tbuckley/cabot-search huggingface dataset:
The use of tissue‐engineered skin to demonstrate the negative effect of CXCL5 on epidermal ultraviolet radiation‐induced cyclobutane pyrimidine dimer repair efficiency
Authors: M.M. Dorr, R. Guignard, F.A. Auger, P.J. Rochette
Journal: British Journal of Dermatology (2020)

Ultraviolet radiation (UVR) is responsible for keratinocyte cancers through the induction of mutagenic cyclobutane pyrimidine dimers (CPDs). Many factors influence CPD repair in epidermal keratinocytes, and a better understanding of those factors might lead to prevention strategies against skin cancer.To evaluate the impact of dermal components on epidermal CPD repair efficiency and to investigate potential factors responsible for the dermal-epidermal crosstalk modulating UVR-induced DNA damage repair in keratinocytes.A model of self-assembled tissue-engineered skin containing human primary keratinocytes and fibroblasts was used in this study.We showed that CPD repair in keratinocytes is positively influenced by the presence of a dermis. We investigated the secretome and found that the cytokine CXCL5 is virtually absent from the culture medium of reconstructed skin, compared with media from fibroblasts and keratinocytes alone. By modulating CXCL5 levels in culture media of keratinocytes, we have shown that CXCL5 is an inhibitor of CPD repair.This work outlines the impact of the secreted dermal components on epidermal UVR-induced DNA damage repair and sheds light on a novel role of CXCL5 in CPD repair.
IL-6 blockade reverses bone marrow failure induced by human acute myeloid leukemia
Authors: Tian Yi Zhang, Ritika Dutta, Brooks Benard, Feifei Zhao, Raymond Yin, Ravindra Majeti
Journal: Science Translational Medicine (2020)

Acute myeloid leukemia inhibits normal erythroid differentiation through paracrine effects of IL-6.
PRN1008, a Reversible Covalent BTK Inhibitor in Clinical Development for Immune Thrombocytopenic Purpura
Authors: Claire L Langrish, J Michael Bradshaw, Timothy D Owens, Robert L Campbell, Michelle R Francesco, Dane E Karr, Steve K Murray, Robert C Quesenberry, Patrick F Smith, Michael D. Taylor, Jiang Zhu, Philip A Nunn, Steven G Gourlay
Journal: Blood (2017)
Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Japan
Authors: Haruka Sakamoto, Masahiro Ishikane, Peter Ueda
Journal: JAMA (2020)

This study uses data from the National Institutes of Infectious Diseases Japan to compare weekly influenza activity in the 2019/2020 vs the 2014-2019 seasons given mitigation strategies taken in 2020 to limit the spread of COVID-19.
Abstract 11853: Cardiovascular Adverse Events Associated With First, Second and Third Generation Tyrosine Kinase Inhibitors Used in Treatment of Chronic Myeloid Leukemia
Authors: Hetavi Mahida, Bharatsinh Gharia, Nene ugoeke, Obiora Maludum, Arif Asif, Dawn Calderon
Journal: Circulation (2018)

Introduction: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplastic disorder, with excess production and proliferation of granulocytes. Tyrosine kinase inhibitors are used for the treat...
Fewer Guns, Ergo Fewer Deaths
Authors: Jerome P. Kassirer
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)
Authors: James M. Sanders, Marguerite L. Monogue, Tomasz Z. Jodlowski, James B. Cutrell
Journal: JAMA (2020)

<h3>Importance</h3> The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. <h3>Observations</h3> No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. <h3>Conclusions and Relevance</h3> The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.
Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study
Authors: Dmitriy Zamarin, Robert A. Burger, Michael W. Sill, Daniel J. Powell, Heather A. Lankes, Michael D. Feldman, Oliver Zivanovic, Camille Gunderson, Emily Ko, Cara Mathews, Sudarshan Sharma, Andrea R. Hagemann, Samir Khleif, Carol Aghajanian
Journal: Journal of Clinical Oncology (2020)

Single-agent PD-1 blockade exhibits limited efficacy in epithelial ovarian cancer (EOC). We evaluated ipilimumab plus nivolumab compared with nivolumab alone in women with persistent or recurrent EOC.Eligibility criteria included measurable disease, 1-3 prior regimens, and platinum-free interval (PFI) < 12 months. Participants were randomly allocated to intravenous nivolumab (every 2 weeks) or induction with nivolumab plus ipilimumab for 4 doses (every 3 weeks), followed by every-2-week maintenance nivolumab for a maximum of 42 doses. The primary null hypothesis was equal probability of objective response within 6 months of random allocation in each arm.One hundred patients were allocated to receive either nivolumab (n = 49), or nivolumab plus ipilimumab (n = 51), with PFI of < 6 months in 62%. Six (12.2%) responses occurred within 6 months in the nivolumab group and 16 (31.4%) in the nivolumab plus ipilimumab group (odds ratio, 3.28; 85% CI, 1.54 to infinity; P = .034). The median progression-free survival (PFS) was 2 and 3.9 months in the nivolumab and nivolumab plus ipilimumab groups, respectively, with a PFI-stratified hazard ratio of 0.53 (95% CI, 0.34 to 0.82); the respective hazard ratio for death was 0.79 (95% CI, 0.44 to 1.42). Grade ≥ 3 related adverse events occurred in 33% of patients in the nivolumab group and 49% in the combination group, with no treatment-related deaths. PD-L1 expression was not significantly associated with response in either treatment group.Compared with nivolumab alone, the combination of nivolumab and ipilimumab in EOC resulted in superior response rate and longer, albeit limited, PFS, with toxicity of the combination regimen comparable to prior reports. Additional combination studies to enhance durability of the dual regimen are warranted.
COVID-19 brings drug development to a halt
Authors: Asher Mullard
Journal: Nature Reviews Drug Discovery (2020)

As the COVID-19 drug pipeline explodes, a fragmented approach to coronavirus drug development risks compromising the potential evidence base.Researchers have already opened over 180 clinical trials of potential COVID-19 treatments for recruitment, and nearly 150 could start soon.An analysis of some of these trials by The Centre for Evidence-Based Medicine shows that interventional products span everything from repurposed antivirals and anti-inflammatory agents to cell therapies and traditional Chinese medicines.And a systematic review of the currently ongoing trials, published on medRχiv, cautions that the poor methodological quality, small sample sizes and long execution time of currently registered trials could compromise the collection of high-quality clinical evidence.Zhi Hong, CEO of Brii Biosciences and former head of infectious disease research at GlaxoSmithKline, is amongst those who
The neonatal microenvironment programs innate γδ T cells through the transcription factor STAT5
Authors: Darshana Kadekar, Rasmus Agerholm, John Rizk, Heidi A. Neubauer, Tobias Suske, Barbara Maurer, Monica Torrellas Viñals, Elena M. Comelli, Amel Taibi, Richard Moriggl, Vasileios Bekiaris
Journal: Journal of Clinical Investigation (2020)

IL-17-producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid-dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive STAT5 mutant mice showed that the STAT5A homolog had a dominant role over STAT5B in promoting γδT17 cell expansion and downregulating gut-associated T-bet. In contrast, STAT5B preferentially expanded IFN-γ-producing γδ populations, implying a previously unknown differential role of STAT5 gene products in lymphocyte lineage regulation. Importantly, mice lacking γδT17 cells as a result of STAT5 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify that the neonatal microenvironment in combination with STAT5 is critical for post-thymic γδT17 development and tissue-specific imprinting, which is essential for infection and autoimmunity.
Abstract 15098: Redefining Normal Resting Heart Rate Values Using Big Data
Authors: Robert Avram, Peter Kuhar, Eric Vittinghoff, Kirstin Aschbacher, Geoff Tison, Mark Pletcher, Greg Marcus, Jeffrey Olgin
Journal: Circulation (2018)

Introduction: Heart rate (HR) is a key cardiovascular vital sign. Clinicians currently use normal values, without consideration of age, that are derived from small-scale observational studies and e...
A cluster of the Corona Virus Disease 2019 caused by incubation period transmission in Wuxi, China
Authors: Yumeng Gao, Chao Shi, Yujun Chen, Ping Shi, Juan Liu, Yong Xiao, Yuan Shen, Enping Chen
Journal: Journal of Infection (2020)

•The cluster's source was the first-generation, who contacted with Wuhan people during the annual meeting from January 15 to 16.•This cluster involved four generations of cases, each of which was transmitted to the next generation during the incubation period.•It was contagious 9 days before the onset of illness.•Two patients in this cluster were tested positive for the nucleic acid of the COVID-19 virus again during isolation and observation after discharge. BackgroundThe infectivity and transmission capacity of COVID-2019 cases during the incubation period are not very clear. The manuscript described a cluster to provide information for research on incubation period infection.MethodsWe collected the required data from "Public Health Emergency Reporting Management Information System", epidemiological questionnaires for the cases, and laboratories.ResultsThe cluster involved four generations, each of which was transmitted to the next generation during the incubation period. The time was 2–7 days, 6–7days, 3–8 days and 9 days prior to onset. As of March 11, the fourth-generation cases had no symptoms. Combined with the epidemiological data, we inferred that the source of the cluster was caused by the first-generation, who contacted with more than ten Wuhan people during the annual meeting from January 15 to 16. Two cases in this cluster were tested positive again during isolation and observation after discharge.ConclusionsWe determined incubation period was infectious, and confirmed that it was contagious 9 days before the onset. The patients who were discharged might need to be observed for a period of time. This study was useful for the practical work, such as in the investigation of close contacts. The infectivity and transmission capacity of COVID-2019 cases during the incubation period are not very clear. The manuscript described a cluster to provide information for research on incubation period infection. We collected the required data from "Public Health Emergency Reporting Management Information System", epidemiological questionnaires for the cases, and laboratories. The cluster involved four generations, each of which was transmitted to the next generation during the incubation period. The time was 2–7 days, 6–7days, 3–8 days and 9 days prior to onset. As of March 11, the fourth-generation cases had no symptoms. Combined with the epidemiological data, we inferred that the source of the cluster was caused by the first-generation, who contacted with more than ten Wuhan people during the annual meeting from January 15 to 16. Two cases in this cluster were tested positive again during isolation and observation after discharge. We determined incubation period was infectious, and confirmed that it was contagious 9 days before the onset. The patients who were discharged might need to be observed for a period of time. This study was useful for the practical work, such as in the investigation of close contacts.
TAK-243, a Small Molecule Inhibitor of Ubiquitin-Activating Enzyme (UAE), Induces ER Stress and Apoptosis in Diffuse Large B-Cell Lymphoma (DLBCL) Cells
Authors: Scott R Best, Cody Paiva, Taylor Rowland, Bhargava Sreekantham, Stephen E Spurgeon, Allison Berger, Alexey Danilov
Journal: Blood (2017)
Investigation of human trophoblast invasion <i>in vitro</i>
Authors: Yassen Abbas, Margherita Y Turco, Graham J Burton, Ashley Moffett
Journal: Human Reproduction Update (2020)

In humans, inadequate trophoblast invasion into the decidua is associated with the 'great obstetrical syndromes' which include pre-eclampsia, foetal growth restriction (FGR) and stillbirth. The mechanisms regulating invasion remain poorly understood, although interactions with the uterine environment are clearly of central importance. Extravillous trophoblast (EVT) cells invade the uterus and transform the spiral arteries. Progress in understanding how they invade has been limited due to the lack of good in vitro models. Firstly, there are no non-malignant cell lines that have an EVT phenotype. Secondly, the invasion assays used are of limited use for the small numbers of primary EVT available from first-trimester placentas. We discuss recent progress in this field with the generation of new EVT lines and invasion assays using microfluidic technology.
Collagen-binding IL-12 enhances tumour inflammation and drives the complete remission of established immunologically cold mouse tumours
Authors: Aslan Mansurov, Jun Ishihara, Peyman Hosseinchi, Lambert Potin, Tiffany M. Marchell, Ako Ishihara, John-Michael Williford, Aaron T. Alpar, Michal M. Raczy, Laura T. Gray, Melody A. Swartz, Jeffrey A. Hubbell
Journal: Nature Biomedical Engineering (2020)
Rationalizations primarily serve reputation management, not decision making
Authors: Sacha Altay, Hugo Mercier
Journal: Behavioral and Brain Sciences (2020)

Abstract We agree with Cushman that rationalizations are the product of biological adaptations, but we disagree about their function. The data available do not show that rationalizations allow us to reason better and make better decisions. The data suggest instead that rationalizations serve reputation management goals, and that they affect our behaviors because we are held accountable by our peers.
Art in Endoscopy: “Alien”
Authors: Roland de Vries
Journal: Endoscopy (2020)

Two tubular adenomas were encountered very close to each other in the sigmoid colon. In order to perform endoscopic mucosal resection with both polyps being removed in just one piece, the submucosal layer was injected with indigo carmine. The two polyps resembled the eyes of an alien just peeking around the corner.
Characteristics of Health Care Personnel with COVID-19 — United States, February 12–April 9, 2020
Authors: Sherry L. Burrer, Marie A. de Perio, Michelle M. Hughes, David T. Kuhar, Sara E. Luckhaupt, Clinton J. McDaniel, Rachael M. Porter, Benjamin Silk, Matthew J. Stuckey, Maroya Walters
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

the coronavirus disease 2019 (COVID-19) pandemic had resulted in 1,521,252 cases and 92,798 deaths worldwide, including 459,165 cases and 16,570 deaths in the United States (1,2).Health care personnel (HCP) are essential workers defined as paid and unpaid persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials (3).During February 12-April 9, among 315,531 COVID-19 cases reported to CDC using a standardized form, 49,370 (16%) included data on whether the patient was a health care worker in the United States; including 9,282 (19%) who were identified as HCP.Among HCP patients with data available, the median age was 42 years (interquartile range [IQR] = 32-54 years), 6,603 (73%) were female, and 1,779 (38%) reported at least one underlying health condition.Among HCP patients with data on health care, household, and community exposures, 780 (55%) reported contact with a COVID-19 patient only in health care settings.Although 4,336 (92%) HCP patients reported having at least one symptom among fever, cough, or shortness of breath, the remaining 8% did not report any of these symptoms.Most HCP with COVID-19 (6,760, 90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups; deaths most frequently occurred in HCP aged ≥65 years.These preliminary findings highlight that whether HCP acquire infection at work or in the community, it is necessary to protect the health and safety of this essential national workforce.Data from laboratory-confirmed COVID-19 cases voluntarily reported to CDC from 50 states, four U.S. territories and affiliated islands, and the District of Columbia, during February 12-April 9 were analyzed.Cases among persons repatriated to the United States from Wuhan, China, and the Diamond Princess cruise ship during January and February were excluded.Public health departments report COVID-19 cases to CDC using a standardized case report form* that collects information on patient demographics, whether the patient is a U.S. health care worker, symptom onset date, specimen collection dates, history of exposures in the 14 days preceding illness onset, COVID-19 symptomology, preexisting medical conditions, and patient outcomes, including
QUANTITATIVE RELATIONSHIP BETWEEN CORONARY CALCIUM SCORE AND HYPERAEMIC MYOCARDIAL BLOOD FLOW AS ASSESSED BY HYBRID [15O]PET/CT IMAGING IN PATIENTS EVALUATED FOR CORONARY ARTERY DISEASE
Authors: Ibrahim Danad, Pieter G. Raijmakers, Yolande E. Appelman, Hans J. Harms, Stefan de Haan, Mijntje L.P. van den Oever, Cornelis van Kuijk, Cornelis P. Allaart, Otto S. Hoekstra, Adriaan A. Lammertsma, Mark Lubberink, Albert C. van Rossum, Paul Knaapen
Journal: Journal of the American College of Cardiology (2011)
Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury
Authors: Elke Ydens, Lukas Amann, Bob Asselbergh, Charlotte L. Scott, Liesbet Martens, Dorine Sichien, Omar Mossad, Thomas Blank, Sofie De Prijck, Donovan Low, Takahiro Masuda, Yvan Saeys, Vincent Timmerman, Ralf Stumm, Florent Ginhoux, Marco Prinz, Sophie Janssens, Martin Guilliams
Journal: Nature Neuroscience (2020)
Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment
Authors: Dörthe Seidel, Stephan Diedrich, Florian Herrle, Henryk Thielemann, Frank Marusch, Rebekka Schirren, Recca Talaulicar, Tobias Gehrig, Nadja Lehwald-Tywuschik, Matthias Glanemann, Jörg Bunse, Martin Hüttemann, Chris Braumann, Oleg Heizmann, Marc Miserez, Thomas Krönert, Stephan Gretschel, Rolf Lefering
Journal: JAMA Surgery (2020)

Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI).To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice.The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population.Negative pressure wound therapy and conventional wound treatment (CWT).The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction.Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35).Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs.ClinicalTrials.gov Identifier: NCT01528033.