tbuckley/cabot-search huggingface dataset:
Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)
Authors: Yuankai Shi, Jianqiu Wu, Zhen Wang, Liling Zhang, Zhao Wang, Mingzhi Zhang, Hong Cen, Zhigang Peng, Yufu Li, Lei Fan, Ye Guo, Liping Ma, Jie Cui, Yuhuan Gao, Haiyan Yang, Hongyu Zhang, Lin Wang, Weihua Zhang, Huilai Zhang, Liping Xie, Ming Jiang, Hui Zhou, Yuerong Shuang, Hang Su, Xiaoyan Ke, Chuan Jin, Xin Du, Xin Du, Li Liu, Yaming Xi, Zheng Ge, Ru Feng, Yang Zhang, Shengyu Zhou, Fan Xie, Qian Wang
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to &lt; 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased ( n = 4) and platelet count decreased ( n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration : This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.
Tobacco control and the ERS: new problems and old foes
Authors: Jonathan Grigg
Journal: European Respiratory Journal (2021)

<b>A review of future tasks of the ERS Tobacco Control Committee from the incoming chair: e-cigarettes and novel heated tobacco products, preventing the uptake of cigarettes, advocating basic smoking cessation measures, and learning from the COVID-19 pandemic</b>https://bit.ly/3nvC6eT
Abstract 17379: Prevalence and Significance of Unrecognized Renal Dysfunction in Patients With Stroke
Authors: David Pereg, Zach Rozenbaum, Dina Vorobeichik, David Tanne
Journal: Circulation (2016)

Introduction: Unrecognized renal dysfunction, defined as estimated glomerular filtration rate <60ml/min1.73m2 in the presence of normal serum creatinine levels, is a common co-morbidity among patie...
OFP01.01 Liquid Biopsy to Detect MET Alterations in Patients with Advanced NSCLC: Biomarker Analysis from the VISION Study
Authors: X. Le, D. Kowalski, B.C. Cho, P. Conte, E. Felip, M. Garassino, S. Viteri, G.-C. Chang, J. Richart, L. Paz-Ares, D. Juraeva, J. Straub, C. Stroh, P. Paik
Journal: Journal of Thoracic Oncology (2021)
Is chronic nonspecific pleuritis truly nonspecific?: a morphometric study in biopsies wit emphasis on the differential diagnosis
Authors: Vera Luiza Capelozzi, L. Antonângelo, A. Logulo, T. S. Carvalhos, J. V. Barbars Filho, Carlos Roberto Ribeiro de Carvalho, P. H. N. Saldiva, D. Deheinzelin
Journal: American Journal of Respiratory and Critical Care Medicine (1996)
Methodological quality of studies evaluating the burden of drug-resistant infections in humans due to the WHO Global Antimicrobial Resistance Surveillance System target bacteria
Authors: Maria Diletta Pezzani, Barbara Tornimbene, Carmem Pessoa-Silva, Marlieke de Kraker, Sebastiano Rizzardo, Nicola Duccio Salerno, Stephan Harbarth, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2021)

The health impact of antimicrobial resistance (AMR) has not been included in the Global Burden of Disease (GBD) report, as reliable data have been lacking. AMR burden estimates have been derived from models combining incidence and/or prevalence data from national and/or international surveillance systems and mortality estimates from clinical studies. Depending on utilized empirical data, statistical methodology and applied endpoints, the validity and reliability of results can differ substantially.
Hemchandra Kanji Mehta
Authors: Kathir Puvana Chandra
Journal: BMJ (2021)

Hemchandra Kanji Mehta (“Hemant”) was born in Gujarat, India, where his father was the personal tutor to the prince, but when the need at the palace changed and India’s great depression of 1931 set in, the family moved to Tanzania (then Tanganyika) when Hemant was just 6 months old. His father took up a post as a headmaster of a school, and Hemant spent his early formative years there along with his five siblings. He returned to India for higher studies, where he excelled academically and in sports. He played cricket for the University of Baroda and qualified as a doctor with honours from Grant Medical College, Bombay. He met and married Min, a fellow medical undergraduate at the Baroda Medical College . They both moved to UK for postgraduate training. Hemant trained to be an ophthalmologist and Min a gynaecologist.

Hemant’s academic achievements as an undergraduate and his hard work gave him the opportunity to train …
Serine Biosynthesis Is a Metabolic Vulnerability in FLT3-ITD–Driven Acute Myeloid Leukemia
Authors: Stefan Bjelosevic, Emily Gruber, Andrea Newbold, Carolyn Shembrey, Jennifer R. Devlin, Simon J. Hogg, Lev Kats, Izabela Todorovski, Zheng Fan, Thomas C. Abrehart, Giovanna Pomilio, Andrew Wei, Gareth P. Gregory, Stephin J. Vervoort, Kristin K. Brown, Ricky W. Johnstone
Journal: Cancer Discovery (2021)

Abstract Internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITD) occurs in 30% of all acute myeloid leukemias (AML). Limited clinical efficacy of FLT3 inhibitors highlights the need for alternative therapeutic modalities in this subset of disease. Using human and murine models of FLT3-ITD–driven AML, we demonstrate that FLT3-ITD promotes serine synthesis and uptake via ATF4-dependent transcriptional regulation of genes in the de novo serine biosynthesis pathway and neutral amino acid transport. Genetic or pharmacologic inhibition of PHGDH, the rate-limiting enzyme of de novo serine biosynthesis, selectively inhibited proliferation of FLT3-ITD AMLs in vitro and in vivo. Moreover, pharmacologic inhibition of PHGDH sensitized FLT3-ITD AMLs to the standard-of-care chemotherapeutic cytarabine. Collectively, these data reveal novel insights into FLT3-ITD–induced metabolic reprogramming and reveal a targetable vulnerability in FLT3-ITD AML. Significance: FLT3-ITD mutations are common in AML and are associated with poor prognosis. We show that FLT3-ITD stimulates serine biosynthesis, thereby rendering FLT3-ITD–driven leukemias dependent upon serine for proliferation and survival. This metabolic dependency can be exploited pharmacologically to sensitize FLT3-ITD–driven AMLs to chemotherapy. This article is highlighted in the In This Issue feature, p. 1307
Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis
Authors: Gabriel Mezzano, Adria Juanola, Andres Cardenas, Esteban Mezey, James P Hamilton, Elisa Pose, Isabel Graupera, Pere Ginès, Elsa Solà, Ruben Hernaez
Journal: Gut (2021)

Background and aims Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures. Methods We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses. Results We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates. Conclusions The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.
Obstructive Sleep Apnea: A Respiratory Syndrome With Protean Cardiovascular Manifestations⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Ian Wilcox, Christopher Semsarian
Journal: Journal of the American College of Cardiology (2009)
Clinical Impact of Pathological Features Including the Ki-67 Labeling Index on Diagnosis and Prognosis of Adult and Pediatric Adrenocortical Tumors
Authors: Sebastiao N. Martins-Filho, Madson Q. Almeida, Ibere Soares, Alda Wakamatsu, Venancio Avancini F. Alves, Maria Candida Barisson V. Fragoso, Maria Claudia N. Zerbini
Journal: Endocrine Pathology (2021)
An interpretable bimodal neural network characterizes the sequence and preexisting chromatin predictors of induced transcription factor binding
Authors: Divyanshi Srivastava, Begüm Aydin, Esteban O. Mazzoni, Shaun Mahony
Journal: Genome biology (2021)

Abstract Background Transcription factor (TF) binding specificity is determined via a complex interplay between the transcription factor’s DNA binding preference and cell type-specific chromatin environments. The chromatin features that correlate with transcription factor binding in a given cell type have been well characterized. For instance, the binding sites for a majority of transcription factors display concurrent chromatin accessibility. However, concurrent chromatin features reflect the binding activities of the transcription factor itself and thus provide limited insight into how genome-wide TF-DNA binding patterns became established in the first place. To understand the determinants of transcription factor binding specificity, we therefore need to examine how newly activated transcription factors interact with sequence and preexisting chromatin landscapes. Results Here, we investigate the sequence and preexisting chromatin predictors of TF-DNA binding by examining the genome-wide occupancy of transcription factors that have been induced in well-characterized chromatin environments. We develop Bichrom, a bimodal neural network that jointly models sequence and preexisting chromatin data to interpret the genome-wide binding patterns of induced transcription factors. We find that the preexisting chromatin landscape is a differential global predictor of TF-DNA binding; incorporating preexisting chromatin features improves our ability to explain the binding specificity of some transcription factors substantially, but not others. Furthermore, by analyzing site-level predictors, we show that transcription factor binding in previously inaccessible chromatin tends to correspond to the presence of more favorable cognate DNA sequences. Conclusions Bichrom thus provides a framework for modeling, interpreting, and visualizing the joint sequence and chromatin landscapes that determine TF-DNA binding dynamics.
Clinical Proteomics of Metastatic Melanoma Reveals Profiles of Organ Specificity and Treatment Resistance
Authors: Lir Beck, Michal Harel, Shun Yu, Ettai Markovits, Ben Boursi, Gal Markel, Tamar Geiger
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Treatment of metastatic melanoma has dramatically improved in recent years, thanks to the development of immunotherapy and BRAF-MEK–targeted therapies. However, these developments revealed marked heterogeneity in patient response, which is yet to be fully understood. In this work, we aimed to associate the proteomic profiles of metastatic melanoma with the patient clinical information, to identify protein correlates with metastatic location and prior treatments. Experimental Design: We performed mass spectrometry–based proteomic analysis of 185 metastatic melanoma samples and followed with bioinformatics analysis to examine the association of metastatic location, BRAF status, survival, and immunotherapy response with the tumor molecular profiles. Results: Bioinformatics analysis showed a high degree of functional heterogeneity associated with the site of metastasis. Lung metastases presented higher immune-related proteins, and higher mitochondrial-related processes, which were shown previously to be associated with better immunotherapy response. In agreement, epidemiological analysis of data from the National Cancer Database showed improved response to anti-programmed death 1, mainly in patients with lung metastasis. Focus on lung metastases revealed prognostic and molecular heterogeneity and highlighted potential tissue-specific biomarkers. Analysis of the BRAF mutation status and prior treatments with MAPK inhibitors proposed the molecular basis of the effect on immunotherapy response and suggested coordinated combination of immunotherapy and targeted therapy may increase treatment efficacy. Conclusions: Altogether, the proteomic data provided novel molecular determinants of critical clinical features, including the effects of sequential treatments and metastatic locations. These results can be the basis for development of site-specific treatments toward treatment personalization.
OFP01.08 Tolerability, Low-Fat Meal Effect, and Relative Bioavailability (BA) of Oral EGFR Inhibitor TAK-788 in Healthy Volunteers
Authors: S. Zhang, S. Jin, C. Griffin, Z. Feng, J. Lin, R. Brake, K. Venkatakrishnan, N. Gupta
Journal: Journal of Thoracic Oncology (2021)
American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline for Management of Hereditary Breast Cancer
Authors: Cheng-Har Yip, Lisa A. Newman
Journal: JAMA Surgery (2021)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 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 Surgery journal
Antiemetic Drugs During Pregnancy: What Can We Learn From Spontaneous Reporting System Database Analyses?
Authors: Faizan Mazhar, Vera Battini, Carla Carnovale
Journal: JAMA Pediatrics (2021)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Re: Fredrik Liedberg, Petter Kollberg, Marie Allerbo, et al. Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh: A Randomised Study. Eur Urol 2020;78:757–63
Authors: Amit Bansal, Ruchir Maheshwari, Anant Kumar
Journal: European Urology (2021)
Prognostic Significance of Pretreatment 18F-FDG PET/CT Volumetric Parameters in Patients With Colorectal Liver Metastasis
Authors: Yong-il Kim, Hyo Sang Lee, Joon Young Choi
Journal: Clinical Nuclear Medicine (2021)

Purpose Colorectal liver metastasis (CRLM) remains a clinical challenge due to the lack of reliable prognostic parameters. We performed a systematic review and meta-analysis of the prognostic value of pretreatment 18 F-FDG PET/CT volumetric parameters for hepatic metastatic lesions (HMLs) in patients with CRLM. Methods A systematic search was performed using the following combination of keywords: CRLM, FDG, PET, and prognosis. The inclusion criteria were studies using 18 F-FDG PET/CT as an imaging tool before treatment, including volumetric parameters (metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) for HMLs, and reported survival data. Event-free survival and overall survival were considered as survival markers. The effect on survival was determined by the effect size of the hazard ratio (HR) with 95% confidence interval (CI). Results Our systematic search identified 668 records, and a total of 10 studies comprising 494 patients were included. The pooled HRs of the prognostic value of the MTV and TLG for event-free survival were 1.55 (95% CI, 1.21–1.99; P = 0.0006) and 1.64 (95% CI, 1.23–2.19; P = 0.0009) with significance, respectively. The pooled HRs of the prognostic value of the MTV and TLG for overall survival were 1.72 (95% CI, 1.32–2.23; P &lt; 0.0001) and 2.09 (95% CI, 1.48–2.96; P &lt; 0.0001) with significance, respectively. Conclusions Higher MTV and TLG for HMLs before treatment were identified as worse prognostic parameters in patients with CRLM. The MTV and TLG of 18 F-FDG PET/CT could be used as predictors of prognosis.
Associations Between Simulated Future Changes in Climate, Air Quality, and Human Health
Authors: Neal L. Fann, Christopher G. Nolte, Marcus C. Sarofim, Jeremy Martinich, Nicholas J. Nassikas
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Future changes in climate are likely to adversely affect human health by affecting concentrations of particulate matter sized less than 2.5 μm (PM<sub>2.5</sub>) and ozone (O<sub>3</sub>) in many areas. However, the degree to which these outcomes may be mitigated by reducing air pollutant emissions is not well understood. <h3>Objective</h3> To model the associations between future changes in climate, air quality, and human health for 2 climate models and under 2 air pollutant emission scenarios. <h3>Design, Setting, and Participants</h3> This modeling study simulated meteorological conditions over the coterminous continental US during a 1995 to 2005 baseline and over the 21st century (2025-2100) by dynamically downscaling representations of a high warming scenario from the Community Earth System Model (CESM) and the Coupled Model version 3 (CM3) global climate models. Using a chemical transport model, PM<sub>2.5</sub>and O<sub>3</sub>concentrations were simulated under a 2011 air pollutant emission data set and a 2040 projection. The changes in PM<sub>2.5</sub>and O<sub>3</sub>-attributable deaths associated with climate change among the US census-projected population were estimated for 2030, 2050, 2075, and 2095 for each of 2 emission inventories and climate models. Data were analyzed from June 2018 to June 2020. <h3>Main Outcomes and Measures</h3> The main outcomes were simulated change in summer season means of the maximum daily 8-hour mean O<sub>3</sub>, annual mean PM<sub>2.5</sub>, population-weighted exposure, and the number of avoided or incurred deaths associated with these pollutants. Results are reported for 2030, 2050, 2075, and 2095, compared with 2000, for 2 climate models and 2 air pollutant emissions data sets. <h3>Results</h3> The projected increased maximum daily temperatures through 2095 were up to 7.6 °C for the CESM model and 11.8 °C for the CM3 model. Under each climate model scenario by 2095, compared with 2000, an estimated additional 21 000 (95% CI, 14 000-28 000) PM<sub>2.5</sub>-attributable deaths and 4100 (95% CI, 2200-6000) O<sub>3</sub>-attributable deaths were projected to occur. These projections decreased to an estimated 15 000 (95% CI, 10 000-20 000) PM<sub>2.5</sub>-attributable deaths and 640 (95% CI, 340-940) O<sub>3</sub>-attributable deaths when simulated using a future emission inventory that accounted for reduced anthropogenic emissions. <h3>Conclusions and Relevance</h3> These findings suggest that reducing future air pollutant emissions could also reduce the climate-driven increase in deaths associated with air pollution by hundreds to thousands.
OA03.02 Nivolumab (NIVO) + ipilimumab (IPI) + 2 Cycles of Platinum-Doublet Chemotherapy (Chemo) vs. 4 Cycles Chemo as First-Line (1L) Treatment) for Stage IV/Recurrent Non-Small Cell Lung Cancer (NSCLC): CheckMate 9LA
Authors: M. Reck, T.-E. Ciuleanu, M.C. Dols, M. Schenker, B. Zurawski, J. Menezes, E. Richardet, J. Bennouna, E. Felip, O.J. Vidal, A. Alexandru, H. Sakai, A. Scherpereel, S. Lu, T. John, D.P. Carbone, S. Meadows-Shropshire, J. Yan, L.G. Paz-Ares
Journal: Journal of Thoracic Oncology (2021)
Covid-19: Health and social care staff must be vaccinated now, says BMA
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Covid-19: Health and social care staff must be vaccinated now, says BMA Zosia KmietowiczThe BMA has made an urgent call for all health and social care workers to be vaccinated by the end of January and for those at greatest risk of contracting covid-19 to be vaccinated within two weeks.It said that this was essential, to protect an already depleted workforce and to help prevent the NHS becoming overwhelmed in the next three weeks.