tbuckley/cabot-search huggingface dataset:
Liver X receptors are required for thymic resilience and T cell output
Authors: Christopher T. Chan, Ashley M. Fenn, Nina K. Harder, John E. Mindur, Cameron S. McAlpine, Jyoti Patel, Colin Valet, Sara Rattik, Yoshiko Iwamoto, Shun He, Atsushi Anzai, Florian Kahles, Wolfram C. Poller, Henrike Janssen, Lai Ping Wong, Carlos Fernandez-Hernando, David R. Koolbergen, Anja M. van der Laan, Laurent Yvan-Charvet, Ruslan I. Sadreyev, Matthias Nahrendorf, Marit Westerterp, Alan R. Tall, Jan-Ake Gustafsson, Filip K. Swirski
Journal: The Journal of Experimental Medicine (2020)

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)—a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity—critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire. LXRαβ’s functions are cell specific, and the resulting phenotypes are mutually independent. Although thymic macrophages require LXRαβ for cholesterol efflux, thymic epithelial cells (TECs) use LXRαβ for self-renewal and thymocytes for negative selection. Consequently, TEC-derived LXRαβ protects against homeostatic premature involution and orchestrates thymic regeneration following stress, while thymocyte-derived LXRαβ limits cell disposal during negative selection and confers heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXRαβ governs T lymphocyte education and illuminate LXRαβ’s indispensable roles in adaptive immunity.
Re-establishing the Role of Robot-assisted Radical Cystectomy After the 2020 EAU Muscle-invasive and Metastatic Bladder Cancer Guideline Panel Recommendations
Authors: Francesco Montorsi, Marco Bandini, Alberto Briganti, Prokar Dasgupta, Andrea Gallina, Michele Gallucci, Inderbir S. Gill, Khurshid A. Guru, Ashok Hemal, Mani Menon, Marco Moschini, Declan G. Murphy, Dipen J. Parekh, Hiten D. Patel, Hiten R.H. Patel, Michael Stöckle, Ash K. Tewari, Carl J. Wijburg, Peter Wiklund, Timothy G. Wilson, Alexandre Mottrie
Journal: European Urology (2020)
RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins
Authors: Jing Zhang, Jason Liu, Donghoon Lee, Jo-Jo Feng, Lucas Lochovsky, Shaoke Lou, Michael Rutenberg-Schoenberg, Mark Gerstein
Journal: Genome biology (2020)

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then, it further incorporates tissue-specific inputs to highlight disease-specific variants. Our results demonstrate RADAR can successfully pinpoint variants, both somatic and germline, associated with RBP-function dysregulation, which cannot be found by most current prioritization methods, for example, variants affecting splicing.
Wellness Program Failed to Improve Employee Health
Authors: Anita Slomski
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
Evaluation of reproducible and transparent research practices in pulmonology
Authors: C.A. Smith, J. Nolan, D.J. Tritz, T.E. Heavener, J. Pelton, K. Cook, M. Vassar
Journal: Pulmonology (2020)

Study reproducibility is valuable for validating or refuting results. Provision of reproducibility indicators, such as materials, protocols, and raw data in a study improve its potential for reproduction. Efforts to reproduce noteworthy studies in the biomedical sciences have resulted in an overwhelming majority of them being found to be unreplicable, causing concern for the integrity of research in other fields, including medical specialties. Here, we analyzed the reproducibility of studies in the field of pulmonology. 500 pulmonology articles were randomly selected from an initial PubMed search for data extraction. Two authors scoured these articles for reproducibility indicators including materials, protocols, raw data, analysis scripts, inclusion in systematic reviews, and citations by replication studies as well as other factors of research transparency including open accessibility, funding source and competing interest disclosures, and study preregistration. Few publications included statements regarding materials (10%), protocols (1%), data (15%), and analysis script (0%) availability. Less than 10% indicated preregistration. More than half of the publications analyzed failed to provide a funding statement. Conversely, 63% of the publications were open access and 73% included a conflict of interest statement. Overall, our study indicates pulmonology research is currently lacking in efforts to increase replicability. Future studies should focus on providing sufficient information regarding materials, protocols, raw data, and analysis scripts, among other indicators, for the sake of clinical decisions that depend on replicable or refutable results from the primary literature.
Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis
Authors: Antonios Douros, Lisa M. Lix, Michael Fralick, Sophie Dell'Aniello, Baiju R. Shah, Paul E. Ronksley, Éric Tremblay, Nianping Hu, Silvia Alessi-Severini, Anat Fisher, Shawn C. Bugden, Pierre Ernst, Kristian B. Filion
Journal: Annals of Internal Medicine (2020)

Background: Sodium–glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA). Objective: To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes. Design: Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221) Setting: Electronic health care databases from 7 Canadian provinces and the United Kingdom. Patients: 208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors. Measurements: Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin. Results: Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk. Limitations: There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites. Conclusion: SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect. Primary Funding Source: Canadian Institutes of Health Research.
AB0425 PRELIMINARY EVALUATION OF THE SURAL NERVE USING 24-MHZ ULTRASOUND: A NEW APPROACH TO EVALUATE SURAL NEUROPATHY OF SJOGREN’S SYNDROME PATIENTS
Authors: F. Liu, J. Zhu, S. Zhang, D. LI, F. Liu, W. LI, Y. Liu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Peripheral neuropathy is one of the most frequent extraglandular manifestations of primary Sjögren’s syndrome (pSS). The diagnosis of peripheral neuropathy complications of pSS is based primarily on careful neurologic examination and electrodiagnostic tests. The value of ultrasound in peripheral nerve has been recognized. However, little clinical researches have focused specifically on cutaneous nerve of pSS. Objectives: To evaluate the morphological changes of sural nerve in patients with pSS by high-frequency ultrasound. Methods: The prospective study subjects consisted of 31 consecutive pSS patients underwent sural nerve biopsy and 30 healthy volunteers as controls. The ultrasonic presentations of the fascicle, perineurium, epineurium of sural nerve were observed, and the cross-sectional areas (CSA) of the sural nerves was measured. Results: Among the 21 sural nerves confirmed by pathology, all showed the thickening of the perineurium and epineurium (Figure 1-2), and abnormal blood flow signal in perineurium or epineurium in 14 cases (Figure 2). The mean CSAs were (1.41±0.44) mm2 for the control group, and (1.58±0.48) mm2 for the case group (P&gt;0.05). In addition, the abnormal blood flow signal in sural nerve correlated with disease activity. Conclusion: This study indicated that high-frequency ultrasound may be a valuable tool for evaluating cutaneous nerve neuropathy of Sjogren’s syndrome patients. References: [1]Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554-8. [2]Terrier B, Lacroix C, Guillevin L, Hatron PY, Dhote R, Maillot F, et al. Diagnostic and prognostic relevance of neuromuscular biopsy in primary Sjögren’s syndrome-related neuropathy. Arthritis Rheum.2007;57(8):1520-9. [3]McCoy SS, Baer AN. Neurological Complications of Sjögren’s Syndrome: Diagnosis and Management. Curr Treatm Opt Rheumatol. 2017;3(4):275-88. [4]Carvajal Alegria G, Guellec D, Devauchelle-Pensec V, Saraux A. Is there specific neurological disorders of primary Sjögren’s syndrome? Joint Bone Spine. 2015;82(2):86-9. Figure 1. Transverse sonograms of the sural nerve (arrows) V: indicates lesser saphenous vein Figure 2. Longitudinal sonograms of the sural nerve (arrows) The sonogram of sural nerve showed abnormal blood flow signal. V indicates lesser saphenous vein. Acknowledgments: This work was partly supported by National Natural Science Foundation of China (No. 81701712). Disclosure of Interests: : None declared
Dramatic Increase in US Congenital Syphilis Cases
Authors: Bridget M. Kuehn
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 enhanced prognostic score for overall survival of patients with cancer derived from a large real-world cohort
Authors: T. Becker, J. Weberpals, A.M. Jegg, W.V. So, A. Fischer, M. Weisser, F. Schmich, D. Rüttinger, A. Bauer-Mehren
Journal: Annals of Oncology (2020)

By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type.In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the 'Real wOrld PROgnostic score (ROPRO)'. We validated ROPRO in two independent phase I and III clinical studies.A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45-8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3-24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4-15.2) in Q2, 9.4 months (9.1-9.7) in Q3, and 4.7 months (4.6-4.8) in Q4. The ROPRO model performance indicators [C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819-0.825)] strongly outperformed those of the Royal Marsden Hospital Score [C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577-0.581)]. We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials.The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies.
Distinctive Demography, Biology, and Outcome of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Children With Down Syndrome: Children's Cancer Group Studies 2861 and 2891
Authors: Beverly J. Lange, Nathan Kobrinsky, Dorothy R. Barnard, Diane C. Arthur, Jonathan D. Buckley, William B. Howells, Stuart Gold, Jean Sanders, Steven Neudorf, Franklin O. Smith, William G. Woods
Journal: Blood (1998)
A novel method for precise detection of allergen‐specific IgE via immobilizing His‐tagged allergens to paper‐based device
Authors: Mengda Cao, Xisi Han, Chen Lu, Yujie Wang, Zhiqiang Xu, Shuangxi Wang, Bicong Zhou, Chengwu Zhang, Changmin Yu, Lin Li, Ji‐Fu Wei
Journal: Allergy (2020)

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The Differential Impact of Age on Vision-Related Quality of Life across the Visual Impairment Spectrum
Authors: Ryan Eyn Kidd Man, Alfred Tau Liang Gan, Eva K. Fenwick, Preeti Gupta, Sahil Thakur, Xiao Ling Fang, Ching-Yu Cheng, Tien Yin Wong, Ecosse L. Lamoureux
Journal: Ophthalmology (2020)
Ablation of the Brca1–Palb2 Interaction Phenocopies Fanconi Anemia in Mice
Authors: Dongju Park, Stephen M. Bergin, Dan Jones, Peng Ru, Christopher S. Koivisto, Young-Jun Jeon, Gina M. Sizemore, Raleigh D. Kladney, Ashley Hadjis, Reena Shakya, Thomas Ludwig
Journal: Cancer Research (2020)

Heterozygous mutations in the BRCA1 gene predispose women to breast and ovarian cancer, while biallelic BRCA1 mutations are a cause of Fanconi anemia (FA), a rare genetic disorder characterized by developmental abnormalities, early-onset bone marrow failure, increased risk of cancers, and hypersensitivity to DNA-crosslinking agents. BRCA1 is critical for homologous recombination of DNA double-strand breaks (DSB). Through its coiled-coil domain, BRCA1 interacts with an essential partner, PALB2, recruiting BRCA2 and RAD51 to sites of DNA damage. Missense mutations within the coiled-coil domain of BRCA1 (e.g., L1407P) that affect the interaction with PALB2 have been reported in familial breast cancer. We hypothesized that if PALB2 regulates or mediates BRCA1 tumor suppressor function, ablation of the BRCA1-PALB2 interaction may also elicit genomic instability and tumor susceptibility. We generated mice defective for the Brca1-Palb2 interaction (Brca1 L1363P in mice) and established MEF cells from these mice. Brca1L1363P/L1363P MEF exhibited hypersensitivity to DNA-damaging agents and failed to recruit Rad51 to DSB. Brca1L1363P/L1363P mice were viable but exhibited various FA symptoms including growth retardation, hyperpigmentation, skeletal abnormalities, and male/female infertility. Furthermore, all Brca1L1363P/L1363P mice exhibited macrocytosis and died due to bone marrow failure or lymphoblastic lymphoma/leukemia with activating Notch1 mutations. These phenotypes closely recapitulate clinical features observed in patients with FA. Collectively, this model effectively demonstrates the significance of the BRCA1-PALB2 interaction in genome integrity and provides an FA model to investigate hematopoietic stem cells for mechanisms underlying progressive failure of hematopoiesis and associated development of leukemia/lymphoma, and other FA phenotypes. SIGNIFICANCE: A new Brca1 mouse model for Fanconi anemia (FA) complementation group S provides a system in which to study phenotypes observed in human FA patients including bone marrow failure.See related commentary by Her and Bunting, p. 4044.
Health Care as an Ongoing Policy Project
Authors: Eric C. Schneider
Journal: New England Journal of Medicine (2020)

Interview with Dr. Eric Schneider on the policy challenges facing U.S. health care and opportunities for reform. (08:21)Download The United States lags behind peer countries on key health outcomes, and the pandemic has highlighted weaknesses of U.S. health care. Though Americans have long struggled to bring about a high-performing, affordable health care system, additional reforms are needed.
Gene-Drug Interactions in AML Patients Identified By RNA Sequencing and Comprehensive Ex Vivo Drug Sensitivity and Resistance Testing
Authors: Ashwini Kumar, Dishaben Rameshbhai Malani, Bhagwan Yadav, Matti Kankainen, Swapnil Potdar, Mika Kontro, Kimmo Porkka, Olli Kallioniemi, Simon Anders, Caroline A Heckman
Journal: Blood (2017)
Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN
Authors: Hélène F. E. Gleitz, Aurélien J. F. Dugourd, Nils B. Leimkühler, Inge A. M. Snoeren, Stijn N. R. Fuchs, Sylvia Menzel, Susanne Ziegler, Nicolaus Kröger, Ioanna Triviai, Guntram Büsche, Hans Kreipe, Bella Banjanin, Jessica E. Pritchard, Remco Hoogenboezem, Eric M. Bindels, Neele Schumacher, Stefan Rose-John, Shannon Elf, Julio Saez-Rodriguez, Rafael Kramann, Rebekka K. Schneider
Journal: Blood (2020)
Prevalence and incidence of intra‐ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from <scp>PARADIGM‐HF</scp> and <scp>ATMOSPHERE</scp>
Authors: Søren Lund Kristensen, Davide Castagno, Li Shen, Pardeep S. Jhund, Kieran F. Docherty, Rasmus Rørth, William T. Abraham, Akshay S. Desai, Kenneth Dickstein, Jean L. Rouleau, Michael R. Zile, Karl Swedberg, Milton Packer, Scott D. Solomon, Lars Køber, John J.V. McMurray
Journal: European Journal of Heart Failure (2020)

The importance of intra-ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials.The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device. At baseline, 1789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) right bundle branch block (RBBB), 454 (3.8%) non-specific IVCD, 2588 (21.8%) 'mildly abnormal' QRS (110-129 ms) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% confidence interval) LBBB 1.36 (1.23-1.50), RBBB 1.54 (1.31-1.79), non-specific IVCD 1.65 (1.40-1.94) and QRS 110-129 ms 1.35 (1.23-1.47), compared with QRS duration <110 ms. A total of 1234 (15.6%) patients developed new-onset QRS widening ≥130 ms (6.1 per 100 patient-years). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 patient-years) and was associated with a higher risk of the primary composite outcome [hazard ratio 1.42 (1.12-1.82)].In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat electrocardiogram review.ClinicalTrials.gov Identifier NCT0083658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).