold A. Singer, Scott Swanson, Deane F. Mosher, Ron Stewart, Joshua J. Coon and Ariel Jaitovich, Accepted 5 October 2020, Cell Systems.DOI: 10.1016/j.cels.2020.10.003

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Researchers Unravel the Network of Molecules That Influence COVID-19 Severity - SciTechDaily

(UroToday.com) While cisplatin-based chemotherapy is a mainstay for neoadjuvant and adjuvant treatment of patients with muscle-invasive bladder cancer (MIBC), and none of the reported biomarkers for predicting response have been implemented in the clinic thus far.

Dr. Ann Taber presented data from researchers at the Aarhus University Hospital, Denmark, where they performed comprehensive genomic, transcriptomic, epigenomic, and proteomic analysis of 300 MIBC patients treated with cisplatin-based chemotherapy to identify molecular changes associated with treatment response. Based on mutational signatures, they identified two patient groups: those characterized by mutations in a tri-nucleotide signature 5 context (SBS5) that are related to ERCC2 mutations, and those related to APOBEC mutations.

Expression data identified the basal/squamous gene expression subtype to be associated with poor cisplatin-based treatment response. Immune cell infiltration and high PD-1 protein expression was also significantly associated with treatment response; they identified a unique subset that corresponds to an immune desert, which was associated with poor treatment response (Figure 1).

Figure 1: Association of immune cell infiltration and cisplatin-based treatment response.

The authors then assigned patients to high and low genomic instability groups based on SBS5 mutations, indels, allelic imbalance and BRCA2 mutation status. Patients with high genomic instability had a response rate of 71% versus 49% for patients with low genomic instability (p = 0.007). Through further integration, they identified a group of patients with a very high response rate (80%) characterized by high genomic instability and non-basal/squamous gene expression subtype and a group of patients with a very low response rate (25%) characterized by low genomic instability and basal/squamous gene expression subtype (p<0.001, Figure 2).

Figure 2: Patient subclassification based on genomic instability and basal/squamous gene expression subtype.

The results highlight several molecular correlates of chemotherapy response. These findings are now the basis of a new clinical trial for the treatment of metastatic bladder cancer following radical cystectomy.1

Presented by: Ann Taber, Ph.D., Department of Molecular Medicine (MOMA), Aarhus University Hospital, Denmark.

Written by:Anirban P. Mitra, MD, Ph.D., Urologic Oncology Fellow, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter: @APMitra, with Ashish M. Kamat, MD, MBBS, President of IBCN and IBCG, Endowed Professor, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter:@UroDocAsh,at the International Bladder Cancer Network (IBCN) Annual Meeting, #IBCN2020, October 17, 2020.

References:1. Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy (TOMBOLA). ClinicalTrials.gov identifier NCT04138628.

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IBCN 2020: IBCN 2020: Molecular Correlates of Cisplatin-Based Chemotherapy Response In Muscle-Invasive Blad... - UroToday

In summary

Proposition 14 asks voters to spend nearly $8 billion to continue the stem cell research program at a time when the coronavirus pandemic has decimated the state budget.

For the second time in 16 years, California voters will decide the fate of the states multi-billion dollar stem cell research program that established the state as a worldwide leader.

How the times have changed.

In November, as the pandemic drags on, Proposition 14 asks voters to spend nearly $8 billion to continue the program during a period when the research environment has significantly evolved and coronavirus has battered the states budget.

The bond measure would approve $5.5 billion in bonds to keep the states stem cell research agency running and grants flowing to California universities and companies.

At least $1.5 billion would be earmarked for brain and central nervous system diseases like Alzheimers and Parkinsons. The overall cost of the bonds and their interest totals about $7.8 billion, according to the state legislative analyst. The state would pay about $260 million annually for 30 years, or about 1 percent of Californias annual budget.

Proposition 14 is essentially a repeat with a bigger price tag and a few tweaks of Proposition 71, which California voters approved in 2004 after then-President George W. Bush prohibited, on religious grounds, all federal funding of any stem cell research using human embryos.

The bond measure would approve $5.5 billion in bonds to keep the states stem cell research agency running and grants flowing to California universities and companies.

That groundbreaking measure authorized $3 billion in state bonds to create the states stem cell research agency, the California Institute for Regenerative Medicine, and fund grants for research into treatments for Alzheimers disease, cancer, spinal cord injuries and other diseases.

The institute has nearly used up its original funding, so Prop. 71s author, real estate investor and attorney Robert N. Klein II, led a new effort to get Prop. 14 on the November ballot.

This time, embryonic stem cell research is in a much different place, with federal funding no longer blocked and more funding from the biotech industry.

Voters will want to consider what Californias previous investment in stem cell research has accomplished. Its a nuanced track record.

While many scientific experts agree that Prop 71 was a bold social innovation that successfully bolstered emerging stem cell research, some critics argue that the institutes grantmaking was plagued by conflicts of interest and did not live up to the promises of miracle cures that Prop. 71s supporters made years ago. Although the agency is funded with state money, its overseen by its own board and not by the California governor or lawmakers.

The agency had done a very good job of setting priorities for stem cell research, including research using human embryos, and doling out $300 million annually to build up California as a regenerative medicine powerhouse, according to a 2013 evaluation by the National Academies of Science, Engineering and Medicine.

But the report also found that because the institutes board is made up of scientists from universities and biotech firms likely to apply for grants, board members had almost unavoidable conflicts of interest.

Because human stem cells can develop into many types of cells, including blood, brain, nerve and muscle cells, scientists have long looked to them for potential treatments for currently incurable diseases and injuries. Researchers use two types of stem cells: embryonic stem cells, derived from unused human embryos created through in vitro fertilization, and adult stem cells, which are harder to work with but in some cases can be coaxed in a lab into behaving more like embryonic stem cells.

From the start, stem cell research has been ethically charged and politically controversial because human embryos are destroyed in some types of studies. Federal restrictions on the research have waxed and waned, depending on which political party holds power. While former President Bush restricted federal money for embryonic stem cell research, former President Obama removed those restrictions.

The Trump administration has restricted government research involving fetal tissue but not embryonic stem cells. However, anti-abortion lawmakers have called on the President to once again end federal funding for embryonic stem cell research.

California-funded research has led to one stem cell treatment for a form of Severe Combined Immunodeficiency known as the bubble baby disease. Children with the rare disease dont make enough of a key enzyme needed for a normal immune system. Without treatment, they can die from the disease if not kept in a protective environment. The U.S. Food and Drug Administration is now reviewing the treatment but has not yet approved it for widespread use.

Although many of the agencys early grants were for basic science, the institute also has supported 64 clinical trials of treatments for many types of cancer, sickle cell disease, spinal cord injuries, diabetes, kidney disease and amyotrophic lateral sclerosis, commonlyknown as Lou Gehrigs disease.

A June 2020 analysis by University of Southern California health policy researchers estimated that taxpayers initial $3 billion investment in the research institute helped create more than 50,000 jobs and generated $10 billion for the states economy.

Gov. Gavin Newsom has endorsed Proposition 14, and other supporters include the Regents of the University of California, the California Democratic Party, the Juvenile Diabetes Research Foundation, patient advocacy groups like the March of Dimes, and some local politicians and chambers of commerce.

Supporters have raised more than $8.5 million, including about $2 million from billionaire Dagmar Dolby, to pass the measure, according to California Secretary of State campaign finance reports.

The passage of Proposition 71 helped save my life, Sandra Dillon, a blood cancer patient, wrote in a San Diego Union-Tribune commentary supporting Proposition 14. She wrote that she had benefited from a drug developed with Institute-funded research that has been designated by the FDA as a breakthrough therapy.

It is unimaginable to think that Californians would vote to discontinue this amazing effort I dont know where I would be or what condition I would be in if it wasnt for the investment Californians made nearly two decades ago.

I think the agencys done good work, but this was never planned to be funded forever with debt.

Lawrence Goldstein, a UC San Diego professor of cellular and molecular medicine and stem cell researcher, said the grants were instrumental in furthering his research on treatments for Alzheimers disease and that Prop. 14 will help create new jobs. The agency has funded a great deal of very important stem cell medical research thats already produced terrific results and has the prospect of saving many more lives in the decade to come, he said.

Opponents include one member of the institutes board and a nonprofit that advocates for privacy in genetic research. They contend that the proposition seeks too much money and does not sufficiently address the conflicts of interest that cropped up after Prop. 71 was passed. They also note that private funding, including venture capital, for stem cell research has grown in recent years. Opponents had raised only $250 by late September, from a single contribution by the California Pro Life Council.

The editorial boards of some of Californias biggest newspapers also have opposed the measure, including the Los Angeles Times, the Orange County Register, the San Francisco Chronicle and the San Jose Mercury News/East Bay Times. The Fresno Bee, Modesto Bee, and San Luis Obispo Tribune newspaper editorial boards support Prop 14.

Jeff Sheehy, the only institute board member not to support Proposition 14, told CalMatters that the research environment has changed since voters initially approved state funding for stem cell research in 2004 and that California should prioritize other needs like education, health care, and housing.

I think the agencys done good work, but this was never planned to be funded forever with debt, Sheehy said. At this point the state cant afford it; were looking at a huge deficit.

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Prop. 14: In the COVID age, can California still afford its stem cell research program? - CALmatters

NEW YORK--(BUSINESS WIRE)-- The Canadian Cancer Trials Group (CCTG) today announced the commencement of a new sub-study evaluating CFI-400945, an oral, first-in-class inhibitor of Polo-like Kinase 4 (PLK4), in patients with metastatic castrate-resistant prostate cancer (mCRPC).

We are very excited to see the initiation of this trial, that builds on preclinical work demonstrating an association between loss of the tumor suppressor PTEN, a common alteration in this disease setting, and response to CFI-400945, says Dr. Mark Bray, Treadwell Chief Scientific Officer and Co-Founder.

This is the first trial that evaluates a precision medicine approach for patients with advanced prostate cancer using liquid biopsies for genomic testing. This innovative trial design, which incorporates liquid biopsy-based biomarker evaluation, helps meet the urgent need to identify more effective therapies for men with advanced prostate cancer, said Dr. Lesley Seymour, CCTGs Director, Investigational New Drug Program and a Medical Oncologist in the Department of Oncology at Queens University.

The study is supported by the Canadian Cancer Society, Prostate Cancer Canada and the Movember Foundation through a Translation Acceleration Grant to Tak Mak (The Princess Margaret Cancer Centre), the Canadian Clinical Trials Group and a team of co-investigators from across Canada.

Our understanding of the molecular drivers of prostate cancer is increasing, and for some of these molecular variations we have few therapeutic options, says the trail study chair Dr. Aaron R. Hansen, GU Medical Oncology Site Lead Division of Medical Oncology at Princess Margaret Cancer Center. The innovative trial design of IND234 will match men with metastatic castration resistant prostate cancer with agents designed to target their specific molecular abnormalities, in order to improve their outcomes.

This sub-study is part of the IND.234 - Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study. The primary endpoint is clinical benefit rate defined as proportion of patients who had PSA decline 50%, complete or partial objective response, or stable disease for 12 weeks.

The CCTG IND234 trial will be open at sites across Canada, for a full list of participating centers and for additional information about the study, please visit http://www.clinicaltrials.gov.

About CFI-400945

CFI-400945 is a first-in-class, oral selective and potent inhibitor of Polo-like Kinase 4 (PLK4), which regulates centriole duplication and thus mitotic progression. PLK4 is overexpressed in a variety of solid tumors and elevated expression is associated with poor clinical outcomes. Depletion of PLK4 expression in cancer cells by RNA interference leads to mitotic defects and cell death. PLK4 was identified as a drug target based on functional screening to identify vulnerabilities of genomically unstable breast cancers.

Anti-tumor activity of CFI-400945 has been shown in mice bearing human cancer xenografts, including robust tumor growth inhibition and durable tumor regression in primary tumor xenografts from breast cancer.

About Treadwell Therapeutics

Treadwell Therapeutics is a clinical-stage oncology company exploiting cancer cells vulnerabilities to develop first-in-class and best-in-class small molecules to address unmet needs in patients with cancer.

The Companys robust, internally developed pipeline includes a first-in-class PLK4 kinase inhibitor, CFI-400945 and a potentially best in class TTK inhibitor, CFI-402257 in Phase 2 studies, and CFI-402411, an oral immunomodulatory kinase inhibitor with activity toward HPK1, in Phase 1/2 studies. For more information, please visit http://www.treadwelltx.com.

About Canadian Cancer Trials Group (CCTG)

Celebrating its 40th year, the Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies in over 80 institutions across Canada and internationally. From its operations centre at Queens University, CCTG has led and participated in over 500 trials in over 40 countries aimed at improving survival and quality of life for all people with cancer. CCTG is a national program of the Canadian Cancer Society that provides core funding for the Group. To learn more about the CCTG, go to http://www.cctg.ca

View source version on businesswire.com: https://www.businesswire.com/news/home/20201019005662/en/

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Treadwell Announces Initiation of New Clinical Trial of CFI-400945 in Patients with Metastatic Castrate-Resistant Prostate Cancer (mCRPC) - BioSpace

Cancer immune plays a critical role in cancer progression. Tumour immunology and immunotherapy are one of the exciting areas in bladder cancer research. In this study, we aimed to develop an immune-related gene signature to improve the prognostic prediction of bladder cancer. Firstly, we identified 392 differentially expressed immune-related genes (IRGs) based on TCGA and ImmPort databases. Functional enrichment analysis revealed that these genes were enriched in inflammatory and immune-related pathways, including in 'regulation of signaling receptor activity', 'cytokine-cytokine receptor interaction' and 'GPCR ligand binding'. Then, we separated all samples in TCGA data set into the training cohort and the testing cohort in a ratio of 3:1 randomly. Data set GSE13507 was set as the validation cohort. We constructed a prognostic six-IRG signature with LASSO Cox regression in the training cohort, including AHNAK, OAS1, APOBEC3H, SCG2, CTSE and KIR2DS4. Six IRGs reflected the microenvironment of bladder cancer, especially immune cell infiltration. The prognostic value of six-IRG signature was further validated in the testing cohort and the validation cohort. The results of multivariable Cox regression and subgroup analysis revealed that six-IRG signature was a clinically independent prognostic factor for bladder cancer patients. Further, we constructed a nomogram based on six-IRG signature and other clinicopathological risk factors, and it performed well in predict patients' survival. Finally, we found six-IRG signature showed significant difference in different molecular subtypes of bladder cancer. In conclusions, our research provided a novel immune-related gene signature to estimate prognosis for patients' survival with bladder cancer.

Journal of cellular and molecular medicine. 2020 Oct 13 [Epub ahead of print]

Yongwen Luo, Liang Chen, Qiang Zhou, Yaoyi Xiong, Gang Wang, Xuefeng Liu, Yu Xiao, Lingao Ju, Xinghua Wang

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, DC, USA.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/33048468

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Identification of a prognostic gene signature based on an immunogenomic landscape analysis of bladder cancer. - UroToday

Meseret Derbew Molla,1 Yonas Akalu,2 Zeleke Geto,3 Baye Dagnew,2 Birhanu Ayelign,4 Tewodros Shibabaw1

1Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 3Department of Biomedical Sciences, School of Medicine, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia; 4Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia

Correspondence: Meseret Derbew MollaDepartment of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, PO Box 196, Gondar, Ethiopia, Tel +251918331617Email messidrm19@gmail.com

Abstract: Caspase-1 is the first and extensively studied inflammatory caspase that is activated through inflammasome assembly. Inflammasome is a cytosolic formation of multiprotein complex that aimed to start inflammatory response against infections or cellular damages. The process leads to an auto-activation of caspase-1 and consequent maturation of caspase-1 target molecules such as interleukin (IL)-1 and IL-18. Recently, the role of caspase-1 and inflammasome in inflammatory-induced noncommunicable diseases (NCDs) like obesity, diabetes mellitus (DM), cardiovascular diseases (CVDs), cancers and chronic respiratory diseases have widely studied. However, their reports are distinct and even they have reported contrasting role of caspase-1 in the development and progression of NCDs. A few studies have reported that caspase-1/inflammasome assembley has a protective role in the initiation and progression of these diseases through the activation of the noncanonical caspase-1 target substrates like gasdermin-D and regulation of immune cells. Conversely, others have revealed that caspase-1 has a direct/indirect effect in the development and progression of several NCDs. Therefore, in this review, we systematically summarized the role of caspase-1 in the development and progression of NCDs, especially in obesity, DM, CVDs and cancers.

Keywords: caspase-1, inflammasome, IL-1, IL-18, noncommunicable diseases

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chron | JIR - Dove Medical Press

Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the F.D.A.s vaccine advisory panel, said that pausing a trial is a huge logistical challenge especially for one like Johnson & Johnsons, with plans for 60,000 volunteers in 10 countries.

Its this big warship that you just stop moving, Dr. Offit said.

Once a trial is paused, a safety board may ask for a volunteer who experienced an adverse event to be unblinded in other words, to find out if the volunteer got the placebo or the treatment. If the volunteer received a placebo, then the treatment cant be the cause of the event and the trial can continue.

If it turns out that the volunteer got the treatment, the board does a flurry of detective work. The members look over the medical records. They may ask for more information about volunteers health or even order new tests not just for the people who experienced adverse events, but for everyone in the trial.

The board uses this evidence to come to a conclusion about whether the treatment most likely had anything to do with the event. On very rare occasions, for example, some vaccines can cause a nerve disorder called Guillain-Barr syndrome. But the condition takes weeks to develop. If a volunteer shows signs of Guillain-Barr syndrome on the day of a vaccine injection, it cant be the cause.

Regulators then review the decision of these boards and may accept it or ask for more information. For trials that are running in several countries at once, this review can make pausing a trial even more of a challenge. After AstraZeneca paused its global trials on Sept. 6 for a review, regulators in Brazil, India, Japan, South Africa and the United Kingdom all gave the green light for the trial to resume. But American regulators are still keeping the U.S. trial on pause as they continue to look over the evidence.

If a safety board rules that an adverse event most likely was not a result of the vaccine or treatment, it may allow the trial to start up again. If, on the other hand, theres some urgent problem a contaminated batch of drugs, for example the trial may have to stop. When the evidence isnt so clear, the board may let the trial resume with extra tests or exams. A second case of the same event might be more common than you would expect from chance, forcing the trial to end.

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3 Covid-19 Trials Have Been Paused for Safety. Thats a Good Thing. - The New York Times

Photo by Zo Meyers / inewsource

Above: The UC San Diego School of Medicine campus is shown on Feb. 1, 2020.

UC San Diego School of Medicine researchers announced Tuesday they have discovered a carbohydrate that the SARS-CoV-2 virus uses to latch onto a cellular molecule in the lungs, which has potential implications for treatment of COVID-19 patients.

Since January, researchers have known that the novel coronavirus primarily uses a molecule known as ACE2 which sits like a doorknob on the outer surfaces of the cells that line the lungs to enter and infect those cells. Finding a way to lock out that interaction between virus and doorknob as a means to treat the infection has become the goal of many research studies.

The UCSD researchers recently discovered the virus cannot grab onto that ACE2 doorknob without a carbohydrate heparan sulfate, which is also found on lung cell surfaces.

"ACE2 is only part of the story," said Jeffrey Esko, a professor of cellular and molecular medicine at UCSD and co-director of the Glycobiology Research and Training Center. "It isn't the whole picture."

Esko's study, published in the academic journal Cell, introduces a potential new approach for preventing and treating COVID-19.

His team demonstrated two approaches that can reduce the ability of the virus to infect human cells cultured in the lab by about 80 to 90%, either removing heparan sulfate with enzymes or using heparin as bait to lure and bind the coronavirus away from human cells.

Heparin, a form of heparan sulfate, is already a widely used medication to prevent and treat blood clots.

Esko's team has long studied heparan sulfate and the role it plays in health and disease.

The team discovered that the virus binds to heparin. When heparin is bound, the virus is able to bind to ACE2. The virus, the researchers found, must bind both heparan sulfate on the cell surface and ACE2 in order to get inside human lung cells grown in a laboratory dish.

With this viral entry mechanism established, the researchers next set about trying to disrupt it. They found that enzymes that remove heparan sulfate from cell surfaces prevent SARS-CoV-2 from gaining entry into cells. Likewise, treatment with heparin also blocked infection. The heparin treatment worked as an anti-viral at doses currently given to patients, even when the researchers removed the anticoagulant region of the protein the part responsible for preventing blood clots.

Esko cautioned that the findings are still far from translating into a COVID-19 treatment for people.

Researchers will need to test heparin and heparan sulfate inhibitors in animal models of SARS-CoV-2 infection. In a related study, UC San Diego scientists are also exploring the role human microbiomes, including the bacteria that live in and on the body, play in altering heparan sulfate and thus influencing a person's susceptibility to COVID-19.

"This is one of the most exciting periods of my career all of the things we've learned about heparan sulfate and the resources we've developed over the years have come together with a variety of experts across multiple institutions who were quick to collaborate and share ideas," Esko said.

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UCSD Researchers Discover Carbohydrate In Lungs That COVID-19 Uses To Infect - KPBS

A novel publication in the Nature journal Neuropsychopharmacology asserts that the stress of racism produces an increased risk for mental health disorders like anxiety and post-traumatic stress disorder in the Black community, especially in the current climate brought on by COVID-19 and the Black Lives Matter movement, leading to a critical need to utilize science to understand racisms true biological impact.

Wayne State University School of Medicine Professor of Psychiatry and Behavioral Neurosciences and the David and Patricia Barron Endowed Chair in PTSD and Trauma Neurobiology Tanja Jovanovic, Ph.D., wrote The critical importance in identifying the biological mechanisms underlying the effects of racism on mental health with Tracy Bale, Ph.D., a professor of Pharmacology at the University of Maryland School of Medicine in Baltimore.

Dr. Jovanovic has studied the impact of trauma on the brain and behavior in primarily African American urban communities for more than 15 years. The focus of her work has been in exposure to neighborhood and domestic violence, and post-traumatic stress disorder. She is now investigating the impact of racial discrimination above and beyond that of other types of trauma.

It is clear that the impact of racism is chronic, pervasive, and for many, unavoidable. Moreover it leaves the brain and body vulnerable to many disorders, including PTSD and many physical diseases, she said.

Her collaborator is a leading expert in understanding the impact of chronic stress on a molecular level. The duo decided to work together to examine the impact of the chronic stress of racism on biology. For a year, they studied biomarkers of stress that are also linked to immune system function.

Weve known for a long time that experiences of racial discrimination have a deep and long-term effect on psychology and mental health, and that there are substantial health disparities in that African American men and women are more likely to suffer from many medical illnesses compared to white individuals, Dr. Jovanovic said. A large part of this is due to systemic racism in health care, however, we believe racism also leaves an imprint on the body, which has not been well understood.

Dr. Bale works primarily with animal models of chronic stress and focuses on epigenetic and proteomic signatures of stress. Dr. Jovanovic focuses on African American women and children with urban trauma exposure who have experienced significant racism.

In writing this article, I contributed the information from individuals in Detroit reporting experiences of racism, especially in the current context of the Black Lives Matter movement, whileDr. Bale reported on the state-of-the art molecular methods that show the greatest promise as biomarkers of chronic stress and immune function, Dr. Jovanovic said.

She wants the field of stress and trauma research to focus on the impact of racism on the brain and the body. The duo are working on a series of grants and publications that describe these biological mechanisms in African American men and women in Detroit.

Black communities have been disproportionally affected by COVID-19; the pandemic has uncovered both systemic disparities and health-related vulnerability. It is truly of critical importance that we understand and mitigate the root causes of these vulnerabilities, she said.

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New article shows how science could reveal racism's real impact on the body and brain - The South End

Cardiologist to the whos who of Houston for decades, Dr. James T. Willerson died at CHI St. Lukes Hospital Wednesday as the result of a long illness. He was 80. Most recently serving as president emeritus of the Texas Heart Institute, Willerson was recognized internationally for seminal research in stem cells for the repair of hearts and cardiovascular vessels injured by heart attacks.

Among those who counted Willerson as both a friend and personal cardiologist were former Secretarty of State James A. Baker, former Houston Mayor Bob Lanier, philanthropists Margaret Williams and Jeanie Kilroy, art dealer Meredith Long, famed restaurateur Tony Vallone and even famed heart surgeon Dr. Denton Cooley.

In fact, Willerson credited his meeting with Cooley when he was 14 years old, at a time when Cooley and his team had performed 10,000 heart operations, with leading him into cardiology. It was the beginning of a lifelong friendship and collaboration at the Texas Heart Institute.

So committed to his patients, Willerson was known to return phone calls to them back in Houston whether he was in China, Turkey or South America. His quiet nature and often abrupt manner in the exam room would belie his intense passion for serving his patients. He was at the very least once seen weeping at the funeral of one of his patients.

On the Texas Heart Institute Website, THI board chairman Eric Wade notes, Dr. Willerson lived a tremendous life defined by curiosity and an eternally burning flame for the study of the human heart and its myriad complexities, and on behalf of the Texas Heart Institute Board of Trustees, it is with a heavy heart that I share the news of his passing.

His bio at Texas Heart Institute tallies his numerous lauded positions and accolades: President of The University of Texas Health Science Center in Houston from 2001-2008, recently retired as the Edward Randall III Professor of Internal Medicine at The UT Medical School at Houston. He holds the Dunn Chair in Cardiology Research at THI, the Willerson/OQuinn Chair at THI, the James T. Willerson, MD Distinguished Chair in Cardiovascular Diseases at UT Southwestern Medical School in Dallas and The Institute of Molecular Medicine IMM at the University of U.T. Health Houston. He has been named a Distinguished Alumnus at the University of Texas, Austin, and at the Baylor College of Medicine. A swimming scholarship is named in his honor at The University of Texas at Austin.

Born in Lampasas to two physicians, Willerson graduated Phi Beta Kappa from the University of Texas where he led the swimming team to a state championship. But it was UT football that was his passion second only to medicine. He attended Baylor College of Medicine in Houston and completed his training in internal medicine and cardiology at Massachusetts General Hospital in Boston and Harvard Medical School.

Funeral arrangements are being handled by Geo. H. Lewis & Sons.

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Highly Revered Cardiologist Dr. James T. Willerson Passes Away at St. Luke's in Houston - PaperCity Magazine

Individuals with severe psychiatric disorders have a reduced life expectancy compared to the general population. At the biological level, patients with these disorders present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). To date, the role of the interplay between inflammation and telomere dynamics in the pathophysiology of severe psychiatric disorders has been scarcely investigated. In this study we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort comprised of 40 patients with bipolar disorder (BD), 41 with schizophrenia (SZ), 37 with major depressive disorder (MDD), and 36 non-psychiatric controls (NPC). TL was shorter in SZ and in MDD compared to NPC, while it was longer in BD (model F=20.128, p=8.7310, effect of diagnosis, F=31.870; p=1.0810). There was no effect of the different classes of psychotropic medications, while duration of treatment with mood stabilizers was associated with longer TL (Partial correlation controlled for age and BMI: correlation coefficient = 0.451; p=0.001). Levels of high-sensitivity C-Reactive Protein (hsCRP) were higher in SZ compared to NPC (adjusted p=0.027), and inversely correlated with TL in the whole sample (r=-0.180; p=0.042). Compared to NPC, patients with treatment resistant (TR) SZ had shorter TL (p=0.001), while patients with TR MDD had higher levels of tumor necrosis factor- (TNF) compared to NPC (p=0.028) and to non-TR (p=0.039). Comorbidity with cardio-metabolic disorders did not influence the observed differences in TL, hsCRP, and TNF among the diagnostic groups. Our study suggests that patients with severe psychiatric disorders present reduced TL and increased inflammation.Fig. 1The figure shows diminished fluorescence intensity of telomeres of patients with schizophrenia (a) compared to major depressive disorder (b), bipolar disorder (c) and non-psychiatric controls (d). Telomere probe (red); DAPI-stained metaphases (blue). Note: no evidence of FISH signal randomly observed mainly in SZ chromosomes indicates that telomere shortening reached a size of the exameric sequence that is under the PNA-FISH resolution (200base pairs).Fig. 2a shows the difference in telomere length (TL) among the four diagnostic groups (effect of diagnosis F=31.87, p=1.0810). b shows the difference in levels of high sensitivity C-reactive protein (hsCRP) among the four diagnostic groups (effect of diagnosis F=4.680, p=0.004). Levels are expressed as mg/L. Figure c shows the difference in levels of tumor necrosis factor alpha (TNF) among the four diagnostic groups (effect of diagnosis F=1.217, p=0.306). Levels are expressed as pg/mL. Graphs were obtained using the raw values (unadjusted), while the statistical significance for TL, hsCRP and TNF are based on post-hoc analysis with Bonferroni correction of the univariate models controlling of age, sex, and BMI as covariates. *p<0.05; **p<0.005; ***p<0.0005; ns, not significant. Bars represent mean and standard errors on the mean. NPC non-psychiatric controls, BD bipolar disorder, SZ schizophrenia, MD major depressive disorder.Fig. 3a shows the difference in TL among non-psychiatric controls (NPC), patients with treatment-resistant schizophrenia (TR), and patients with non-treatment resistant schizophrenia (non-TR) (effect of diagnosis F=6.927; p=0.002). b shows the difference in levels of tumor necrosis factor alpha (TNF) among non-psychiatric controls (NPC), patients with treatment-resistant major depressive disorder (TR), and patients with non-treatment resistant major depressive disorder (non-TR) (effect of diagnosis F=3.998; p=0.023). Graphs were obtained using the raw values (unadjusted), while the statistical significance for TL, hsCRP and TNF are based on post-hoc analysis with Bonferroni correction of the univariate models controlling of age, sex, and BMI as covariates. *p<0.05; **p<0.005; ns, not significant. Bars represent mean and standard errors on the mean.Fig. 4Partial correlation between hsCRP and TL in the whole sample controlled for Body Mass Index (BMI) and age. Correlation coefficient=-0.180, p=0.042. TL telomere length, hsCRP high sensitivity C-reactive protein.

PubMed

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Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications. - Physician's Weekly

The ARK Genomic Revolution Multi-Sector Fund (CBOE: ARKG) turns six years old next month and over that time, its developed a reputation as one of the best-performing healthcare ETFs, biotechnology or otherwise.

That success is attributable to the ability of ARK Invests managers to identify disruptive genomics equities well before markets fully appreciate the growth stories behind those names.

Consider the investment opportunity found in the Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR, genome-editing platform. CRISPR is a genome-editing platform that will address the worlds most salient health issues. It is like a molecular swiss army knife with a rapidly expanding number of tools that perform different functions.

The major premise behind ARK Funds, and likely the reason for the success is the belief that the market at large does not know how to efficiently price and value the type of innovation these ETFs are investing in, according to Seeking Alpha. The returns of the individual funds are excellent, and they are excellent over extended periods of time.

The actively managed ARKG offers investors a thematic multi-capitalization exposure to innovative elements that cover advancements in gene therapy bio-informatics, bio-inspired computing, molecular medicine, and pharmaceutical innovations.

ARKG includes companies that merge healthcare with technology and capitalize on the revolution in genomic sequencing. These companies try to better understand how biological information is collected, processed, and applied by reducing guesswork and enhancing precision; restructuring health care, agriculture, pharmaceuticals, and enhancing our quality of life.

Theres potentially epic growth to be had with ARKG because of where many of the funds components are in the clinical trial stages.

One of the biggest drivers for this placement, in my mind, is centered in the stages of clinical trials that most of the vaccine and therapeutics in the holdings are in, according to Seeking Alpha. They are mostly, if not all, pre-phase 1 through phase 3, placing them at least a year or two away from being in the market. This means they are some time away from generating significant earnings and bringing valuation metrics more in line with the broader market.

Genomics companies try to better understand how biological information is collected, processed and applied by reducing guesswork and enhancing precision; restructuring health care, agriculture, pharmaceuticals, and enhancing our quality of life.

For more on disruptive technologies, visit our Disruptive Technology Channel.

The opinions and forecasts expressed herein are solely those of Tom Lydon, and may not actually come to pass. Information on this site should not be used or construed as an offer to sell, a solicitation of an offer to buy, or a recommendation for any product.

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Why This Genomics ETF Is a Long-Term Winner - ETF Trends

FREMONT, Calif., Sept. 17, 2020 /PRNewswire/ -- The global precision medicine marketis projected to reach $278.61 billion by 2030, reveals a premium market intelligence report by BIS Research. The study also highlights that the market is set to witness a CAGR of 11.13% during the period between 2020 and 2030.

The comprehensive study of the global precision medicine market by BIS Research extensively covers the following:

The detailed report is a compilation of 19 Market Data Tables and 330 Figures spread through 529 Pages and in-depth TOC on "Global Precision Medicine Market"

Besides these parameters, the report also encompasses the market growth drivers, opportunities, market restraining factors, competition mapping, segmental analysis, and a visual dashboard of 1400+ products.

The BIS Research report indicates that the increasing number of genetic tests taken, the growing demand for reliable next-generation sequencing (NGS) results, the rising prevalence of infectious diseases, and the improving funding scenario in the field of precision medicine, among others, are fueling the growth of the market.

It also highlights the various emerging opportunities, such as growth in emerging nations, capitalization on the high prevalence of cancer, and the evolution of technology in healthcare, that can be leveraged by players operating in the market.

Additionally, the market intelligence report by BIS Research throws a spotlight on the key industry trends that have a humungous influence in shaping the industry going forward. Some of these trends include the emergence of advanced stabilization products, regulated vs. multimodal analysis, collaborations and partnerships, and several other key trends.

View the Report from BIS Research: Global Precision Medicine Market

Data from different segments of the market has been analyzed minutely to gain a holistic view of the market. These segments include types of products offered, technologies used, sources used, applications, and regions. Each of these segments is further categorized into sub-segments and micro-segments to compile an in-depth study.

The technology and ecosystem analysis of the global market includes data analysis on the satisfaction level of different pricing analysis of preferred instruments, accessories and components, and consumables. The study is majorly centered on the sub-segments and micro-segments of the different product markets, such as consumables and instruments. The consumables are further categorized into kits and reagents.

Emphasizing the dominance of North America in global precision medicine market in 2019 and 2020, Nitish Kumar Singh, Lead Analyst BIS Research, states, "InNorth America, several established diagnostics manufacturers are focusing on expanding their portfolio in NGS-based molecular diagnostics and are collaborating with service providers and pharmaceutical giants to co-market molecular diagnostics solutions with its complementary precision medicine solutions. Moreover, the U.S. government is undertaking a number of initiatives to develop of precision drugs and tests for oncology and non-oncology diseases and provide funds to new startups in the molecular diagnostics and precision medicine field."

Request for a Sample: https://bisresearch.com/requestsample?id=964&type=download

Key insights are drawn from in-depth interviews with the key opinion leaders of more than 40 leading companies, market participants, and vendors. The key players profiled in the report includeAbbott Laboratories, Almac Group Ltd, Amgen Inc., ANGLE plc, Astellas Pharma Inc., Astra Zeneca PLC, ASURAGEN INC., Bio-Rad Laboratories, Inc., bioMrieux SA., Bristol-Myers Squibb Company, Cardiff Oncology, CETICS Healthcare Technologies GmbH, Danaher Corporation, Eli Lilly and Company Limited, Epic Sciences, Inc., F. Hoffmann-La Roche Ltd, GE Corporation, Gilead Sciences, Inc., GlaxoSmithKline Plc, Illumina, Inc., Intomics A/S, Johnson & Johnson Company, Konica Minolta, Inc., Laboratory Corporation of America, MDx Health, Inc., Menarini Silicon Biosystems, Inc., Merck & Co., Inc., Myriad Genetics, Inc., Novartis AG, Oracle Corporation, Partek, Inc., Pfizer, Inc., QIAGEN N.V., Quest Diagnostics Inc, Randox Laboratories Ltd., Sanofi SA, Sysmex Corporation, Teva Pharmaceuticals Industries Ltd., and Thermo Fisher Scientific, Inc.

The report also offers strategic recommendations that can help organizations in tracking various products, trends, and technologies that are changing the dynamics of the market. The recommendations by BIS Research also offer bespoke research services to help organizations meet their objectives.

Who should buy this report?

How can this market intelligence report on precision medicine add value to an organization's decision-making process?

Insightful Questions Covered to Enable Companies take Strategic Decisions

Related BIS Research Market Reports:

Global NGS Sample Preparation Market - Analysis and Forecast, 2019-2025

Global Next Generation Sequencing (NGS) Market - Analysis and Forecast, 2019-2024

Global Rare Disease Diagnostics Market - Analysis and Forecast, 2018-2025

About BIS Research:

BIS Researchis a global B2B market intelligence and advisory firm focusing on deep technology and related emerging trends which can disrupt the market dynamics in the near future. We publish more than 200 market intelligence studies annually that focus on several deep technology verticals.

Our strategic market analysis emphasizes on market estimations, technology analysis, emerging high-growth applications, deeply segmented granular country-level market data, and other important market parameters useful in the strategic decision-making for senior management.

BIS Research offers syndicate as well as, custom studies, and expert consultations to firms, providing them specific and actionable insights on novel technology markets, business models, and competitive landscape.

BIS Healthcare vertical offers intelligence in the healthcare technology market for Medical Devices, Digital Health, Life Sciences, Robotics and Imaging, Information Technology, Precision Medicine, and other emerging healthcare technologies, covering the entire industry spectrum. In the past 5 years, BIS Healthcare has published more than 50 reports under the precision medicine banner. Additionally, BIS Research has been nominating Top 25 Voices in Precision Medicine on its Insight Monk platform for the past two years successfully.

Contact:

Bhavya BangaEmail: [emailprotected] BIS Research Inc.39111 PASEO PADRE PKWY STE 313,FREMONT CA 94538-1686Visit our Blog @ https://blog.bisresearch.com/ Connect with us on LinkedIn @ https://www.linkedin.com/company/bis-researchConnect with us on [emailprotected] https://twitter.com/BISResearch

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BIS Research Report Highlights the Global Precision Medicine Market to Reach $278.61 Billion by 2030 - PRNewswire

The research led by Jeremy Wood, Zach Porterfield and Jamie Sturgill in the Department of Internal Medicine; Beth Garvy in Microbiology, Immunology & Molecular Genetics; and Wally Whiteheart in Molecular & Cellular Biochemistry, suggests localized inflammation in the lungs caused by COVID-19 may be responsible for the increased presence of blood clots in patients.

The study also provides evidence suggesting the risk of thrombosis could persist after the infection clears.

The study examined the blood of 30 COVID-19 patients including 15 who were inpatients in the intensive care unit, and 15 who received care as outpatients at UKs Infectious Diseases Clinic, along with eight disease-free volunteers who acted as a control group.

Compared to baseline, the COVID-19 patients had elevated levels of tissue factor, a protein found in blood that initiates the clotting process. Patients also had reduced levels of protein S, an anticoagulant that helps prevent blood clotting.

The researchers concluded that lung inflammation caused by COVID-19 is what leads to a decrease in protein S. Thisinflammation also causes immune and possible endothelial cell activation, which leads to increased tissue factor protein.

What weve learned is that the clotting is not caused by anything systemic. Localized inflammation in the lungs is whats driving this whole process, Wood said. With an increase in tissue factor and a deficiency in protein S, COVID-19 patients get more blood clotting without the ability to shut it down or control it.

The study additionally showed that protein S levels remained low in some patients even after they tested negative for COVID-19, which suggests that blood clotting issues may persist after infection and long-term monitoring of thrombotic risk may be necessary.

Wood says this preliminary data could be a cause for concern. Certain viruses like HIV are linked to a long-term deficiency in protein S, which causes an ongoing risk of thrombosis in patients. It is not yet known if COVID-19 could cause a similar persisting protein S deficiency.

Tissue factor and protein S are good markers to monitor for long-term thrombosis risk and the data suggest that we need to be monitoring these patients because were not seeing these parameters corrected immediately, Wood said.

The research team recently received a grant from UKsCenter for Clinical and Translational Science(CCTS) to begin a longitudinal study to look at these levels in patients over the next year.

This will help answer the question: will this risk remain like it is in the HIV patients or will it go away?

The study was funded in part by anAlliance Grantthrough the College of Medicine as well as UKsCOVID-19 Unified Research Experts (CURE) Alliancethroughthe Vice President for Research and the College of Medicine and the CCTS. It was a product of collaboration between a number of different groups at UK that have been studying COVID-19.

Additional collaborators includeMartha Sim, Meenakshi Banerjee and Hammodah Alfar in the Department of Molecular and Cellular Biochemistry; Melissa Hollifield and Jerry Woodward with Microbiology, Immunology and Molecular Genetics; Xian Li with the Saha Cardiovascular Research Center; Alice Thornton with the Division of Infectious Disease; and Gail Sievert, Marietta Barton-Baxter and Kenneth Campbell with CCTS.

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UK research getting to bottom of COVID clots - ABC 36 News - WTVQ

Patented CRISPRclean Technology is a Foundational Tool that Improves the Performance of Next-Generation Sequencing and Other Molecular Workflows by Increasing Sensitivity, Reducing Costs and Enabling Novel Discovery

CARLSBAD, CA, UNITED STATES - Sep 17, 2020 - Jumpcode Genomics - a genome technology company founded by industry veterans in 2016 focused on improving the understanding of human disease - today exited stealth mode and announced the commercial launch of its CRISPRclean technology. Initially available via three kits, CRISPRclean unlocks the power of next generation sequencing (NGS) by improving sensitivity, reducing costs and simplifying workflows. The company also announced that it has strengthened its leadership team with the addition of Yaron Hakak, Ph.D., as CEO. In addition, the company has added new advisors, including Dr. Stanley Nelson, vice chairman of Human Genetics at UCLA as consulting chief scientist, and Gary Schroth, Ph.D., vice president and distinguished scientist at Illumina, as a member of the companys scientific advisory board.

CRISPRclean technology is based on the in-vitro utilization of the CRISPR/Cas system to cleave and physically remove nucleic acid sequences pre- or post-NGS library preparation. This enables researchers to remove overabundant and uninformative sequences to allow discovery and detection of molecules previously undetectable (the needles). Like polymerase chain reaction (PCR), the technology broadly applies to many molecular biology techniques, particularly sequencing technologies.

Initial research applications focus on ribosomal RNA depletion, single cell analysis and repeat removal for whole genome sequencing. Additionally, Jumpcode Genomics is pursuing clinical applications, including the removal of human host molecules for a universal pathogen test and depletion of wild type alleles for somatic mutation detection in oncology. The technology seamlessly integrates into existing workflows and is agnostic to library preparation methods and sequencing platforms.

We aim to revolutionize the practice of molecular biology with our technology and to drive better results for researchers today and ultimately patients tomorrow, said Dr. Hakak, CEO of Jumpcode Genomics. When researchers perform NGS on biological samples, most molecules sequenced are uninformative, which results in a needle in a haystack problem. CRISPRclean solves this problem by simply removing the haystack.

The expansion of the leadership team and scientific advisory board enables Jumpcode Genomics to commercialize its technology and strengthen direct access to thought leaders in the scientific community.

About Jumpcode Genomics: Founded in 2016, Jumpcode Genomics aims to improve the understanding of human biology and the contribution to disease. The companys proprietary CRISPRclean technology utilizes the CRISPR/Cas system to deplete unwanted nucleic acid molecules from sequencing libraries. The process fits seamlessly within standard next generation sequencing workflows and works with most commercially available library preparation solutions. For more information, please visit: http://www.jumpcodegenomics.com

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Jumpcode Genomics Exits Stealth Mode, Unveils Technology that Addresses the 'Needle in the Haystack' Problem of Molecular Biology - Bio-IT World

HTG Molecular Diagnostics Inc. [NASDAQ: HTGM] surged by $0.0 during the normal trading session on Thursday and reaching a high of $0.35 during the day while it closed the day at $0.34. The company report on September 8, 2020 that HTG Molecular Diagnostics to Present Corporate Overview at Fall Investor Conferences.

HTG Molecular Diagnostics, Inc. (Nasdaq: HTGM), a diagnostic company whose mission is to advance precision medicine, today announced John Lubniewski, President and CEO of HTG, will present virtually at the H.C. Wainwright 22nd Annual Global Investment Conference and at the Cantor Fitzgerald Global Healthcare Conference. Details are as follows:.

About HTG.

HTG Molecular Diagnostics Inc. stock has also gained 6.01% of its value over the past 7 days. However, HTGM stock has declined by -52.85% in the 3 months of the year. Over the past six months meanwhile, it has lost -1.16% and lost -51.28% year-on date.

The market cap for HTGM stock reached $25.48 million, with 65.76 million shares outstanding and 49.64 million shares in the current float. Compared to the average trading volume of 4.77M shares, HTGM reached a trading volume of 2065978 in the most recent trading day, which is why market watchdogs consider the stock to be active.

Cantor Fitzgerald have made an estimate for HTG Molecular Diagnostics Inc. shares, keeping their opinion on the stock as Overweight, with their previous recommendation back on May 11, 2020. The new note on the price target was released on March 26, 2020, representing the official price target for HTG Molecular Diagnostics Inc. stock. Previously, the target price had yet another raise from $4.50 to $6, while Rodman & Renshaw kept a Buy rating on HTGM stock.

The Average True Range (ATR) for HTG Molecular Diagnostics Inc. is set at 0.04, with the Price to Sales ratio for HTGM stock in the period of the last 12 months amounting to 1.77. The Price to Book ratio for the last quarter was 1.22, with the Price to Cash per share for the same quarter was set at 0.44.

HTG Molecular Diagnostics Inc. [HTGM] gain into the green zone at the end of the last week, gaining into a positive trend and gaining by 6.01. With this latest performance, HTGM shares dropped by -27.00% in over the last four-week period, additionally sinking by -1.16% over the last 6 months not to mention a drop of -56.99% in the past year of trading.

Overbought and oversold stocks can be easily traced with the Relative Strength Index (RSI), where an RSI result of over 70 would be overbought, and any rate below 30 would indicate oversold conditions. An RSI rate of 50 would represent a neutral market momentum. The current RSI for HTGM stock in for the last two-week period is set at 37.10, with the RSI for the last a single of trading hit 41.28, and the three-weeks RSI is set at 37.50 for HTG Molecular Diagnostics Inc. [HTGM]. The present Moving Average for the last 50 days of trading for this stock 0.5115, while it was recorded at 0.3292 for the last single week of trading, and 0.5346 for the last 200 days.

Operating Margin for any stock indicates how profitable investing would be, and HTG Molecular Diagnostics Inc. [HTGM] shares currently have an operating margin of -102.09 and a Gross Margin at +53.60. HTG Molecular Diagnostics Inc.s Net Margin is presently recorded at -100.49.

Return on Total Capital for HTGM is now -49.79, given the latest momentum, and Return on Invested Capital for the company is -53.22. Return on Equity for this stock declined to -85.65, with Return on Assets sitting at -43.42. When it comes to the capital structure of this company, HTG Molecular Diagnostics Inc. [HTGM] has a Total Debt to Total Equity ratio set at 71.00. Additionally, HTGM Total Debt to Total Capital is recorded at 41.52, with Total Debt to Total Assets ending up at 37.72. Long-Term Debt to Equity for the company is recorded at 50.39, with the Long-Term Debt to Total Capital now at 29.47.

Reflecting on the efficiency of the workforce at the company, HTG Molecular Diagnostics Inc. [HTGM] managed to generate an average of -$172,301 per employee. Receivables Turnover for the company is 4.70 with a Total Asset Turnover recorded at a value of 0.43.HTG Molecular Diagnostics Inc.s liquidity data is similarly interesting compelling, with a Quick Ratio of 7.10 and a Current Ratio set at 7.40.

With the latest financial reports released by the company, HTG Molecular Diagnostics Inc. posted -0.15/share EPS, while the average EPS was predicted by analysts to be reported at -0.16/share. When compared, the two values demonstrate that the company surpassed the estimates by a Surprise Factor of 6.30%. The progress of the company may be observed through the prism of EPS growth rate, while Wall Street analysts are focusing on predicting the 5-year EPS growth rate for HTGM.

There are presently around $6 million, or 34.30% of HTGM stock, in the hands of institutional investors. The top three institutional holders of HTGM stocks are: NANTAHALA CAPITAL MANAGEMENT, LLC with ownership of 5,060,160, which is approximately 0% of the companys market cap and around 0.80% of the total institutional ownership; COWEN PRIME SERVICES LLC, holding 4,579,500 shares of the stock with an approximate value of $1.57 million in HTGM stocks shares; and PERKINS CAPITAL MANAGEMENT INC, currently with $0.83 million in HTGM stock with ownership of nearly -3.68% of the companys market capitalization.

Positions in HTG Molecular Diagnostics Inc. stocks held by institutional investors increased at the end of August and at the time of the August reporting period, where 17 institutional holders increased their position in HTG Molecular Diagnostics Inc. [NASDAQ:HTGM] by around 1,592,904 shares. Additionally, 17 investors decreased positions by around 3,162,056 shares, while 8 investors held positions by with 11,662,409 shares. The mentioned changes placed institutional holdings at 16,417,369 shares, according to the latest SEC report filing. HTGM stock had 7 new institutional investments in for a total of 1,062,389 shares, while 11 institutional investors sold positions of 2,750,997 shares during the same period.

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HTG Molecular Diagnostics Inc. [HTGM] Is Currently 1.85 above its 200 Period Moving Avg: What Dose This Mean? - The DBT News

Without masks and a vaccine, we could reach Herd Immunity from COVID-19, but deaths would skyrocket. We break down the science of it. USA TODAY

Scientists and physicians reacted with words such as aghast, despicable and outrageous over the weekend as news spread that White House appointeesinterfered with a basic national public health reportwhen it conflicted with PresidentDonald Trump'scoronavirus messaging.

Michael Caputo, the Health and Human Services assistant secretary for public affairs, acknowledged Saturday that since June, he and an adviser havescrutinized and at times pushed for changes toa weekly health report distributed by the U.S. Centers for Disease Control and Prevention.

The meddling, first reported by Politico,included efforts to stop the publication of a report last week on the use of hydroxychloroquine,a malaria drug often touted by Trump, delaya10-state study of COVID-19 infection statistics in Juneand another on the spread of coronavirus at a Georgia sleep-away camp.

The Morbidity and Mortality Weekly Report is a series of dry and sometimes dense briefupdates on public health incidents that comeout on Thursdays. They typically describeevents or topicsand are an important way for doctors and health officials to get the latest data.

Monday, members of the House Select Subcommittee on the Coronavirus Crisis sent a letter to HHS Secretary AlexAzar and CDC Director Robert Redfield requesting documents pertaining to the efforts to block the publicationof "accurate scientific reports."

"We are gravely concerned by reports showing that the Presidents political appointees at HHS have sought to help him downplay the risks of the coronavirus crisis by attempting to alter, delay, and block critical scientific reports from CDC," the letter said.

Approving a vaccine in the U.S. usually takes years, but COVID-19 vaccines are moving through in record time. What does that mean? USA TODAY

The sprint to create a COVID-19 vaccine started in January. The finish line awaits.

Dr. William Schaffner, who is on the publications editorial board, said he was aghast and appalled" by the reported attempts to delay, stop or change reports.He described the publication as a vital part of the global conversation among public health officials who track diseases and dangers.

It has been the voice of the U.S. governments health system, of integrity and scientific rigor, for years," said Schaffner, a professor and infectious disease expert at the Vanderbilt University School of Medicine in Nashville, Tennessee."Indeed, the MMWR has been a model for other countries ministries of public health for creating similar newsletters in their countries.

The interference is not just anti-science butdisinformation intended to deceive the American public, said Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in La Jolla, California.

This is outright egregious. Its despicable, Topol said, accusing Redfieldand otherleadersof allowing the agency to be hijacked by politics.

Coronavirus in America: Here's how the virus is spreading, state by state

What were seeing is multiple actors, important people who are just laying down, who are complicit with the anti-science machinations of the Trump administration, he said.

In an interview Saturday with The Washington Post,Caputo alleged the content of the MMRWis being politicized by the agency itself.

But in an election year, and in the time of COVID-19,its no longer unanimously scientific. Theres political content, The Post quoted Caputo as saying.

On a Facebook livestream on Sunday night, Caputo railed against what he termed"sedition" among CDC scientists, the New York Times reported Monday.They havent gotten out of their sweatpants except for meetings at coffee shops to plot how theyre going to attack Donald Trump next, the Times reported him as saying. The Facebook video has since been removed.

On Twitter,Dr. Sherri Bucher, a global health researcher, wrote,There are no words to articulate how horrific this is. Trust & credibility, shattered, overnight. MMWR has been, for a long time, one of the most reliable, steadfast, scientific resources; unquestioned veracity, impeccable reputation for quality of data/analysis. No longer.

It is not unusual for communicationpeople within the CDC to be involved in an MMWR report before publication, said Dr. Patrick Remington, a member of the journals editorial board and a former CDC staffer.

That involvement was previously restricted to officials within the agency who let political leaders know what was coming so they could be prepared with a communicationstrategy, said Remington, associate dean for public health at the School of Medicine and Public Health at theUniversity of Wisconsin-Madison.

What is unusual is the allegation that the political process is attempting to influence the scientific conclusions. And thats a concern, Remington said.

A member of the editorial board for 14 years, Remington said the body meets roughly once a year to help decide the publication's big-picture vision. Its most recent meeting was in February.

Coronavirus Watch: An American dies of COVID-19 every 2 minutes

The board is not involved in the publication's day-to-day operations, and members knew nothing about the accusations of interferenceuntil they read about them, he and others said.

Jeff Niederdeppe, another member of the MMWR editorial board and a professor of public health communicationat Cornell University, said political meddling could erode public faith and cause long-term damage to the publication.

The big issue here in my mind is the fundamental undermining of trust, he said, both in the CDC generallyand among the public health practitioners who rely on the MMWR to make policy decisions. If that very foundation is being politicized, its incredibly alarming.

Regaining trust is a challenge, he said, and should begin with an immediate response from the CDC, which has not commented on the allegations.

If the concerns are confirmed, Niederdeppe said, Id be interested in convening with the other members of the MMWR editorial board to figure out what we could do in this role.

The Notes from the Field section of the MMWR previews small investigations by state or local health departments that illustrate a specific problem.

Theyre like an alert mechanism, Schaffner said.

MMWRs have described American heat-related deaths by sex and age, top foods contributing to high-salt intake, an outbreak of tuberculosis among workers at food processing plants and drinking rates among pregnant women.

Dr. Jennifer Kates, senior vice president of the nonprofit Henry J. Kaiser Family Foundation, which focuseson health issues, described the MMWR as the go-to public health publication.

The MMWR predates the CDC, beginning as a publication of the U.S. Public Health Servicein 1878.

Kates said she was disturbed by what appears to be the insertion of politics into a well-respected scientific journal. In general, the politicization of COVID has been the enemy of public health, she said.

MMWR reports are written by CDC staff, as well as public health workers and physicians nationwide. The one- to two-page reports are known for their meticulous and careful editing, a process those who'vegone through it described as harrowing.

If youve ever been involved as a co-author of one of those reports, its painful how carefully every sentence is reviewed for scientific rigor, for precision,Schaffner said.

The Centers for Disease Control and Prevention issues the Morbidity and Mortality Weekly Report every Thursday.(Photo: Jessica McGowan, Getty Images)

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Scientists outraged by White House appointees' meddling with coronavirus information: 'Outright egregious' - USA TODAY

DetailsCategory: Proteins and PeptidesPublished on Friday, 18 September 2020 10:55Hits: 190

- Series A led by Canaan Partners, Samsara BioCapital and The Column Group- Foundational research into cytokine structural biology and immune function licensed from Stanford University- Nils Lonberg joins founding investors on board of directors

MENLO PARK, CA, USA I September 17, 2020 I Synthekine Inc., an engineered cytokine therapeutics company, today announced the closing of an $82 million Series A financing. The financing was co-led by Canaan Partners, Samsara BioCapital and The Column Group, with participation from other undisclosed investors. Synthekine was founded by K. Christopher Garcia, Ph.D., to leverage discoveries showing that cytokines can be tuned to enhance their therapeutic effects.

Synthekine combines strengths in immunology, structural insights on cytokines and multiple engineering technologies to create optimized therapeutics against new and validated cytokine targets for the treatment of cancer and autoimmune disorders. Proceeds from this Series A financing will be used to advance Synthekines lead therapeutic programs into clinical studies, expand its discovery pipeline and hone its proprietary cytokine engineering platforms. The company currently has two lead programs in IND-enabling development: STK-012, an engineered Interleukin-2 (IL-2) partial agonist for the treatment of cancer, and the combination of STK-009 and SYNCAR-001, an orthogonal IL-2 ligand and a CD-19 CAR-T-cell therapy being studied in combination.

Cytokines have a fundamental role in the immune system and represent an enormous opportunity for innovative therapeutics. However, most cytokines broadly activate a wide range of cells that can simultaneously stimulate and suppress the immune system, making drug development against these targets challenging, said Debanjan Ray, chief executive officer of Synthekine. Chris Garcia has shown, for a wide range of therapeutically important cytokines, that cytokine efficacy and toxicity can be decoupled through structure-based protein engineering. These findings mean that many cytokines previously thought to be unsuitable as therapeutics can be transformed into safe and effective drugs. In addition to our highly differentiated IL-2-based programs, we have assembled multiple best-in-class technologies and an accomplished team to develop cytokine therapeutics by engineering them at the molecular level to enhance their activity and selectivity.

Unlocking cytokine therapeutics through unique structural biology insights

Cytokines are small, soluble proteins that are powerful regulators of the immune system and can stimulate a wide range of immune cells, primarily driven by their binding and interaction with cell surface receptors. Most cytokines are pleiotropic, meaning that a given cytokine can exert a range of responses across multiple cell types. Pleiotropy has proven to be a significant obstacle in the development of cytokine therapeutics. Existing cytokine therapeutics, such as aldesleukin (Proleukin) and interferons, demonstrate meaningful efficacy in cancer and other diseases but are limited by significant side effects.

Synthekine has licensed several cytokine programs and platforms from Stanford University. Research conducted in the Garcia lab at Stanford led to insights into the interaction of cytokines and their receptors, allowing researchers to engineer modified cytokines to deliver selective activity to particular cell types of therapeutic interest, giving them the potential for optimized efficacy, a larger therapeutic window and improved safety for patients. This research has been responsible for determining the three-dimensional structures for many different cytokine/receptor complexes, including IL-1, IL-2, IL-4, IL-6, IL-13, IL-15, IL-17, IL-23 and the three different classes of interferons.

A deep preclinical pipeline and proprietary platform

Synthekine is advancing several preclinical programs and innovative platform technologies. These include:

A collaborative company formation effort and seasoned leadership team

The founding members of Synthekines board of directors include Tim Kutzkey, Ph.D., managing partner of The Column Group; Srinivas Akkaraju, Ph.D., founding partner of Samsara BioCapital; and Julie Grant, general partner at Canaan Partners. Synthekine has also appointed biopharma veteran Nils Lonberg as an independent member of its board of directors.

Synthekines executive team is led by Debanjan Ray as chief executive officer. Mr. Ray was previously chief financial officer and head of business development at CytomX Therapeutics, where he was responsible for leading financing efforts and securing multiple strategic collaborations with major pharmaceutical companies that generated more than $400 million in upfront payments and up to $4 billion in milestones. The executive team also includes Martin Oft, M.D., as chief development officer, Rob Kastelein, Ph.D., as head of therapeutic discovery and Gregory Yedinak as senior vice president of technical operations.

Synthekines scientific advisory board is led by its founder, K. Christopher Garcia, Ph.D., professor of molecular and cellular physiology and structural biology at Stanford University School of Medicine, a Howard Hughes Medical Institute (HHMI) investigator and a member of both the National Academy of Sciences and the National Academy of Medicine.

About Synthekine

Synthekine is an engineered cytokine therapeutics company developing disease-optimized treatments. The company uses immunological insights to guide targeted protein engineering to generate transformative medicines for cancer and autoimmune disorders. Using the principles of cytokine partial agonism and immunological specificity, Synthekine designs differentiated therapeutics to be both safe and efficacious. Its lead programs have shown promising efficacy and tolerability in preclinical studies, and it is developing additional cytokine partial agonists that selectively modulate key pathways of the immune system. For more information, visit http://www.synthekine.com.

SOURCE: Synthekine

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Synthekine Launches with $82 Million Series A Financing to Advance Pipeline of Engineered Cytokine Therapeutics Optimized for Cancer and Autoimmune...

Fierce Healthcare honors the precision medicine platform for clinical information management capabilities

RALEIGH, NC, UNITED STATES - Sep 16, 2020 - Fierce Healthcare released its annual Fierce Innovation Report this week, naming 2bPrecise the industrys top clinical information management solution. The intent of the awards program, according to Fierce Healthcare, is to showcase organizations that over the past 12 months have demonstrated innovative solutions that have the greatest potential to save money, engage patients, or revolutionize the industry.

Cloud-based, the 2bPrecise platform consumes molecular data from labs and clinical information from the EHR, synthesizing them into a clinical-genomic ontology. The resulting precision medicine insights are delivered to providers within their familiar workflow across any EHR. Plus, the solution is built to interact with evolving knowledge sources and care guidelines.

These unique capabilities enable health systems to leverage precision medicine insights in myriad ways - driving efficient workflows for genomics interventions, extracting population analytics, building cohorts for trial recruitment, enabling participation in research studies and more.

2bPrecise was similarly honored with the MedTech Breakthrough award as Best Overall Genomics Solution earlier this year, and the company received Microsoft Corp.s 2020 Health Innovation Award in the category of Reimagine Healthcare. Industry Wired magazine further recognized 2bPrecise as one of the Top 8 Precision Medicine Companies in the USA this year.

We are honored to receive this latest recognition from Fierce Healthcare, said 2bPrecise CEO Assaf Halevy. The entire 2bPrecise team is driven to create excellent solutions to support clinical decision making within the providers workflow - while simultaneously helping improve outcomes and the patient experience.

Additional winners announced by Fierce Healthcare include Roche (data analytics/business intelligence), Walgreens (digital/mobile health solutions), XSOLIS (financial/operational) and Centivo (population health management/patient engagement).

About 2bPrecise

The cloud-based 2bPrecise platform consumes genetic/genomic data from molecular labs and clinical information from EHRs, synthesizing them into a clinical-genomic ontology. The 2bPrecise Genomic EHR Mentor (GEM) brings the resulting precision medicine insights into a physicians EHR workflow for immediate and timely use. With discrete test results consolidated into an invaluable data set, provider organizations are likewise equipped to drive efficient workflows for genomic interventions, extract population analytics, design clinical intervention programs, build cohorts for trial recruitment, enable participation in research studies and more. Learn more at http://www.2bPreciseHealth.com.

Media Contact

Erica Navar

Account Executive

Aria Marketing (for 2bPrecise)

(909) 538-9541

enavar@ariamarketing.com

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2bPrecise Wins Industry Innovation Award - Bio-IT World

The pathophysiology of pain in neuropathy is complex and may be linked to sensory phenotypes. Quantitative sensory testing, a standardized method to evaluate sensory profiles in response to defined stimuli, assesses functional integrity of small and large nerve fiber afferents and central somatosensory pathways. It has revealed detailed insights into mechanisms of neuropathy, yet, it remains unclear if pain directly affects sensory profiles. The main objective of this study was to investigate sensory profiles in patients with various neuropathic conditions, including polyneuropathy, mononeuropathy, and lesions to the central nervous system, in relation to self-reported presence or absence of pain and pain sensitivity using the Pain Sensitivity Questionnaire.A total of 443 patients (332 painful and 111 painless) and 112 healthy participants were investigated. Overall, loss of sensation was equally prevalent in patients with and without spontaneous pain. Pain thresholds were equally lowered in both patient groups, demonstrating that hyperalgesia and allodynia is just as present in patients not reporting any pain. Remarkably, this was similar for dynamic mechanical allodynia. Hypoalgesia was more pronounced in painful polyneuropathy whereas hyperalgesia was more frequent in painful mononeuropathy (compared to painless conditions). Self-reported pain sensitivity was significantly higher in painful than in painless neuropathic conditions.Our results reveal the presence of hyperalgesia and allodynia in patients with central and peripheral lesions of the somatosensory system not reporting spontaneous pain. This shows that symptoms and signs of hypersensitivity may not necessarily coincide, and that painful and painless neuropathic conditions may mechanistically blend into one another.

PubMed

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No pain, still gain (of function): the relation between sensory profiles and the presence or absence of self-reported pain in a large multicenter...