tbuckley/cabot-search huggingface dataset:
The Conundrum of Lung Disease and Drug Hypersensitivity‐like Reactions in Systemic Juvenile Idiopathic Arthritis
Authors: Bryce A. Binstadt, Peter A. Nigrovic
Journal: Arthritis & Rheumatology (2022)

An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung disease (SJIA-LD) have a history of clinical and laboratory features resembling drug reaction with eosinophilia and systemic symptoms (DRESS), a presentation now convincingly associated with HLA-DRB1*15. Treatment of DRESS typically requires drug discontinuation, a daunting prospect for clinicians and families who rely upon these agents. Here we review SJIA-LD and its associated DRESS-like phenotype. We suggest an alternative explanation, the cytokine plasticity hypothesis, proposing that IL-1 and IL-6 blockers modulate the milieu in which T cells develop, leading to a pathologic immune response triggered through exposure to common microbes, or to other exogenous or endogenous antigens, rather than to the drugs themselves. This hypothesis differs from DRESS in mechanism but also in clinical implications, predicting that control of pathogenic T cells could permit continued use of IL-1 and IL-6 antagonists in some individuals. The spectrum posed by these two hypotheses provides a conceptual framework that will guide investigation into the pathogenesis of SJIA-LD and may open up new therapeutic avenues for patients with systemic JIA.
Drug-induced mast cell eradication: A novel approach to treat mast cell activation disorders?
Authors: Peter Valent, Cem Akin, Karin Hartmann, Andreas Reiter, Jason Gotlib, Karl Sotlar, Wolfgang R. Sperr, Lina Degenfeld-Schonburg, Dubravka Smiljkovic, Massimo Triggiani, Hans-Peter Horny, Michel Arock, Stephen J. Galli, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2022)

Mast cell (MC) activation is a key event in allergic reactions, other inflammatory states, and MC activation syndromes. MC-stabilizing agents, mediator-targeting drugs, and drugs interfering with mediator effects are often prescribed for these patients. However, the clinical efficacy of these drugs varies depending on the numbers of involved MCs and the underlying pathology. One straightforward approach would be to eradicate the primary target cell. To date however, no MC-eradicating treatment approach has been developed for patients with MC activation disorders. Nevertheless, recent data suggest that long-term treatment with agents effectively inhibiting KIT function results in the virtual eradication of tissue MCs and a sustained decrease in serum tryptase levels. In many of these patients, MC depletion is associated with a substantial improvement in mediator-induced symptoms. In patients with an underlying KIT D816V-positive mastocytosis, such MC eradication requires an effective inhibitor of KIT D816V, such as avapritinib. However, the use of KIT inhibitors must be balanced against their potential side effects. Here we discuss MC-eradicating strategies in various disease models, the feasibility of this approach, available clinical data, and future prospects for the use of KIT-targeting drugs in MC activation disorders.
TCTAP A-033 Percutaneous Coronary Intervention of Saphenous Vein Graft in Post-CABG Patient - Outcome Experiences at Our Center - SVG to OM are More Likely to Develop Occlusion
Authors: Ahm Waliul Islam, Shams Munwar, A.Q.M. Reza, Shahab Uddin Talukder, Tamzeed Ahmed, Kazi Atiqur Rahman
Journal: Journal of the American College of Cardiology (2022)
TCTAP A-048 Reduction of Clinical Events in High-Risk Hypertension Patients Treated With Renal Denervation: A Modeled Estimate From 36-Month Global SYMPLICTY Registry Data
Authors: Markus Schlaich, Jan Benjamin Pietzsch, Felix Mahfoud, Bryan Wiliams, Giuseppe Mancia, Krzystzof Narkiewicz, Luis Ruilope, Doug Hettrick, Michael Böhm, Roland E. Schmieder
Journal: Journal of the American College of Cardiology (2022)
Retinal receptive-field substructure: scaffolding for coding and computation
Authors: Sören J. Zapp, Steffen Nitsche, Tim Gollisch
Journal: Trends in Neurosciences (2022)

The center-surround receptive field of retinal ganglion cells represents a fundamental concept for how the retina processes and encodes visual information. Yet, traditional approaches of using the receptive field as a linear filter to integrate light intensity over space often do not capture the responses of a ganglion cell to complex visual stimuli. Thus, models with local nonlinearities in subunits of the receptive field or with local temporal dynamics are emerging to better reflect relevant aspects of retinal circuitry and capture stimulus encoding. Here, we review recent efforts to identify such receptive-field substructure and evaluate its role in visual stimulus encoding. The concomitant development of new computational tools may pave the way toward a model-based, functional approach to retinal circuit analysis.
Association Between Physical Activity and Risk of Depression
Authors: Matthew Pearce, Leandro Garcia, Ali Abbas, Tessa Strain, Felipe Barreto Schuch, Rajna Golubic, Paul Kelly, Saad Khan, Mrudula Utukuri, Yvonne Laird, Alexander Mok, Andrea Smith, Marko Tainio, Søren Brage, James Woodcock
Journal: JAMA Psychiatry (2022)

Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain.
Venom Gene Sequence Diversity and Expression Jointly Shape Diet Adaptation in Pitvipers
Authors: Andrew J. Mason, Matthew L. Holding, Rhett M. Rautsaw, Darin R. Rokyta, Christopher L. Parkinson, H. Lisle Gibbs
Journal: Molecular Biology and Evolution (2022)

Abstract Understanding the joint roles of protein sequence variation and differential expression during adaptive evolution is a fundamental, yet largely unrealized goal of evolutionary biology. Here, we use phylogenetic path analysis to analyze a comprehensive venom-gland transcriptome dataset spanning three genera of pitvipers to identify the functional genetic basis of a key adaptation (venom complexity) linked to diet breadth (DB). The analysis of gene-family-specific patterns reveals that, for genes encoding two of the most important venom proteins (snake venom metalloproteases and snake venom serine proteases), there are direct, positive relationships between sequence diversity (SD), expression diversity (ED), and increased DB. Further analysis of gene-family diversification for these proteins showed no constraint on how individual lineages achieved toxin gene SD in terms of the patterns of paralog diversification. In contrast, another major venom protein family (PLA2s) showed no relationship between venom molecular diversity and DB. Additional analyses suggest that other molecular mechanisms—such as higher absolute levels of expression—are responsible for diet adaptation involving these venom proteins. Broadly, our findings argue that functional diversity generated through sequence and expression variations jointly determine adaptation in the key components of pitviper venoms, which mediate complex molecular interactions between the snakes and their prey.
Myocarditis Adverse Event Less Common After COVID-19 Vaccine Booster
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

The risk of adolescents developing myocarditis is lower after a booster dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine than after the second dose, according to a CDC analysis of data from the Vaccine Adverse Event Reporting System (VAERS).
Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study
Authors: Scott A Nabity, Kelvin Mponda, Steve Gutreuter, Diya Surie, Suzgo B Zimba, Laphiod Chisuwo, Allison Moffitt, Anne M Williams, Andrea J Sharma, Rebekah E Marshall, Mabvuto J Chiwaula, Robin da Silva, Tapiwa Kumwenda, Lloyd Chilikutali, Shallom Mwamale, Esther Nagoli, Gerald Mwenyeheri, Dingase Ngongonda, Esther Kaunda, Fredrick Mtoto, Vorster Mhango, Khumbo Mbewe, Michael Melgar, Michael Odo, Andreas Jahn, Nicole Buono, Alice Maida, Belaineh Girma, Thokozani Kalua, Rose Nyirenda, Joram Sunguti, Godfrey Woelk, Laurence J Gunde, Tigest F Mekonnen, Thulani Maphosa, Evelyn J Kim, Andrew F Auld, Adamson S Muula, John E Oeltmann
Journal: The Lancet Global Health (2022)

Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population.
Schizophrenia Imaging Signatures and Their Associations With Cognition, Psychopathology, and Genetics in the General Population
Authors: Ganesh B. Chand, Pankhuri Singhal, Dominic B. Dwyer, Junhao Wen, Guray Erus, Jimit Doshi, Dhivya Srinivasan, Elizabeth Mamourian, Erdem Varol, Aristeidis Sotiras, Gyujoon Hwang, Paola Dazzan, Rene S. Kahn, Hugo G. Schnack, Marcus V. Zanetti, Eva Meisenzahl, Geraldo F. Busatto, Benedicto Crespo-Facorro, Christos Pantelis, Stephen J. Wood, Chuanjun Zhuo, Russell T. Shinohara, Haochang Shou, Yong Fan, Nikolaos Koutsouleris, Antonia N. Kaczkurkin, Tyler M. Moore, Anurag Verma, Monica E. Calkins, Raquel E. Gur, Ruben C. Gur, Marylyn D. Ritchie, Theodore D. Satterthwaite, Daniel H. Wolf, Christos Davatzikos
Journal: American Journal of Psychiatry (2022)

Objective: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia—signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume—could be replicated in an independent schizophrenia sample, and investigated whether expression of these signatures can be detected at the population level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. Methods: This cross-sectional study used an independent schizophrenia-control sample (N=347; ages 16–57 years) for replication of imaging signatures, and then examined two independent population-level data sets: typically developing youths and youths with psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort (N=359; ages 16–23 years) and adults in the UK Biobank study (N=836; ages 44–50 years). The authors quantified signature expression using support-vector machine learning and compared cognition, psychopathology, and polygenic risk between signatures. Results: Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youths with psychosis spectrum symptoms than in typically developing youths, whereas signature 2 frequency was similar in the two groups. In both youths and adults, signature 1 was associated with worse cognitive performance than signature 2. Compared with adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. Conclusions: The authors successfully replicated two neuroanatomical signatures of schizophrenia and describe their prevalence in population-based samples of youths and adults. They further demonstrated distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.
TCTAP A-022 Long-Term Outcome of Transcatheter Aortic Valve Replacement Versus Surgical Aortic Valve Replacement for Aortic Stenosis: A Meta-Analysis
Authors: Hendy Bhaskara Perdana Putra, Richardus Rukma Juslim, Benny Jovie, Yusra Pintaningrum, Sekar Rahadisiwi
Journal: Journal of the American College of Cardiology (2022)
The interferon-stimulated gene RIPK1 regulates cancer cell intrinsic and extrinsic resistance to immune checkpoint blockade
Authors: Lisa Cucolo, Qingzhou Chen, Jingya Qiu, Yongjun Yu, Max Klapholz, Krista A Budinich, Zhaojun Zhang, Yue Shao, Igor E Brodsky, Martha S Jordan, D Gary Gilliland, Nancy R Zhang, Junwei Shi, Andy J Minn
Journal: Immunity (2022)
Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study
Authors: Helene Kildegaard, Lars Christian Lund, Mikkel Højlund, Lone Graff Stensballe, Anton Pottegård
Journal: BMJ (2022)

Abstract Objectives To assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents. Design Cohort study. Setting Nationwide Danish healthcare registers. Participants All Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021. Main outcome measures Risk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose. Results Of 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents received BNT162b2. Compared with unvaccinated adolescents, the estimated vaccine effectiveness among 229 799 adolescents vaccinated with one dose was 62% (95% confidence interval 59% to 65%) after 20 days, and among 175 176 vaccinated with two doses was 93% (92% to 94%) after 60 days during a period when delta was the dominant variant. Conclusions The absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children and adolescents, although MIS-C occurred in 0.05% (32/70 666) of participants with RT-PCR confirmed SARS-CoV-2 infection. In adjusted analyses, rates of general practitioner visits were slightly increased in SARS-CoV-2 positive children and adolescents, which could indicate persisting symptoms. BNT162b2 appeared to be effective in reducing the risk of SARS-CoV-2 infection with the delta variant in adolescents.
A high-generalizability machine learning framework for predicting the progression of Alzheimer’s disease using limited data
Authors: Caihua Wang, Yuanzhong Li, Yukihiro Tsuboshita, Takuya Sakurai, Tsubasa Goto, Hiroyuki Yamaguchi, Yuichi Yamashita, Atsushi Sekiguchi, Hisateru Tachimori, Caihua Wang, Yuanzhong Li, Tsubasa Goto
Journal: npj Digital Medicine (2022)

Abstract Alzheimer’s disease is a neurodegenerative disease that imposes a substantial financial burden on society. A number of machine learning studies have been conducted to predict the speed of its progression, which varies widely among different individuals, for recruiting fast progressors in future clinical trials. However, because the data in this field are very limited, two problems have yet to be solved: the first is that models built on limited data tend to induce overfitting and have low generalizability, and the second is that no cross-cohort evaluations have been done. Here, to suppress the overfitting caused by limited data, we propose a hybrid machine learning framework consisting of multiple convolutional neural networks that automatically extract image features from the point of view of brain segments, which are relevant to cognitive decline according to clinical findings, and a linear support vector classifier that uses extracted image features together with non-image information to make robust final predictions. The experimental results indicate that our model achieves superior performance (accuracy: 0.88, area under the curve [AUC]: 0.95) compared with other state-of-the-art methods. Moreover, our framework demonstrates high generalizability as a result of evaluations using a completely different cohort dataset (accuracy: 0.84, AUC: 0.91) collected from a different population than that used for training.
Multifaceted intervention to reduce haemodialysis catheter related bloodstream infections: REDUCCTION stepped wedge, cluster randomised trial
Authors: Sradha Kotwal, Alan Cass, Sarah Coggan, Nicholas A Gray, Stephen Jan, Stephen McDonald, Kevan R Polkinghorne, Kris Rogers, Girish Talaulikar, Gian Luca Di Tanna, Martin Gallagher
Journal: BMJ (2022)

Abstract Objective To identify whether multifaceted interventions, or care bundles, reduce catheter related bloodstream infections (CRBSIs) from central venous catheters used for haemodialysis. Design Stepped wedge, cluster randomised design. Setting 37 renal services across Australia. Participants All adults (age ≥18 years) under the care of a renal service who required insertion of a new haemodialysis catheter. Interventions After a baseline observational phase, a service-wide, multifaceted intervention bundle that included elements of catheter care (insertion, maintenance, and removal) was implemented at one of three randomly assigned time points (12 at the first time point, 12 at the second, and 13 at the third) between 20 December 2016 and 31 March 2020. Main outcomes measure The primary endpoint was the rate of CRBSI in the baseline phase compared with intervention phase at the renal service level using the intention-to-treat principle. Results 1.14 million haemodialysis catheter days of use were monitored across 6364 patients. Patient characteristics were similar across baseline and intervention phases. 315 CRBSIs occurred (158 in the baseline phase and 157 in the intervention phase), with a rate of 0.21 per 1000 days of catheter use in the baseline phase and 0.29 per 1000 days in the intervention phase, giving an incidence rate ratio of 1.37 (95% confidence interval 0.85 to 2.21; P=0.20). This translates to one in 10 patients who undergo dialysis for a year with a catheter experiencing an episode of CRBSI. Conclusions Among patients who require a haemodialysis catheter, the implementation of a multifaceted intervention did not reduce the rate of CRBSI. Multifaceted interventions to prevent CRBSI might not be effective in clinical practice settings. Trial registration Australia New Zealand Clinical Trials Registry ACTRN12616000830493.
Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
Authors: Karim Fizazi, Stéphanie Foulon, Joan Carles, Guilhem Roubaud, Ray McDermott, Aude Fléchon, Bertrand Tombal, Stéphane Supiot, Dominik Berthold, Philippe Ronchin, Gabriel Kacso, Gwenaëlle Gravis, Fabio Calabro, Jean-François Berdah, Ali Hasbini, Marlon Silva, Antoine Thiery-Vuillemin, Igor Latorzeff, Loïc Mourey, Brigitte Laguerre, Sophie Abadie-Lacourtoisie, Etienne Martin, Claude El Kouri, Anne Escande, Alvar Rosello, Nicolas Magne, Friederike Schlurmann, Frank Priou, Marie-Eve Chand-Fouche, Salvador Villà Freixa, Muhammad Jamaluddin, Isabelle Rieger, Alberto Bossi
Journal: The Lancet (2022)
Drug Pricing With Evidence Development
Authors: James C. Robinson
Journal: JAMA (2022)

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Estimating global, regional, and national daily and cumulative infections with SARS-CoV-2 through Nov 14, 2021: a statistical analysis
Authors: Ryan M Barber, Reed J D Sorensen, David M Pigott, Catherine Bisignano, Austin Carter, Joanne O Amlag, James K Collins, Cristiana Abbafati, Christopher Adolph, Adrien Allorant, Aleksandr Y Aravkin, Bree L Bang-Jensen, Emma Castro, Suman Chakrabarti, Rebecca M Cogen, Emily Combs, Haley Comfort, Kimberly Cooperrider, Xiaochen Dai, Farah Daoud, Amanda Deen, Lucas Earl, Megan Erickson, Samuel B Ewald, Alize J Ferrari, Abraham D Flaxman, Joseph Jon Frostad, Nancy Fullman, John R Giles, Gaorui Guo, Jiawei He, Monika Helak, Erin N Hulland, Bethany M Huntley, Alice Lazzar-Atwood, Kate E LeGrand, Stephen S Lim, Akiaja Lindstrom, Emily Linebarger, Rafael Lozano, Beatrice Magistro, Deborah Carvalho Malta, Johan Månsson, Ana M Mantilla Herrera, Ali H Mokdad, Lorenzo Monasta, Mohsen Naghavi, Shuhei Nomura, Christopher M Odell, Latera Tesfaye Olana, Samuel M Ostroff, Maja Pasovic, Spencer A Pease, Robert C Reiner Jr, Grace Reinke, Antonio Luiz P Ribeiro, Damian F Santomauro, Aleksei Sholokhov, Emma E Spurlock, Ruri Syailendrawati, Roman Topor-Madry, Anh Truc Vo, Theo Vos, Rebecca Walcott, Ally Walker, Kirsten E Wiens, Charles Shey Wiysonge, Nahom Alemseged Worku, Peng Zheng, Simon I Hay, Emmanuela Gakidou, Christopher J L Murray
Journal: The Lancet (2022)

Timely, accurate, and comprehensive estimates of SARS-CoV-2 daily infection rates, cumulative infections, the proportion of the population that has been infected at least once, and the effective reproductive number (R