tbuckley/cabot-search huggingface dataset:
Rates of Overall Survival and Intracranial Control in the Magnetic Resonance Imaging Era for Patients With Limited-Stage Small Cell Lung Cancer With and Without Prophylactic Cranial Irradiation
Authors: Todd A. Pezzi, Penny Fang, Olsi Gjyshi, Lei Feng, Suyu Liu, Ritsuko Komaki, Steven H. Lin
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Historical data suggest that there is an overall survival benefit associated with prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). However, as the fidelity of magnetic resonance imaging (MRI) of the brain continues to improve, this idea is now being questioned, with recent research showing no survival benefit associated with PCI in extensive-stage SCLC; however, the role for PCI is not clear in patients with limited-stage SCLC (LS-SCLC). <h3>Objective</h3> To report the overall survival and rates of intracranial control for patients with LS-SCLC, all staged with MRI, who either did or did not undergo PCI. <h3>Design, Setting, and Participants</h3> This cohort study included 297 patients with LS-SCLC at a large US academic cancer center. Patients were treated with thoracic radiation; 205 also underwent PCI and 92 did not. All patients underwent at least baseline MRI, with restaging brain MRI and/or computed tomography; they did not have disease progression after thoracic radiation treatment. A propensity score–matching analysis was undertaken in an attempt to adjust for potential bias. Of the 297 patients who met the inclusion criteria, the propensity score was calculated for 295 patients, using patient, tumor, and treatment characteristics. Data were analyzed in October 2019. <h3>Intervention</h3> Prophylactic cranial irradiation in patients with LS-SCLC. <h3>Main Outcomes and Measures</h3> The rate of overall survival and intracranial control. <h3>Results</h3> Of the 297 patients, 162 (54.5%) were men. The median age was 62.2 years (range, 27.0-85.0 years) for patients who underwent PCI and 68.6 years (range, 40.0-86.0 years) for those who did not undergo PCI. The 3-year cumulative incidence rate of brain metastases was higher in the no-PCI group vs the PCI group, when counting death as a competing risk, but the difference was not statistically significant (20.40% [95% CI, 12.45%-29.67%] vs 11.20% [95% CI, 5.40%-19.20%];<i>P</i> = .10). The use of PCI was not associated with a difference in overall survival between the patient groups (hazard ratio, 0.844; 95% CI, 0.604-1.180;<i>P</i> = .32). <h3>Conclusions and Relevance</h3> These findings suggest that patients with LS-SCLC staged with MRI who undergo PCI after thoracic radiation treatment were not associated with a decreased risk of developing new brain metastases compared with patients who do not undergo PCI. The use of PCI was not associated with an overall survival benefit for such patients.
Clinician Burnout and Professional Well-being
Authors: Erin L. Arnold, David H. Sikes, J. Timothy Harrington
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
On-site fabrication of injectable 131I-labeled microgels for local radiotherapy
Authors: Sodam Kim, Sang-Gu Yim, Ajeesh Chandrasekharan, Keum-Yong Seong, Tae Wook Lee, Byeongyeon Kim, Keunyoung Kim, Sungyoung Choi, Seung Yun Yang
Journal: Journal of Controlled Release (2020)
Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process
Authors: Hao Zhang, Zijian Kang, Haiyi Gong, Da Xu, Jing Wang, Zhixiu Li, Zifu Li, Xinggang Cui, Jianru Xiao, Jian Zhan, Tong Meng, Wang Zhou, Jianmin Liu, Huji Xu
Journal: Gut (2020)

Objective Since December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed. Design Five datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion. Results Cell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon. Conclusion This study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.
Psychosocial Stressors at Work and the Risk of Sickness Absence Due to a Diagnosed Mental Disorder
Authors: Caroline S. Duchaine, Karine Aubé, Mahée Gilbert-Ouimet, Michel Vézina, Ruth Ndjaboué, Victoria Massamba, Denis Talbot, Mathilde Lavigne-Robichaud, Xavier Trudel, Ana-Paula Bruno Pena-Gralle, Alain Lesage, Lynne Moore, Alain Milot, Danielle Laurin, Chantal Brisson
Journal: JAMA Psychiatry (2020)

Mental health problems are associated with considerable occupational, medical, social, and economic burdens. Psychosocial stressors at work have been associated with a higher risk of mental disorders, but the risk of sickness absence due to a diagnosed mental disorder, indicating a more severe condition, has never been investigated in a systematic review and meta-analysis.To synthesize the evidence of the association of psychosocial stressors at work with sickness absence due to a diagnosed mental disorder among adult workers.Seven electronic databases (MEDLINE, Embase, PsycInfo, Web of Science, CINAHL, Sociological Abstracts, and International Bibliography of the Social Sciences), 3 gray literature databases (Grey Literature Report, WHO-IRIS and Open Grey), and the reference lists of all eligible studies and reviews were searched in January 2017 and updated in February 2019.Only original prospective studies evaluating the association of at least 1 psychosocial stressor at work from the 3 most recognized theoretical models were eligible: the job demand-control-support model, including exposure to job strain (high psychological demands with low job control); effort-reward imbalance model; and organizational justice model. Study selection was performed in duplicate by blinded independent reviewers. Among the 28 467 citations screened, 23 studies were eligible for systematic review.This meta-analysis followed the PRISMA and MOOSE guidelines. Data extraction and risk of bias evaluation, using the Risk of Bias in Nonrandomized Studies-Interventions tool, were performed in duplicate by blinded independent reviewers. Data were pooled using random-effect models.Sickness absence due to a mental disorder with a diagnosis obtained objectively.A total of 13 studies representing 130 056 participants were included in the 6 meta-analyses. Workers exposed to low reward were associated with a higher risk of sickness absence due to a diagnosed mental disorder compared with nonexposed workers (pooled risk ratio [RR], 1.76 [95% CI, 1.49-2.08]), as were those exposed to effort-reward imbalance (pooled RR, 1.66 [95% CI, 1.37-2.00]), job strain (pooled RR, 1.47 [95% CI, 1.24-1.74]), low job control (pooled RR, 1.25 [95% CI, 1.02-1.53]), and high psychological demands (pooled RR, 1.23 [95% CI, 1.04-1.45]).This meta-analysis found that workers exposed to psychosocial stressors at work were associated with a higher risk of sickness absence due to a mental disorder. A better understanding of the importance of these stressors could help physicians when evaluating their patients' mental health and work capacity.
A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer
Authors: Alex H. Wagner, Brian Walsh, Georgia Mayfield, David Tamborero, Dmitriy Sonkin, Kilannin Krysiak, Jordi Deu-Pons, Ryan P. Duren, Jianjiong Gao, Julie McMurry, Sara Patterson, Catherine del Vecchio Fitz, Beth A. Pitel, Ozman U. Sezerman, Kyle Ellrott, Jeremy L. Warner, Damian T. Rieke, Tero Aittokallio, Ethan Cerami, Deborah I. Ritter, Lynn M. Schriml, Robert R. Freimuth, Melissa Haendel, Gordana Raca, Subha Madhavan, Michael Baudis, Jacques S. Beckmann, Rodrigo Dienstmann, Debyani Chakravarty, Xuan Shirley Li, Susan Mockus, Olivier Elemento, Nikolaus Schultz, Nuria Lopez-Bigas, Mark Lawler, Jeremy Goecks, Malachi Griffith, Obi L. Griffith, Adam A. Margolin
Journal: Nature Genetics (2020)

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.
Adaptive Shifts in Gene Regulation Underlie a Developmental Delay in Thermogenesis in High-Altitude Deer Mice
Authors: Jonathan P Velotta, Cayleih E Robertson, Rena M Schweizer, Grant B McClelland, Zachary A Cheviron
Journal: Molecular Biology and Evolution (2020)

Abstract Aerobic performance is tied to fitness as it influences an animal’s ability to find food, escape predators, or survive extreme conditions. At high altitude, where low O2 availability and persistent cold prevail, maximum metabolic heat production (thermogenesis) is an aerobic performance trait that is closely linked to survival. Understanding how thermogenesis evolves to enhance survival at high altitude will yield insight into the links between physiology, performance, and fitness. Recent work in deer mice (Peromyscus maniculatus) has shown that adult mice native to high altitude have higher thermogenic capacities under hypoxia compared with lowland conspecifics, but that developing high-altitude pups delay the onset of thermogenesis. This finding suggests that natural selection on thermogenic capacity varies across life stages. To determine the mechanistic cause of this ontogenetic delay, we analyzed the transcriptomes of thermoeffector organs—brown adipose tissue and skeletal muscle—in developing deer mice native to low and high altitude. We demonstrate that the developmental delay in thermogenesis is associated with adaptive shifts in the expression of genes involved in nervous system development, fuel/O2 supply, and oxidative metabolism pathways. Our results demonstrate that selection has modified the developmental trajectory of the thermoregulatory system at high altitude and has done so by acting on the regulatory systems that control the maturation of thermoeffector tissues. We suggest that the cold and hypoxic conditions of high altitude force a resource allocation tradeoff, whereby limited energy is allocated to developmental processes such as growth, versus active thermogenesis, during early development.
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Authors: Timothy P. Sheahan, Amy C. Sims, Shuntai Zhou, Rachel L. Graham, Andrea J. Pruijssers, Maria L. Agostini, Sarah R. Leist, Alexandra Schäfer, Kenneth H. Dinnon, Laura J. Stevens, James D. Chappell, Xiaotao Lu, Tia M. Hughes, Amelia S. George, Collin S. Hill, Stephanie A. Montgomery, Ariane J. Brown, Gregory R. Bluemling, Michael G. Natchus, Manohar Saindane, Alexander A. Kolykhalov, George Painter, Jennifer Harcourt, Azaibi Tamin, Natalie J. Thornburg, Ronald Swanstrom, Mark R. Denison, Ralph S. Baric
Journal: Science Translational Medicine (2020)

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Here, we show that the ribonucleoside analog β-d-N
Association Between Medicare Expenditures and Adverse Events for Patients With Acute Myocardial Infarction, Heart Failure, or Pneumonia in the United States
Authors: Yun Wang, Noel Eldridge, Mark L. Metersky, Nancy Sonnenfeld, David Rodrick, Jonathan M. Fine, Sheila Eckenrode, Deron H. Galusha, Anila Tasimi, David R. Hunt, Susannah M. Bernheim, Sharon-Lise T. Normand, Harlan M. Krumholz
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Studies have shown that adverse events are associated with increasing inpatient care expenditures, but contemporary data on the association between expenditures and adverse events beyond inpatient care are limited. <h3>Objective</h3> To evaluate whether hospital-specific adverse event rates are associated with hospital-specific risk-standardized 30-day episode-of-care Medicare expenditures for fee-for-service patients discharged with acute myocardial infarction (AMI), heart failure (HF), or pneumonia. <h3>Design, Setting, and Participants</h3> This cross-sectional study used the 2011 to 2016 hospital-specific risk-standardized 30-day episode-of-care expenditure data from the Centers for Medicare &amp; Medicaid Services and medical record–abstracted in-hospital adverse event data from the Medicare Patient Safety Monitoring System. The setting was acute care hospitals treating at least 25 Medicare fee-for-service patients for AMI, HF, or pneumonia in the United States. Participants were Medicare fee-for-service patients 65 years or older hospitalized for AMI, HF, or pneumonia included in the Medicare Patient Safety Monitoring System in 2011 to 2016. The dates of analysis were July 16, 2017, to May 21, 2018. <h3>Main Outcomes and Measures</h3> Hospitals' risk-standardized 30-day episode-of-care expenditures and the rate of occurrence of adverse events for which patients were at risk. <h3>Results</h3> The final study sample from 2194 unique hospitals included 44 807 patients (26.1% AMI, 35.6% HF, and 38.3% pneumonia) with a mean (SD) age of 79.4 (8.6) years, and 52.0% were women. The patients represented 84 766 exposures for AMI, 96 917 exposures for HF, and 109 641 exposures for pneumonia. Patient characteristics varied by condition but not by expenditure category. The mean (SD) risk-standardized expenditures were $22 985 ($1579) for AMI, $16 020 ($1416) for HF, and $16 355 ($1995) for pneumonia per hospitalization. The mean risk-standardized rates of occurrence of adverse events for which patients were at risk were 3.5% (95% CI, 3.4%-3.6%) for AMI, 2.5% (95% CI, 2.5%-2.5%) for HF, and 3.0% (95% CI, 2.9%-3.0%) for pneumonia. An increase by 1 percentage point in the rate of occurrence of adverse events was associated with an increase in risk-standardized expenditures of $103 (95% CI, $57-$150) for AMI, $100 (95% CI, $29-$172) for HF, and $152 (95% CI, $73-$232) for pneumonia per discharge. <h3>Conclusions and Relevance</h3> Hospitals with high adverse event rates were more likely to have high 30-day episode-of-care Medicare expenditures for patients discharged with AMI, HF, or pneumonia.
All ranitidine should be discarded, says US drug agency
Authors: Owen Dyer
Journal: BMJ (2020)

The heartburn and stomach ulcer drug Zantac (ranitidine) and its generic equivalent should be removed from pharmacy shelves and should be discarded if found at home, the US Food and Drug Administration has said.

The agency cited new findings from its analysis of stockpiled ranitidine, which showed that levels of the probable carcinogen N -nitrosodimethylamine (NDMA) increased over time in the drug during storage.1

New FDA testing, the agency said, had “confirmed …
Combined Cohesin–RUNX1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes
Authors: Yotaro Ochi, Ayana Kon, Toyonori Sakata, Masahiro M Nakagawa, Naotaka Nakazawa, Masanori Kakuta, Keisuke Kataoka, Haruhiko Koseki, Manabu Nakayama, Daisuke Morishita, Tatsuaki Tsuruyama, Ryunosuke Saiki, Akinori Yoda, Rurika Okuda, Tetsuichi Yoshizato, Kenichi Yoshida, Yusuke Shiozawa, Yasuhito Nannya, Shinichi Kotani, Yasunori Kogure, Nobuyuki Kakiuchi, Tomomi Nishimura, Hideki Makishima, Luca Malcovati, Akihiko Yokoyama, Kengo Takeuchi, Eiji Sugihara, Taka-Aki Sato, Masashi Sanada, Akifumi Takaori-Kondo, Mario Cazzola, Mineko Kengaku, Satoru Miyano, Katsuhiko Shirahige, Hiroshi I. Suzuki, Seishi Ogawa
Journal: Cancer Discovery (2020)

STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant comutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between STAG2 and RUNX1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of STAG2 and RUNX1, which colocalize at enhancer-rich, CTCF-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPC) and myelodysplastic syndromes (MDS) in mice. Attenuated enhancer-promoter loops in STAG2/RUNX1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Downregulation of high-pausing genes is also confirmed in STAG2-cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2-RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis. SIGNIFICANCE: We demonstrate a critical role of an interplay between STAG2 and a master transcription factor of hematopoiesis, RUNX1, in MDS development, and further reveal their contribution to regulation of high-order chromatin structures, particularly enhancer-promoter looping, and the link between transcriptional pausing and selective gene dysregulation caused by cohesin deficiency.This article is highlighted in the In This Issue feature, p. 747.
Adaptive guidelines for the treatment of gonorrhea to increase the effective life span of antibiotics among men who have sex with men in the United States: A mathematical modeling study
Authors: Reza Yaesoubi, Ted Cohen, Katherine Hsu, Thomas L. Gift, Harrell Chesson, Joshua A. Salomon, Yonatan H. Grad
Journal: PLoS Medicine (2020)

Background The rise of gonococcal antimicrobial resistance highlights the need for strategies that extend the clinically useful life span of antibiotics. Because there is limited evidence to support the current practice of switching empiric first-line antibiotic when resistance exceeds 5% in the population, our objective was to compare the impact of alternative strategies on the effective life spans of antibiotics and the overall burden of gonorrhea. Methods and findings We developed and calibrated a mathematical model of gonorrhea transmission among men who have sex with men (MSM) in the United States. We calibrated the model to the estimated prevalence of gonorrhea, the rate of gonorrhea cases, and the proportion of cases presenting symptoms among MSM in the US. We used this model to project the effective life span of antibiotics and the number of gonorrhea cases expected under current and alternative surveillance strategies over a 50-year simulation period. We demonstrate that compared to the current practice, a strategy that uses quarterly (as opposed to yearly) surveillance estimates and incorporates both the estimated prevalence of resistance and the trend in the prevalence of resistance to determine treatment guidelines could extend the effective life span of antibiotics by 0.83 years. This is equivalent to successfully treating an additional 80.1 (95% uncertainty interval: [47.7, 111.9]) gonorrhea cases per 100,000 MSM population each year with the first-line antibiotics without worsening the burden of gonorrhea. If the annual number of isolates tested for drug susceptibility is doubled, this strategy could increase the effective life span of antibiotics by 0.94 years, which is equivalent to successfully treating an additional 91.1 (54.3, 127.3) gonorrhea cases per 100,000 MSM population each year without increasing the incidence of gonorrhea. Study limitations include that our conclusions might not be generalizable to other settings because our model describes the transmission of gonorrhea among the US MSM population, and, to better capture uncertainty in the characteristics of current and future antibiotics, we chose to model hypothetical drugs with characteristics similar to the antibiotics commonly used in gonorrhea treatment. Conclusions Our results suggest that use of data from surveillance programs could be expanded to prolong the clinical effectiveness of antibiotics without increasing the burden of the disease. This highlights the importance of maintaining effective surveillance systems and the engagement of policy makers to turn surveillance findings into timely and effective decisions.
The association of broadband internet access with dermatology practitioners: An ecologic study
Authors: Zachary J. Solomon, Vignesh Ramachandran, Taylor P. Kohn, Paige E. Nichols, Nora M. Haney, Hiten D. Patel, Michael H. Johnson, Misha V. Koshelev, Harry Dao
Journal: Journal of the American Academy of Dermatology (2020)