tbuckley/cabot-search huggingface dataset:
Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell–Level PI3K Pathway Activation
Authors: Konrad H. Stopsack, Ying Huang, Svitlana Tyekucheva, Travis A. Gerke, Clyde Bango, Habiba Elfandy, Michaela Bowden, Kathryn L. Penney, Thomas M. Roberts, Giovanni Parmigiani, Philip W. Kantoff, Lorelei A. Mucci, Massimo Loda
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Identifying cancers with high PI3K pathway activity is critical for treatment selection and eligibility into clinical trials of PI3K inhibitors. Assessments of tumor signaling pathway activity need to consider intratumoral heterogeneity and multiple regulatory nodes. Experimental Design: We established a novel, mechanistically informed approach to assessing tumor signaling pathways by quantifying single-cell–level multiplex immunofluorescence using custom algorithms. In a proof-of-concept study, we stained archival formalin-fixed, paraffin-embedded (FFPE) tissue from patients with primary prostate cancer in two prospective cohort studies, the Health Professionals Follow-up Study and the Physicians’ Health Study. PTEN, stathmin, and phospho-S6 were quantified on 14 tissue microarrays as indicators of PI3K activation to derive cell-level PI3K scores. Results: In 1,001 men, 988,254 tumor cells were assessed (median, 743 per tumor; interquartile range, 290–1,377). PI3K scores were higher in tumors with PTEN loss scored by a pathologist, higher Gleason grade, and a new, validated bulk PI3K transcriptional signature. Unsupervised machine-learning approaches resulted in similar clustering. Within-tumor heterogeneity in cell-level PI3K scores was high. During long-term follow-up (median, 15.3 years), rates of progression to metastases and death from prostate cancer were twice as high in the highest quartile of PI3K activation compared with the lowest quartile (hazard ratio, 2.04; 95% confidence interval, 1.13–3.68). Conclusions: Our novel pathway-focused approach to quantifying single-cell–level immunofluorescence in FFPE tissue identifies prostate tumors with PI3K pathway activation that are more aggressive and may respond to pathway inhibitors.
Let pharmacists make minor substitutions in event of drug shortages, say stakeholders
Authors: Clare Dyer
Journal: BMJ (2020)

Let pharmacists make minor substitutions in event of drug shortages, say stakeholders Clare DyerGroups representing doctors, pharmacists, and patients have written to England's health and social care secretary, Matt Hancock, calling for community pharmacists to be allowed to make minor substitutions for a GP's prescription in the event of drug shortages, particularly at the end of the transition period for Brexit.
Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial
Authors: Sylvie Bonvalot, Alessandro Gronchi, Cécile Le Péchoux, Carol J Swallow, Dirk Strauss, Pierre Meeus, Frits van Coevorden, Stephan Stoldt, Eberhard Stoeckle, Piotr Rutkowski, Marco Rastrelli, Chandrajit P Raut, Daphne Hompes, Antonino De Paoli, Claudia Sangalli, Charles Honoré, Peter Chung, Aisha Miah, Jean Yves Blay, Marco Fiore, Jean-Jacques Stelmes, Angelo P Dei Tos, Elizabeth H Baldini, Saskia Litière, Sandrine Marreaud, Hans Gelderblom, Rick L Haas
Journal: The Lancet Oncology (2020)
Sox17 Controls Emergence and Remodeling of Nestin-Expressing Coronary Vessels
Authors: Sara González-Hernández, Manuel J. Gómez, Fátima Sánchez-Cabo, Simón Méndez-Ferrer, Pura Muñoz-Cánoves, Joan Isern
Journal: Circulation Research (2020)

Rationale: The molecular mechanisms underlying the formation of coronary arteries during development and during cardiac neovascularization after injury are poorly understood. However, a detailed description of the relevant signaling pathways and functional TFs (transcription factors) regulating these processes is still incomplete. Objective: The goal of this study is to identify novel cardiac transcriptional mechanisms of coronary angiogenesis and vessel remodeling by defining the molecular signatures of coronary vascular endothelial cells during these complex processes. Methods and Results: We demonstrate that Nes-gfp and Nes-CreER T2 transgenic mouse lines are novel tools for studying the emergence of coronary endothelium and targeting sprouting coronary vessels (but not ventricular endocardium) during development. Furthermore, we identify Sox17 as a critical TF upregulated during the sprouting and remodeling of coronary vessels, visualized by a specific neural enhancer from the Nestin gene that is strongly induced in developing arterioles. Functionally, genetic-inducible endothelial deletion of Sox17 causes deficient cardiac remodeling of coronary vessels, resulting in improper coronary artery formation. Conclusions: We demonstrated that Sox17 TF regulates the transcriptional activation of Nestin ’s enhancer in developing coronary vessels while its genetic deletion leads to inadequate coronary artery formation. These findings identify Sox17 as a critical regulator for the remodeling of coronary vessels in the developing heart.
A single-centre observational cohort study to evaluate volume and severity of emergency general surgery admissions during the COVID-19 pandemic: Is there a “lockdown” effect?
Authors: Ross C. McLean, John Young, Aya Musbahi, Jing Xian Lee, Hena Hidayat, Nagi Abdalla, Sabyasachi Chowdhury, Elizabeth A. Baker, Kevin Jon Etherson
Journal: International Journal of Surgery (2020)
Risk of Bias Assessments and Evidence Syntheses for Observational Epidemiologic Studies of Environmental and Occupational Exposures: Strengths and Limitations
Authors: Kyle Steenland, M.K. Schubauer-Berigan, R. Vermeulen, R.M. Lunn, K. Straif, S. Zahm, P. Stewart, W.D. Arroyave, S.S. Mehta, N. Pearce
Journal: Environmental Health Perspectives (2020)

BACKGROUND: Increasingly, risk of bias tools are used to evaluate epidemiologic studies as part of evidence synthesis (evidence integration), often involving meta-analyses.Some of these tools consider hypothetical randomized controlled trials (RCTs) as gold standards.METHODS: We review the strengths and limitations of risk of bias assessments, in particular, for reviews of observational studies of environmental exposures, and we also comment more generally on methods of evidence synthesis.RESULTS: Although RCTs may provide a useful starting point to think about bias, they do not provide a gold standard for environmental studies.Observational studies should not be considered inherently biased vs. a hypothetical RCT.Rather than a checklist approach when evaluating individual studies using risk of bias tools, we call for identifying and quantifying possible biases, their direction, and their impacts on parameter estimates.As is recognized in many guidelines, evidence synthesis requires a broader approach than simply evaluating risk of bias in individual studies followed by synthesis of studies judged unbiased, or with studies given more weight if judged less biased.It should include the use of classical considerations for judging causality in human studies, as well as triangulation and integration of animal and mechanistic data.CONCLUSIONS: Bias assessments are important in evidence synthesis, but we argue they can and should be improved to address the concerns we raise here.Simplistic, mechanical approaches to risk of bias assessments, which may particularly occur when these tools are used by nonexperts, can result in erroneous conclusions and sometimes may be used to dismiss important evidence.Evidence synthesis requires a broad approach that goes beyond assessing bias in individual human studies and then including a narrow range of human studies judged to be unbiased in evidence synthesis.
Characterization and management of hypertrichosis induced by low-dose oral minoxidil in the treatment of hair loss
Authors: Juan Jimenez-Cauhe, David Saceda-Corralo, Rita Rodrigues-Barata, Angela Hermosa-Gelbard, Oscar M. Moreno-Arrones, Rocio Gil-Redondo, Daniel Ortega-Quijano, Diego Fernandez-Nieto, Pedro Jaen-Olasolo, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2020)
Pharmacological Treatments for Tinnitus—Reply
Authors: Jay F. Piccirillo, Thomas L. Rodebaugh, Eric J. Lenze
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
An invited commentary on “Does the intermittent pringle's maneuver lose its clinical value in reducing bleeding during hepatectomy? A systematic review and meta-analysis” (International Journal of Surgery 2020 Epub ahead of print) Is there still a role for the intermittent pringle maneuver during hepatic resections?
Authors: Glenn K. Wakam, Hasan B. Alam
Journal: International Journal of Surgery (2020)
Seasonal coronavirus protective immunity is short-lasting
Authors: Arthur W. D. Edridge, Joanna Kaczorowska, Alexis C. R. Hoste, Margreet Bakker, Michelle Klein, Katherine Loens, Maarten F. Jebbink, Amy Matser, Cormac M. Kinsella, Paloma Rueda, Margareta Ieven, Herman Goossens, Maria Prins, Patricia Sastre, Martin Deijs, Lia van der Hoek
Journal: Nature Medicine (2020)

A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.
Low-Density Lipoprotein Cholesterol and Adverse Cardiovascular Events After Percutaneous Coronary Intervention
Authors: Maneesh Sud, Lu Han, Maria Koh, Husam Abdel-Qadir, Peter C. Austin, Michael E. Farkouh, Lucas C. Godoy, Patrick R. Lawler, Jacob A. Udell, Harindra C. Wijeysundera, Dennis T. Ko
Journal: Journal of the American College of Cardiology (2020)
Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19
Authors: Coraline Radermecker, Nancy Detrembleur, Julien Guiot, Etienne Cavalier, Monique Henket, Céline d’Emal, Céline Vanwinge, Didier Cataldo, Cécile Oury, Philippe Delvenne, Thomas Marichal
Journal: The Journal of Experimental Medicine (2020)

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease–19 (COVID-19). While SARS-CoV-2–triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis. However, whether NETs infiltrate particular compartments in severe COVID-19 lungs remains to be clarified. Here we analyzed postmortem lung specimens from four patients who succumbed to COVID-19 and four patients who died from a COVID-19–unrelated cause. We report the presence of NETs in the lungs of each COVID-19 patient. NETs were found in the airway compartment and neutrophil-rich inflammatory areas of the interstitium, while NET-prone primed neutrophils were present in arteriolar microthrombi. Our results support the hypothesis that NETs may represent drivers of severe pulmonary complications of COVID-19 and suggest that NET-targeting approaches could be considered for the treatment of uncontrolled tissue-damaging and thrombotic responses in COVID-19.
Sports-related injuries and illnesses in Paralympic athletes (PhD Academy Award)
Authors: Kristina Fagher
Journal: British Journal of Sports Medicine (2020)

The aim of my thesis was to gain an in-depth understanding of the epidemiology and data collection methods of sports injuries and illnesses in Paralympic sport to assist the development of evidence-based preventive measures. To do this, I combined holistic approaches including athletes’ voices with empirical and systematic ones.1

The interest of Paralympic sport is steadily increasing. There is, however, limited knowledge of the epidemiology of injuries and illnesses,2 and data collection methods have not been adapted for Paralympic athletes.

To gain greater knowledge, I conducted five studies in a stepwise progression.

1.  First, a qualitative study concerning Paralympic athletes’ perceptions of experiences of injuries was conducted.3

2.  Based on this, I formulated a study protocol to improve epidemiological data collection.4

3.  To ensure accessibility and validity of …
Bats and viruses
Authors: Vikram Misra
Journal: The Lancet Infectious Diseases (2020)

The isolation of Hendra and Nipah viruses from bats in the vicinity of the outbreaks, and the subsequent detection of coronaviruses similar to the severe acute respiratory syndrome coronavirus from various bat species, led to speculation that bats may be reservoirs for potentially zoonotic viruses. These events stimulated a global search for bat viruses that resulted in the detection and sometimes isolation of over 200 viruses from almost all viral families. These observations suggested that bats may harbour a substantial diversity of viruses rivalling or surpassing that in rodents.
A call to standardize the BCC:SCC ratio
Authors: Z. Jiyad, L. Marquart, A.C. Green
Journal: British Journal of Dermatology (2020)

Basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC) are the two commonest cancers in white populations worldwide. While sharing some features, they are distinct clinically and pathologically and thus the ratio of BCC to SCC incidence rates serves as a useful composite that enables immediate comparisons of trends within and between populations. There is a widely held belief that the BCC:SCC ratio sits relatively constantly at around 4:1 in the general population, though this belief has little apparent basis.
β2‐adrenergic agonists do not improve physical performance in healthy individuals
Authors: Ana Cardoso, Beatriz Mónico, Jorge M. R. Gama, Henrique P. Neiva, Daniel A. Marinho, Olga Lourenço
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Percutaneous endoscopic removal of a biliary metal stent retained in the jejunum using a digital cholangioscope
Authors: Shuntaro Mukai, Takao Itoi, Atsushi Sofuni, Takayoshi Tsuchiya, Kentaro Ishii, Reina Tanaka, Ryosuke Tonozuka
Journal: Endoscopy (2020)

Temporary placement of a biliary metal stent is a useful percutaneous treatment for benign hepaticojejunal anastomotic stricture [1] [2] [3] [4]. However, a metal stent that has been placed will sometimes migrate spontaneously and can be retained in the jejunum. Endoscopic removal of a migrated metal stent retained in the jejunum is sometimes technically challenging and, in difficult cases, invasive surgical removal is required. Here, we describe the successful non-invasive endoscopic removal of a retained metal stent using a digital cholangioscope that was passed via the percutaneous fistula created by a percutaneous transhepatic biliary drain.
IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis
Authors: Kongyang Ma, Wenhan Du, Fan Xiao, Man Han, Enyu Huang, Na Peng, Yuan Tang, Chong Deng, Lixiong Liu, Yulan Chen, Jingjing Li, Shiwen Yuan, Qin Huang, Xiaoping Hong, Dajun Hu, Xiaoyan Cai, Quan Jiang, Dongzhou Liu, Liwei Lu
Journal: Cellular and Molecular Immunology (2020)
1,1-Bis(3’-indolyl)-1-(p-tbutylphenyl)methane inhibits ovarian cancer cell growth through PPARγ- dependent and -independent pathways
Authors: Ping Lei, Maen Abdelrahim, Stephen Safe
Journal: Cancer Research (2006)

3822  1,1-Bis(3’-indolyl)-1-(p-tbutylphenyl)methane (DIM-C-pPhtBu) is a novel methylene-substituted diindolymethane (C-DIM) compound that exhibits a broad spectrum of anticancer activities. Previous studies have shown that C-DIMs activate peroxisome proliferator-activated receptor gamma (PPARγ) in colon, pancreatic and breast cancer cell lines. In this study, we have investigated the mechanism of action of the PPARγ-active DIM-C-pPhtBu in the SKOV-3, PEO1, OVCAR-3 and ES-2 ovarian cancer cell lines. Treatment of SKOV3 ovarian cancer cells with this compound (5 μM) inhibits cell proliferation, whereas up to 15 μM rosiglitazone had no effect on cell growth. DIM-C-pPhtBu also inhibits G0/G1 to S phase cell cycle progression and this is linked, in part, to PPARγ-dependent induction of the cyclin-dependent kinase inhibitor p21. DIM-C-pPhtBu induces PPARγ-independent downregulation of cyclin D1 and we therefore further investigated activation of receptor-independent pathways. DIM-C-pPhtBu also induced apoptosis in SKOV3 cells and this was related to induction of glucose related protein 78 (GRP78) which is typically upregulated as part of the unfolded protein response during endoplasmic reticulum (ER) stress. Activation of ER stress was also observed in other ovarian cancer cell lines treated with DIM-C-pPhtBu. In addition, DIM-C-pPhtBu coordinately induced C/EBP homologous protein (CHOP) which in turn activated death receptor 5 (DR5) and the extrinsic pathway of apoptosis. Furthermore, c-Jun N-terminal kinase (JNK), another modulator of extrinsic apoptosis pathway, was also induced after 2 hours treatment with 15 μM compound. These results demonstrate that DIM-C-pPhtBu inhibits growth and induced apoptosis in ovarian cancer cells through both PPARγ-dependent and -independent pathways and the dual mechanism of action will be advantageous for future clinical development of these compounds for treatment of ovarian cancer.
Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study
Authors: Karim Fizazi, Gero Kramer, Jean-Christophe Eymard, Cora N Sternberg, Johann de Bono, Daniel Castellano, Bertrand Tombal, Christian Wülfing, Michael Liontos, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Ásgerður Sverrisdóttir, Christine Theodore, Susan Feyerabend, Carole Helissey, Stéphane Oudard, Gaetano Facchini, Elizabeth M Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Samira Bensfia, Ronald de Wit
Journal: The Lancet Oncology (2020)
Author Correction: Exploring the coronavirus pandemic with the WashU Virus Genome Browser
Authors: Jennifer A. Flynn, Deepak Purushotham, Mayank N. K. Choudhary, Xiaoyu Zhuo, Changxu Fan, Gavriel Matt, Daofeng Li, Ting Wang
Journal: Nature Genetics (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Integrative Benchmarking to Advance Neurally Mechanistic Models of Human Intelligence
Authors: Martin Schrimpf, Jonas Kubilius, Michael J. Lee, N. Apurva Ratan Murty, Robert Ajemian, James J. DiCarlo
Journal: Neuron (2020)

A potentially organizing goal of the brain and cognitive sciences is to accurately explain domains of human intelligence as executable, neurally mechanistic models. Years of research have led to models that capture experimental results in individual behavioral tasks and individual brain regions. We here advocate for taking the next step: integrating experimental results from many laboratories into suites of benchmarks that, when considered together, push mechanistic models toward explaining entire domains of intelligence, such as vision, language, and motor control. Given recent successes of neurally mechanistic models and the surging availability of neural, anatomical, and behavioral data, we believe that now is the time to create integrative benchmarking platforms that incentivize ambitious, unified models. This perspective discusses the advantages and the challenges of this approach and proposes specific steps to achieve this goal in the domain of visual intelligence with the case study of an integrative benchmarking platform called Brain-Score.
Effect of the COVID-19 pandemic on viral hepatitis services in sub-Saharan Africa
Authors: Maud Lemoine, Jin Un Kim, Gibril Ndow, Sulayman Bah, Karen Forrest, John Rwegasha, Marielle Bouyou, Delphine Napon, Sosthene Somda, Appolinaire Sawadogo, Roger Sombie, Yusuke Shimakawa
Journal: The Lancet. Gastroenterology & hepatology (2020)
Bridging the Gap at Warp Speed — Delivering Options for Preventing and Treating Covid-19
Authors: Moncef Slaoui, Shannon E. Greene, Janet Woodcock
Journal: New England Journal of Medicine (2020)

Bridging the Gap at Warp Speed In addition to its goal of delivering safe and effective vaccines quickly, Operation Warp Speed aims to combat Covid-19 by improving the use of existing therapies and...
UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma
Authors: Emily S. Reardon, Vivek Shukla, Sichuan Xi, Sudheer K. Gara, Yi Liu, David Straughan, Mary Zhang, Julie A. Hong, Eden C. Payabyab, Anju Kumari, William G. Richards, Assunta De Rienzo, Raffit Hassan, Markku Miettinen, Liqiang Xi, Mark Raffeld, Lisa T. Uechi, Xinmin Li, Ruihong Wang, Haobin Chen, Chuong D. Hoang, Raphael Bueno, David S. Schrump
Journal: Journal of Thoracic Oncology (2020)
SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19
Authors: Lars F. Westblade, Gagandeep Brar, Laura C. Pinheiro, Demetrios Paidoussis, Mangala Rajan, Peter Martin, Parag Goyal, Jorge L. Sepulveda, Lisa Zhang, Gary George, Dakai Liu, Susan Whittier, Markus Plate, Catherine B. Small, Jacob H. Rand, Melissa M. Cushing, Thomas J. Walsh, Joseph Cooke, Monika M. Safford, Massimo Loda, Michael J. Satlin
Journal: Cancer Cell (2020)