tbuckley/cabot-search huggingface dataset:
Loss of KMT5C Promotes EGFR Inhibitor Resistance in NSCLC via LINC01510-Mediated Upregulation of MET
Authors: Arpita S. Pal, Alejandra Agredo, Nadia A. Lanman, Jihye Son, Ikjot Singh Sohal, Manvir Bains, Chennan Li, Jenna Clingerman, Kayla Gates, Andrea L. Kasinski
Journal: Cancer Research (2022)

EGFR inhibitors (EGFRi) are standard-of-care treatments administered to patients with non-small cell lung cancer (NSCLC) that harbor EGFR alterations. However, development of resistance posttreatment remains a major challenge. Multiple mechanisms can promote survival of EGFRi-treated NSCLC cells, including secondary mutations in EGFR and activation of bypass tracks that circumvent the requirement for EGFR signaling. Nevertheless, the mechanisms involved in bypass signaling activation are understudied and require further elucidation. In this study, we identify that loss of an epigenetic factor, lysine methyltransferase 5C (KMT5C), drives resistance of NSCLC to multiple EGFRis, including erlotinib, gefitinib, afatinib, and osimertinib. KMT5C catalyzed trimethylation of histone H4 lysine 20 (H4K20), a modification required for gene repression and maintenance of heterochromatin. Loss of KMT5C led to upregulation of an oncogenic long noncoding RNA, LINC01510, that promoted transcription of the oncogene MET, a component of a major bypass mechanism involved in EGFRi resistance. These findings underscore the loss of KMT5C as a critical event in driving EGFRi resistance by promoting a LINC01510/MET axis, providing mechanistic insights that could help improve NSCLC treatment.Dysregulation of the epigenetic modifier KMT5C can drive MET-mediated EGFRi resistance, implicating KMT5C loss as a putative biomarker of resistance and H4K20 methylation as a potential target in EGFRi-resistant lung cancer.
FilmArray Meningitis/Encephalitis (M/E) false-negative for cryptococcal meningitis
Authors: Pin-Han Wu, Chih-Hao Chen, Chia-Huei Chou, Mao-Wang Ho, Yu-Hsuan Liu, Hsiu-Hsien Lin, Kuan-Fei Chen, Po-Ren Hsueh
Journal: Journal of Infection (2022)
TCTAP A-056 Diagnostic Performance of Coronary In-Stent Restenosis by Coronary Computed Tomography Angiography
Authors: Dong-Gil Kim, Sung Woo Cho, Ji-Won Hwang, Sung Uk Kwon, Jae-Jin Kwak, Gung June Nam, Sung Yun Lee, Joon-Hyung Doh
Journal: Journal of the American College of Cardiology (2022)
TCTAP C-129 Endovascular Management of Complicated IgG4-Related Disease Periaortitis Refractory to Medical Therapy
Authors: Mohieldin Hezima, Yogesh Acharya, Joshua Ramjohn, David Miresse, Omer Omer, Hesham Elzomor, Osama Soliman, Sherif Sultan
Journal: Journal of the American College of Cardiology (2022)
Myeloid Cell PKM2 Deletion Enhances Efferocytosis and Reduces Atherosclerosis
Authors: Prakash Doddapattar, Rishabh Dev, Madankumar Ghatge, Rakesh B. Patel, Manish Jain, Nirav Dhanesha, Steven R. Lentz, Anil K. Chauhan
Journal: Circulation Research (2022)

The glycolytic enzyme PKM2 (pyruvate kinase muscle 2) is upregulated in monocytes/macrophages of patients with atherosclerotic coronary artery disease. However, the role of cell type-specific PKM2 in the setting of atherosclerosis remains to be defined. We determined whether myeloid cell-specific PKM2 regulates efferocytosis and atherosclerosis.
Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the <scp>AC‐TIVE</scp> study, an <scp>Italian nationwide survey</scp>
Authors: Marco Merlo, Linda Pagura, Aldostefano Porcari, Matteo Cameli, Giuseppe Vergaro, Beatrice Musumeci, Elena Biagini, Marco Canepa, Lia Crotti, Massimo Imazio, Cinzia Forleo, Francesco Cappelli, Federico Perfetto, Stefano Favale, Gianluca Di Bella, Franca Dore, Francesca Girardi, Daniela Tomasoni, Rita Pavasini, Valeria Rella, Giuseppe Palmiero, Martina Caiazza, Maria Cristina Carella, Andrea Igoren Guaricci, Giovanna Branzi, Angelo Giuseppe Caponetti, Giulia Saturi, Giovanni La Malfa, Andrea Carlo Merlo, Alessandro Andreis, Francesco Bruno, Francesca Longo, Maddalena Rossi, Guerino Giuseppe Varrà, Riccardo Saro, Luca Di Ienno, Giuseppe De Carli, Elisa Giacomin, Chiara Arzilli, Giuseppe Limongelli, Camillo Autore, Iacopo Olivotto, Luigi Badano, Gianfranco Parati, Stefano Perlini, Marco Metra, Michele Emdin, Claudio Rapezzi, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2022)
Association of Birth Defects With Child Mortality Before Age 14 Years
Authors: Marie-Laure Sattolo, Laura Arbour, Marianne Bilodeau-Bertrand, Ga Eun Lee, Chantal Nelson, Nathalie Auger
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Causes of death in children with birth defects are poorly understood. <h3>Objective</h3> To determine mortality rates by cause of death in children with and without birth defects. <h3>Design, Setting, and Participants</h3> This longitudinal cohort study included a population-based sample of 1 037 688 children and was conducted in all hospitals in Quebec, Canada, with 7 700 596 person-years of follow-up between birth and age 14 years (April 1, 2006, to March 31, 2020). <h3>Exposures</h3> Presence or absence of a birth defect. <h3>Main Outcomes and Measures</h3> Outcomes were all-cause and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were computed for the association between birth defects and mortality with Cox proportional hazards models adjusted for patient characteristics. <h3>Results</h3> Among the 1 037 688 children in the cohort, 95 566 had birth defects (56.5% boys). There were 532 542 boys in the cohort (51.3%), and mean (SD) age at the end of follow-up was 7.42 (3.72) years. There were 918 deaths among children with defects, and the mean (SD) age was 0.93 (2.07) years at death; there were 1082 deaths among the 942 122 children without defects, and the mean (SD) age at death was 0.50 (1.51) years. Mortality rates were higher for children with birth defects compared with no defect (1.3 vs 0.2 deaths per 1000 person-years, respectively). Girls (HR, 5.66; 95% CI, 4.96-6.47) and boys (HR, 4.69; 95% CI, 4.15-5.29) with birth defects had an elevated risk of death before 14 years compared with unaffected children. Birth defects were associated with mortality from circulatory (HR, 26.59; 95% CI, 17.73-39.87), respiratory (HR, 23.03; 95% CI, 15.09-35.14), and digestive causes (HR, 31.77; 95% CI, 11.87-85.04), but anomalies were rarely listed as the cause of death. Compared with children with no defect, those with birth defects were at greatest risk of death between 28 and 364 days of life. <h3>Conclusions and Relevance</h3> This cohort study of 1 037 688 children suggests that birth defects were strongly associated with mortality owing to circulatory, respiratory, and digestive causes. This finding suggests that the contribution of birth defects may be underestimated in mortality statistics.
Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial
Authors: Elise M Meima-van Praag, Kyra L van Rijn, Karin A T G M Wasmann, Harmanna J Snijder, Jaap Stoker, Geert R D'Haens, Krisztina B Gecse, Michael F Gerhards, Jeroen M Jansen, Marcel G W Dijkgraaf, Jarmila D W van der Bilt, Marco W Mundt, Antonino Spinelli, Silvio Danese, Willem A Bemelman, Christianne J Buskens
Journal: The Lancet. Gastroenterology & hepatology (2022)
Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study
Authors: Evan Y. Yu, Michael P. Kolinsky, William R. Berry, Margitta Retz, Loic Mourey, Josep M. Piulats, Leonard J. Appleman, Emanuela Romano, Gwenaelle Gravis, Howard Gurney, Martin Bögemann, Urban Emmenegger, Anthony M. Joshua, Mark Linch, Srikala Sridhar, Henry J. Conter, Brigitte Laguerre, Christophe Massard, Xin Tong Li, Charles Schloss, Christian H. Poehlein, Johann S. de Bono
Journal: European Urology (2022)

Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments. To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC. The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening. Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m2 IV Q3W, and prednisone 5 mg orally twice daily. The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3–modified RECIST v1.1 by BICR; and overall survival (OS). Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3–5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size. Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted. We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.
A traction wire facilitates the pocket-creation method for endoscopic submucosal dissection in the cecum
Authors: Hiroaki Ishii, Hisashi Fukuda, Yoshikazu Hayashi, Takaaki Morikawa, Osamu Taniguchi, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2022)

Although the pocket-creation method (PCM) facilitates colorectal endoscopic submucosal dissection (ESD) [1], novice endoscopists sometime struggle to open the submucosal pocket at the end of the procedure. We previously reported the use of a reopenable clip to facilitate opening of the pocket; the traction provided by the clip allows the submucosa around the pocket to remain stretched [2]. A traction wire (ProdiGI Traction Wire, ERD-TW20, ERD-TW35; Medtronic, Minneapolis, Minnesota, USA) was recently introduced as a unique traction device consisting of a curved wire loop made from a shape-memory alloy with a grasping clip. A lesion can be pulled up by re-curving the traction wire connected between the area of dissection that includes the lesion and the wall behind the lesion. This traction wire can be used in various ways as a traction device [3] [4].
Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis
Authors: Yang Liu, Carl A.B. Pearson, Frank G. Sandmann, Rosanna C. Barnard, Jong-Hoon Kim, Stefan Flasche, Mark Jit, Kaja Abbas
Journal: The Lancet Regional Health - Europe (2022)

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.
Natural language processing applied to mental illness detection: a narrative review
Authors: Tianlin Zhang, Annika M. Schoene, Shaoxiong Ji, Sophia Ananiadou
Journal: npj Digital Medicine (2022)

Abstract Mental illness is highly prevalent nowadays, constituting a major cause of distress in people’s life with impact on society’s health and well-being. Mental illness is a complex multi-factorial disease associated with individual risk factors and a variety of socioeconomic, clinical associations. In order to capture these complex associations expressed in a wide variety of textual data, including social media posts, interviews, and clinical notes, natural language processing (NLP) methods demonstrate promising improvements to empower proactive mental healthcare and assist early diagnosis. We provide a narrative review of mental illness detection using NLP in the past decade, to understand methods, trends, challenges and future directions. A total of 399 studies from 10,467 records were included. The review reveals that there is an upward trend in mental illness detection NLP research. Deep learning methods receive more attention and perform better than traditional machine learning methods. We also provide some recommendations for future studies, including the development of novel detection methods, deep learning paradigms and interpretable models.
Early treatment with sotrovimab monoclonal antibody in kidney transplant recipients with Omicron infection
Authors: Nathalie Chavarot, Clea Melenotte, Lucile Amrouche, Claire Rouzaud, Rebecca Sberro-Soussan, Juliette Pavie, Frank Martinez, Anne Pouvaret, Marianne Leruez-Ville, Delphine Cantin, Jacques Fourgeaud, Claire Delage, Damien Vimpere, Marie Noëlle Peraldi, Christophe Legendre, Fanny Lanternier, Julien Zuber, Anne Scemla, Dany Anglicheau
Journal: Kidney International (2022)
National, regional, and global estimates of anaemia by severity in women and children for 2000–19: a pooled analysis of population-representative data
Authors: Gretchen A Stevens, Christopher J Paciorek, Monica C Flores-Urrutia, Elaine Borghi, Sorrel Namaste, James P Wirth, Parminder S Suchdev, Majid Ezzati, Fabian Rohner, Seth R Flaxman, Lisa M Rogers
Journal: The Lancet Global Health (2022)

BackgroundAnaemia causes health and economic harms. The prevalence of anaemia in women aged 15–49 years, by pregnancy status, is indicator 2.2.3 of the UN Sustainable Development Goals, and the aim of halving the anaemia prevalence in women of reproductive age by 2030 is an extension of the 2025 global nutrition targets endorsed by the World Health Assembly (WHA). We aimed to estimate the prevalence of anaemia by severity for children aged 6–59 months, non-pregnant women aged 15–49 years, and pregnant women aged 15–49 years in 197 countries and territories and globally for the period 2000–19.MethodsFor this pooled analysis of population-representative data, we collated 489 data sources on haemoglobin distribution in children and women from 133 countries, including 4·5 million haemoglobin measurements. Our data sources comprised health examination, nutrition, and household surveys, accessed as anonymised individual records or as summary statistics such as mean haemoglobin and anaemia prevalence. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions in each population and country-year. This model allowed for coherent estimation of mean haemoglobin and prevalence of anaemia by severity.FindingsGlobally, in 2019, 40% (95% uncertainty interval [UI] 36–44) of children aged 6–59 months were anaemic, compared to 48% (45–51) in 2000. Globally, the prevalence of anaemia in non-pregnant women aged 15–49 years changed little between 2000 and 2019, from 31% (95% UI 28–34) to 30% (27–33), while in pregnant women aged 15–49 years it decreased from 41% (39–43) to 36% (34–39). In 2019, the prevalence of anaemia in children aged 6–59 months exceeded 70% in 11 countries and exceeded 50% in all women aged 15–49 years in ten countries. Globally in all populations and in most countries and regions, the prevalence of mild anaemia changed little, while moderate and severe anaemia declined in most populations and geographical locations, indicating a shift towards mild anaemia.InterpretationGlobally, regionally, and in nearly all countries, progress on anaemia in women aged 15–49 years is insufficient to meet the WHA global nutrition target to halve anaemia prevalence by 2030, and the prevalence of anaemia in children also remains high. A better understanding of the context-specific causes of anaemia and quality implementation of effective multisectoral actions to address these causes are needed.FundingUSAID, US Centers for Disease Control and Prevention, and Bill & Melinda Gates Foundation.
Comparable neutralisation evasion of SARS-CoV-2 omicron subvariants BA.1, BA.2, and BA.3
Authors: Prerna Arora, Lu Zhang, Cheila Rocha, Anzhalika Sidarovich, Amy Kempf, Sebastian Schulz, Anne Cossmann, Bernhard Manger, Eva Baier, Björn Tampe, Onnen Moerer, Steffen Dickel, Alexandra Dopfer-Jablonka, Hans-Martin Jäck, Georg M N Behrens, Martin S Winkler, Stefan Pöhlmann, Markus Hoffmann
Journal: The Lancet Infectious Diseases (2022)
Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity
Authors: Rebecca L. McIntyre, Yasmine J. Liu, Man Hu, Brian J. Morris, Bradley J. Willcox, Timothy A. Donlon, Riekelt H. Houtkooper, Georges E. Janssens
Journal: Ageing Research Reviews (2022)

Life expectancy has increased substantially over the last 150 years. Yet this means that now most people also spend a greater length of time suffering from various age-associated diseases. As such, delaying age-related functional decline and extending healthspan, the period of active older years free from disease and disability, is an overarching objective of current aging research. Geroprotectors, compounds that target pathways that causally influence aging, are increasingly recognized as a means to extend healthspan in the aging population. Meanwhile, FOXO3 has emerged as a geroprotective gene intricately involved in aging and healthspan. FOXO3 genetic variants are linked to human longevity, reduced disease risks, and even self-reported health. Therefore, identification of FOXO3-activating compounds represents one of the most direct candidate approaches to extending healthspan in aging humans. In this work, we review compounds that activate FOXO3, or influence healthspan or lifespan in a FOXO3-dependent manner. These compounds can be classified as pharmaceuticals, including PI3K/AKT inhibitors and AMPK activators, antidepressants and antipsychotics, muscle relaxants, and HDAC inhibitors, or as nutraceuticals, including primary metabolites involved in cell growth and sustenance, and secondary metabolites including extracts, polyphenols, terpenoids, and other purified natural compounds. The compounds documented here provide a basis and resource for further research and development, with the ultimate goal of promoting healthy longevity in humans.
Long-term leisure-time physical activity and risk of all-cause and cardiovascular mortality: dose–response associations in a prospective cohort study of 210 327 Taiwanese adults
Authors: David Martinez-Gomez, Veronica Cabanas-Sanchez, Tsung Yu, Fernando Rodriguez-Artalejo, Ding Ding, I-Min Lee, Ulf Ekelund
Journal: British Journal of Sports Medicine (2022)

We aimed to investigate the dose-response associations of long-term leisure-time physical activity (LTPA) obtained from repeated measures with all-cause and cardiovascular disease (CVD) mortality outcomes in Taiwanese adults.We included 210 327 participants with self-reported LTPA at least in two medical examinations (867 968 data points) for up to 20 years (median, IQR: 4.8 years, 2.3-9.0). Dose-response relationships were modelled with restricted cubic spline functions and Cox regressions HRs (95% CIs) adjusted for main covariates.During up to 23 years of follow-up (3 655 734 person-years), 10 539 participants died, of which 1919 of CVD. We observed an inverse, non-linear dose-response association between long-term LTPA and all-cause and CVD mortality. Compared with the referent (0 metabolic equivalent of task (MET) hours/week), insufficient (0.01-7.49 MET hours/week), recommended (7.50-15.00 MET hours/week) and additional (>15 MET hours/week) amounts of LTPA had a lower mortality risk of 0.74 (0.69-0.80), 0.64 (0.60-0.70) and 0.59 (0.54-0.64) for all-cause mortality and 0.68 (0.60-0.84), 0.56 (0.47-0.67) and 0.56 (0.47-0.68) for CVD mortality. When using only baseline measures of LTPA, the corresponding mortality risk was 0.88 (0.84-0.93), 0.83 (0.78-0.88) and 0.78 (0.73-0.83) for all-cause and 0.91 (0.81-1.02), 0.78 (0.68-0.89) and 0.80 (0.70-0.92) for CVD mortality.Long-term LTPA was associated with lower risks of all-cause and CVD mortality. The magnitude of risk reductions was larger when modelling repeated measures of LTPA compared with one measure of LTPA at baseline.
Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology
Authors: John A. Thompson, Bryan J. Schneider, Julie Brahmer, Amaka Achufusi, Philippe Armand, Meghan K. Berkenstock, Shailender Bhatia, Lihua E. Budde, Saurin Chokshi, Marianne Davies, Amro Elshoury, Yaron Gesthalter, Aparna Hegde, Michael Jain, Benjamin H. Kaffenberger, Melissa G. Lechner, Tianhong Li, Alissa Marr, Suzanne McGettigan, Jordan McPherson, Theresa Medina, Nisha A. Mohindra, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Pradnya Patil, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Yinghong Wang, Vlad G. Zaha, Megan Lyons, Mary Dwyer, Lisa Hang
Journal: Journal of the National Comprehensive Cancer Network (2022)

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org .