tbuckley/cabot-search huggingface dataset:
Genome-wide association study of preserved ratio impaired spirometry (PRISm)
Authors: Daniel H. Higbee, Alvin Lirio, Fergus Hamilton, Raquel Granell, Annah B. Wyss, Stephanie J. London, Traci M. Bartz, Sina A. Gharib, Michael H. Cho, Emily Wan, Edwin Silverman, James D. Crapo, Jesus V.T. Lominchar, Torben Hansen, Niels Grarup, Thomas Dantoft, Line Kårhus, Allan Linneberg, George T. O'Connor, Josée Dupuis, Hanfie Xu, Maaike M. De Vries, Xiaowei Hu, Stephen S. Rich, R. Graham Barr, Ani Manichaikul, Sara R.A. Wijnant, Guy G. Brusselle, Lies Lahousse, Xuan Li, Ana I. Hernández Cordero, Ma'en Obeidat, Don D. Sin, Sarah E. Harris, Paul Redmond, Adele M. Taylor, Simon R. Cox, Alexander T. Williams, Nick Shrine, Catherine John, Anna L. Guyatt, Ian P. Hall, George Davey Smith, Martin D. Tobin, James W. Dodd
Journal: European Respiratory Journal (2023)

Background Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV 1 ) &lt;80% predicted and FEV 1 /forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. Methods We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. Results 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (r g ) between PRISm and spirometric COPD (r g =0.62, p&lt;0.001) was observed, and genetic correlation with type 2 diabetes (r g =0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. Conclusion This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM ), rs9431040 ( HLX ), rs62018863 ( TMEM114 ) and rs185937162 ( HLA-B ), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.
Learning to live with covid-19: testing, vaccination, and mask wearing still play a key part in managing the pandemic
Authors: Zaki Arshad, Joshua Nazareth, Manish Pareek
Journal: BMJ (2023)

With a fall in covid-19 mortality and hospital admission rates over the past two years, 1 public interest in the pandemic has reduced. 1 2 However, SARS-CoV-2 remains in widespread circulation. 2As we approach winter, a period associated with increased strain on our NHS, what can we expect from the covid-19 pandemic, and how can we prepare?OPINION
Releasable, Immune‐Instructive, Bioinspired Multilayer Coating Resists Implant‐Induced Fibrosis while Accelerating Tissue Repair
Authors: Riki Toita, Masahiro Kitamura, Akira Tsuchiya, Jeong‐Hun Kang, Shinjiro Kasahara
Journal: Advanced Healthcare Materials (2023)

Implantable biomaterials trigger foreign body reactions (FBRs), which reduces the functional life of medical devices and prevents effective tissue regeneration. Although existing therapeutic approaches can circumvent collagen-rich fibrotic encapsulation secondary to FBRs, they disrupt native tissue repair. Herein, a new surface engineering strategy in which an apoptotic-mimetic, immunomodulatory, phosphatidylserine liposome (PSL) is released from an implant coating to induce the formation of a macrophage phenotype that mitigates FBRs and improves tissue healing is described. PSL-multilayers constructed on implant surfaces via the layer-by-layer method release PSLs over a 1-month period. In rat muscles, poly(etheretherketone) (PEEK), a nondegradable polymer implant model, induces FBRs with dense fibrotic scarring under an aberrant cellular profile that recruits high levels of inflammatory infiltrates, foreign body giant cells (FBGCs), scar-forming myofibroblasts, and inflammatory M1-like macrophages but negligible amounts of anti-inflammatory M2-like phenotypes. However, the PSL-multilayer coating markedly diminishes these detrimental signatures by shifting the macrophage phenotype. Unlike other therapeutics, PSL-multilayered coatings also stimulate muscle regeneration. This study demonstrates that PSL-multilayered coatings are effective in eliminating FBRs and promoting regeneration, hence offering potent and broad applications for implantable biomaterials.
Neighborhood-Level Socioeconomic Status and Prescription Fill Patterns Among Patients With Heart Failure
Authors: Amrita Mukhopadhyay, Saul Blecker, Xiyue Li, Ian M. Kronish, Rumi Chunara, Yaguang Zheng, Steven Lawrence, John A. Dodson, Sam Kozloff, Samrachana Adhikari
Journal: JAMA Network Open (2023)

Importance Medication nonadherence is common among patients with heart failure with reduced ejection fraction (HFrEF) and can lead to increased hospitalization and mortality. Patients living in socioeconomically disadvantaged areas may be at greater risk for medication nonadherence due to barriers such as lower access to transportation or pharmacies. Objective To examine the association between neighborhood-level socioeconomic status (nSES) and medication nonadherence among patients with HFrEF and to assess the mediating roles of access to transportation, walkability, and pharmacy density. Design, Setting, and Participants This retrospective cohort study was conducted between June 30, 2020, and December 31, 2021, at a large health system based primarily in New York City and surrounding areas. Adult patients with a diagnosis of HF, reduced EF on echocardiogram, and a prescription of at least 1 guideline-directed medical therapy (GDMT) for HFrEF were included. Exposure Patient addresses were geocoded, and nSES was calculated using the Agency for Healthcare Research and Quality SES index, which combines census-tract level measures of poverty, rent burden, unemployment, crowding, home value, and education, with higher values indicating higher nSES. Main Outcomes and Measures Medication nonadherence was obtained through linkage of health record prescription data with pharmacy fill data and was defined as proportion of days covered (PDC) of less than 80% over 6 months, averaged across GDMT medications. Results Among 6247 patients, the mean (SD) age was 73 (14) years, and majority were male (4340 [69.5%]). There were 1011 (16.2%) Black participants, 735 (11.8%) Hispanic/Latinx participants, and 3929 (62.9%) White participants. Patients in lower nSES areas had higher rates of nonadherence, ranging from 51.7% in the lowest quartile (731 of 1086 participants) to 40.0% in the highest quartile (563 of 1086 participants) ( P &amp;amp;lt; .001). In adjusted analysis, patients living in the lower 2 nSES quartiles had significantly higher odds of nonadherence when compared with patients living in the highest nSES quartile (quartile 1: odds ratio [OR], 1.57 [95% CI, 1.35-1.83]; quartile 2: OR, 1.35 [95% CI, 1.16-1.56]). No mediation by access to transportation and pharmacy density was found, but a small amount of mediation by neighborhood walkability was observed. Conclusions and Relevance In this retrospective cohort study of patients with HFrEF, living in a lower nSES area was associated with higher rates of GDMT nonadherence. These findings highlight the importance of considering neighborhood-level disparities when developing approaches to improve medication adherence.
Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer
Authors: Krishnansu S. Tewari, Nicoletta Colombo, Bradley J. Monk, Coraline Dubot, M. Valeria Cáceres, Kosei Hasegawa, Ronnie Shapira-Frommer, Pamela Salman, Eduardo Yañez, Mahmut Gümüş, Mivael Olivera Hurtado de Mendoza, Vanessa Samouëlian, Vincent Castonguay, Alexander Arkhipov, Cumhur Tekin, Kan Li, Sarper Toker, Stephen M. Keefe, Domenica Lorusso
Journal: JAMA Oncology (2023)

The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.
Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: Promises, problems and prospects
Authors: Chui‐Yan Ma, Yuqing Zhai, Chung Tony Li, Jie Liu, Xiang Xu, Hao Chen, Hung‐Fat Tse, Qizhou Lian
Journal: Medicinal Research Reviews (2023)

Abstract Mesenchymal stem cells (MSCs) are one of the few stem cell types used in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair, due to their unique paracrine capacity, multiple differentiation potential, active components in exosomes, and effective mitochondria donation. At present, MSCs derived from tissues such as bone marrow and umbilical cord are widely applied in preclinical and clinical studies. Nevertheless, there remain challenges to the maintenance of consistently good quality MSCs derived from different donors or tissues, directly impacting their application as advanced therapy products. In this review, we discuss the promises, problems, and prospects associated with translation of MSC research into a pharmaceutical product. We review the hurdles encountered in translation of MSCs and MSC–exosomes from the research bench to an advanced therapy product compliant with good manufacturing practice (GMP). These difficulties include how to set up GMP‐compliant protocols, what factors affect raw material selection, cell expansion to product formulation, establishment of quality control (QC) parameters, and quality assurance to comply with GMP standards. To avoid human error and reduce the risk of contamination, an automatic, closed system that allows real‐time monitoring of QC should be considered. We also highlight potential advantages of pluripotent stem cells as an alternative source for MSC and exosomes generation and manufacture.
Prevalence of Short Peer Reviews in 3 Leading General Medical Journals
Authors: Pascal Geldsetzer, Markus Heemann, Pauli Tikka, Grace Wang, Marika Mae Cusick, Ali Lenjani, Nandita Krishnan
Journal: JAMA Network Open (2023)

High-quality peer reviews are often thought to be essential to ensuring the integrity of the scientific publication process, but measuring peer review quality is challenging. Although imperfect, review word count could potentially serve as a simple, objective metric of review quality.
Searching Beyond Programmed Cell Death Ligand 1 in Metastatic Breast Cancer—Still Haven’t Found What We’re Looking For
Authors: Dionisia Quiroga, Margaret E. Gatti-Mays
Journal: JAMA Oncology (2023)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Oncology journal
Unwinding of Medicaid Continuous Enrollment Exposes Millions to Disrupted Care—“Be Kind, Rewind”
Authors: Justin M. Barnes, K. Robin Yabroff, Fumiko Chino
Journal: JAMA Oncology (2023)

This Viewpoint discusses the causes and consequences of Medicaid unwinding and disenrollment and proposes solutions to minimize disenrollment and improve coverage uptake and health care access.
Diversity in Mission Statements and Among Students at US Medical Schools Accredited Since 2000
Authors: Kelsey West, Leen Oyoun Alsoud, Kathryn Andolsek, Sara Sorrell, Cynthia Al Hageh, Halah Ibrahim
Journal: JAMA Network Open (2023)

Importance Diversity in the physician workforce improves patient care and decreases health disparities. Recent calls for social justice have highlighted the importance of medical school commitment to diversity and social justice, and newly established medical schools are uniquely positioned to actively fulfill the social mission of medicine. Objective To identify diversity language in the mission statements of all medical schools accredited since 2000 and to determine whether the presence of diversity language was associated with increased diversity in the student body. Design, Setting, and Participants Cross-sectional study of public websites conducted between January 6, 2023, and March 31, 2023. Qualitative content analysis of mission statements was conducted using a deductive approach. Eligible schools were identified from the 2021-2022 Medical School Admission Requirements and American Medical Colleges and American Association of Colleges of Osteopathic Medicine websites. Each school’s publicly available website was also reviewed for its mission and student body demographics. All United States allopathic and osteopathic medical schools that have been accredited and have enrolled students since 2000. Exposure Content analysis of medical school mission statements. Main Outcomes and Measures Prevalence of diversity language in medical school mission statements and its association with student body racial diversity. Data were analyzed in 5-year groupings: 2001 to 2005, 2006 to 2010, 2011 to 2015, and 2016 to 2020). Results Among the 60 new medical schools (33 [55%] allopathic and 27 [45%] osteopathic; 6927 total students), 33 (55%) incorporated diversity language into their mission statements. In 2022, American Indian or Alaska Native individuals accounted for 0.26% of students (n = 18), Black or African American students constituted 5% (n = 368), and Hispanic or Latinx individuals made up 12% (n = 840). The percentage of schools with diversity language in their mission statements did not change significantly in schools accredited across time frames (60% in 2001: mean [SE], 0.60 [0.24] vs 50% in 2020: mean [SE], 0.50 [0.11]). The percentage of White students decreased significantly over the time period (26% vs 15% students in 2001-2005 and 2016-2020, respectively; P &amp;amp;lt; .001). No significant differences were observed in student body racial or ethnic composition between schools with mission statements that included diversity language and those without. Conclusions and Relevance In this cross-sectional study of US medical schools accredited since 2000, diversity language was present in approximately half of the schools’ mission statements and was not associated with student body diversity. Future studies are needed to identify the barriers to increasing diversity in all medical schools.
Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2
Authors: Sara Pusceddu, Francesca Corti, Natalie Prinzi, Federico Nichetti, Silva Ljevar, Adele Busico, Tommaso Cascella, Rita Leporati, Simone Oldani, Chiara Carlotta Pircher, Jorgelina Coppa, Veronica Resi, Massimo Milione, Marco Maccauro, Rosalba Miceli, Elena Tamborini, Federica Perrone, Carlo Spreafico, Monica Niger, Federica Morano, Filippo Pietrantonio, Ettore Seregni, Luigi Mariani, Vincenzo Mazzaferro, Giorgia Di Liberti, Giovanni Fucà, Filippo de Braud, Claudio Vernieri
Journal: Journal of Hematology & Oncology (2023)

Abstract In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.
Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer
Authors: Brian D. Lehmann, Vandana G. Abramson, E. Claire Dees, Payal D. Shah, Tarah J. Ballinger, Claudine Isaacs, Cesar A. Santa-Maria, Hanbing An, Paula I. Gonzalez-Ericsson, Melinda E. Sanders, Kimberly C. Newsom, Richard G. Abramson, Quanhu Sheng, Chih-Yuan Hsu, Yu Shyr, Antonio C. Wolff, Jennifer A. Pietenpol
Journal: JAMA Oncology (2023)

Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.
Alcohol Intake Thresholds Among Individuals With Steatotic Liver Disease
Authors: Yee Hui Yeo, Yixuan Zhu, Juan Pablo Arab, Wenjing Ni, Xiaoming Xu, Junping Shi, Jie Li
Journal: JAMA Network Open (2023)

This cohort study aims to elucidate the dose-dependent association of alcohol use with progression of steatotic liver disease using a noninvasive, low-cost method.
Sleep Disturbances and Emotional and Behavioral Difficulties Among Preschool-Aged Children
Authors: Yujiao Deng, Zichen Zhang, Yiding Gui, Wen Li, Tingyu Rong, Yanrui Jiang, Qi Zhu, Jin Zhao, Yunting Zhang, Guanghai Wang, Fan Jiang
Journal: JAMA Network Open (2023)

Importance Sleep disturbances and mental health problems are highly comorbid and bidirectionally correlated across childhood. The association between the natural history of sleep disturbances and the transition of mental health problems has not been quantified. Objective To examine the association between the natural history of sleep disturbances and resolved and incident emotional and behavioral difficulties (EBDs). Design, Setting, and Participants This cohort study used data from the Shanghai Children’s Health, Education and Lifestyle Evaluation–Preschool (SCHEDULE-P), a prospective and population-based longitudinal cohort study of children enrolled in preschools in Shanghai, China, from November 10 to 24, 2016. A total of 20 324 children aged 3 to 4 years were recruited from the junior class of 191 kindergartens, of whom 17 233 (84.8%) participated in the 2-year follow-up. A multilevel regression model was used to evaluate the association between the development of sleep disturbances and the occurrence of resolved and incident EBDs. The data analysis spanned from August 4, 2021, to October 31, 2023. Exposures Sleep disturbances were assessed using the Children’s Sleep Habit Questionnaire; EBDs were assessed using the Strengths and Difficulties Questionnaire. Main Outcomes and Measures Occurrence of incident and resolved EBDs at the 2-year follow-up. Results The cohort included 17 182 participants, with a mean (SD) age of 3.73 (0.29) years at enrollment; 52.0% were boys. The prevalence of EBDs at school entry and graduation years was 27.8% and 18.7%, respectively, while the prevalence of sleep disturbances was 41.3% and 31.5%, respectively. Among those with EBDs at the entry year, 35.0% maintained stability in the graduation year, while sleep disturbances were stable in 50.0% of those with sleep disturbances. After controlling for confounding factors, the odds ratio (OR) for resolved EBDs was lower in the incident sleep disturbance (ISD) group (OR, 0.50 [95% CI, 0.41-0.62]; P &amp;amp;lt; .001) and stable sleep disturbance (SSD) group (OR, 0.47 [95% CI, 0.40-0.56]; P &amp;amp;lt; .001) compared with the group with no sleep disturbances. The ORs for incident EBDs among the ISD group (OR, 2.58 [95% CI, 2.22-3.01]; P &amp;amp;lt; .001) and SSD group (OR, 2.29, [95% CI, 1.98-2.64]; P &amp;amp;lt; .001) were higher than among the group with no sleep disturbances. Conclusions and Relevance In this prospective cohort study, the natural history of sleep disturbances among preschool-aged children was associated with both resolved and incident EBDs. Routine screening and precise intervention for sleep disturbances may benefit the psychosocial well-being of this population.
Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Locally Advanced and Metastatic Renal Cell Carcinoma
Authors: Alireza Ghoreifi, Ulka Vaishampayan, Ming Yin, Sarah P. Psutka, Hooman Djaladat
Journal: JAMA Oncology (2023)

The therapeutic landscape of advanced renal cell carcinoma (RCC) has rapidly evolved in the past 2 decades, with the advent of cytokines therapy followed by targeted therapies and novel immune checkpoint inhibitors (ICI). This article aims to review the current evidence and ongoing trials of neoadjuvant or prenephrectomy ICI therapy in patients with locally advanced and metastatic RCC.