tbuckley/cabot-search huggingface dataset:
Need for More Comprehensive Evaluation of Immune-Related Adverse Events in Immunotherapy for Biliary Tract Cancer—Reply
Authors: Dae Won Kim, Michael J. Schell, Richard D. Kim
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection
Authors: Zheng Zhong, Xiaoqian Deng, Pengrui Wang, Claire Yu, Wisarut Kiratitanaporn, Xiaokang Wu, Jacob Schimelman, Min Tang, Alis Balayan, Emmie Yao, Jing Tian, Luwen Chen, Kang Zhang, Shaochen Chen
Journal: Biomaterials (2020)
Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants
Authors: John L. Lyles, Lisa J. Martin, Tetsuo Shoda, Margaret H. Collins, Michael P. Trimarchi, Hua He, Leah C. Kottyan, Vincent A. Mukkada, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2020)
Assessment of Value of Neighborhood Socioeconomic Status in Models That Use Electronic Health Record Data to Predict Health Care Use Rates and Mortality
Authors: Alejandro Schuler, Liam O’Súilleabháin, Gina Rinetti-Vargas, Patricia Kipnis, Fernando Barreda, Vincent X Liu, Oleg Sofrygin, Gabriel J. Escobar
Journal: JAMA Network Open (2020)

Prediction models are widely used in health care as a way of risk stratifying populations for targeted intervention. Most risk stratification has been done using a small number of predictors from insurance claims. However, the utility of diverse nonclinical predictors, such as neighborhood socioeconomic contexts, remains unknown.To assess the value of using neighborhood socioeconomic predictors in the context of 1-year risk prediction for mortality and 6 different health care use outcomes in a large integrated care system.Diagnostic study using data from all adults age 18 years or older who had Kaiser Foundation Health Plan membership and/or use in the Kaiser Permantente Northern California: a multisite, integrated health care delivery system between January 1, 2013, and June 30, 2014. Data were recorded before the index date for each patient to predict their use and mortality in a 1-year post period using a test-train split for model training and evaluation. Analyses were conducted in fall of 2019.One-year encounter counts (doctor office, virtual, emergency department, elective hospitalizations, and nonelective), total costs, and mortality.A total of 2 951 588 patients met inclusion criteria (mean [SD] age, 47.2 [17.4] years; 47.8% were female). The mean (SD) Neighborhood Deprivation Index was -0.32 (0.84). The areas under the receiver operator curve ranged from 0.71 for emergency department use (using the LASSO method and electronic health record predictors) to 0.94 for mortality (using the random forest method and electronic health record predictors). Neighborhood socioeconomic status predictors did not meaningfully increase the predictive performance of the models for any outcome.In this study, neighborhood socioeconomic predictors did not improve risk estimates compared with what is obtainable using standard claims data regardless of model used.
Aging-relevant human basal forebrain cholinergic neurons as a cell model for Alzheimer’s disease
Authors: Shuaipeng Ma, Tong Zang, Meng-Lu Liu, Chun-Li Zhang
Journal: Molecular Neurodegeneration (2020)

Abstract Background Alzheimer’s disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics. Recent studies demonstrate that induced neurons directly reprogrammed from adult human skin fibroblasts retain aging-associated features. However, human induced BFCNs (hiBFCNs) have yet to be achieved. Methods We examined a reprogramming procedure for the generation of aging-relevant hiBFCNs through virus-mediated expression of fate-determining transcription factors. Skin fibroblasts were obtained from healthy young persons, healthy adults and sporadic AD patients. Properties of the induced neurons were examined by immunocytochemistry, qRT-PCR, western blotting, and electrophysiology. Results We established a protocol for efficient generation of hiBFCNs from adult human skin fibroblasts. They show electrophysiological properties of mature neurons and express BFCN-specific markers, such as CHAT, p75NTR, ISL1, and VACHT. As a proof-of-concept, our preliminary results further reveal that hiBFCNs from sporadic AD patients exhibit time-dependent TAU hyperphosphorylation in the soma and dysfunctional nucleocytoplasmic transport activities. Conclusions Aging-relevant BFCNs can be directly reprogrammed from human skin fibroblasts of healthy adults and sporadic AD patients. They show promises as an aging-relevant cell model for understanding AD pathology and may be employed for therapeutics identification for AD.
Authors’ reply to Caesar and colleagues, Thornton, Kemple, and Singh
Authors: Victoria Tzortziou Brown, Margaret McCartney, Carl Heneghan
Journal: BMJ (2020)

We thank Caesar and colleagues, Thornton, Kemple, and Singh for their letters to our analysis.12345

We were as perplexed as Goh6 by the references used by Caesar and colleagues in their response7 to support their arguments. The studies quoted do not provide objective evidence on the benefits of appraisal and revalidation for doctors and patients. Archer et al, in their independent evaluation, state: “We found no significant changes …
Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism
Authors: Shuaishuai Xing, Qi Li, Baichen Xiong, Yao Chen, Feng Feng, Wenyuan Liu, Haopeng Sun
Journal: Medicinal Research Reviews (2020)

Abstract Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe and effective in treating organophosphorus (OPs) poisoning and has completed Phase 1 and 2 pharmacokinetic (PK) and safety studies. The introduction of specific mutations into native BChE to endow it a self‐reactivating property has gained much progress in producing effective OPs hydrolases. The hydrolysis ability of native BChE on cocaine has been confirmed but was blocked to clinical application due to poor PK properties. Several BChE mutants with elevated cocaine hydrolysis activity were published, some of which have shown safety and efficiency in treating cocaine addiction of human. The increased level of BChE in progressed Alzheimer's disease patients made it a promising target to elevate acetylcholine level and attenuate cognitive status. A variety of selective BChE inhibitors with high inhibitory activity published in recent years are reviewed here. BChE could influence the weight and insulin secretion and resistance of BChE knockout (KO) mice through hydrolyzing ghrelin. The BChE‐ghrelin pathway could also regulate aggressive behaviors of BChE‐KO mice.
Electronic DNA Analysis of CSF Cell-free Tumor DNA to Quantify Multi-gene Molecular Response in Pediatric High-grade Glioma
Authors: Amy K. Bruzek, Karthik Ravi, Ashwath Muruganand, Jack Wadden, Clarissa May Babila, Evan Cantor, Leo Tunkle, Kyle Wierzbicki, Stefanie Stallard, Robert P. Dickson, Ian Wolfe, Rajen Mody, Jonathan Schwartz, Andrea Franson, Patricia L. Robertson, Karin M. Muraszko, Cormac O. Maher, Hugh J.L. Garton, Tingtin Qin, Carl Koschmann
Journal: Clinical Cancer Research (2020)

Pediatric high-grade glioma (pHGG) diagnosis portends poor prognosis and therapeutic monitoring remains difficult. Tumors release cell-free tumor DNA (cf-tDNA) into cerebrospinal fluid (CSF), allowing for potential detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of cf-tDNA with a handheld platform (Oxford Nanopore MinION) could quantify patient-specific CSF cf-tDNA variant allele fraction (VAF) with improved speed and limit of detection compared with established methods.We performed ultra-short fragment (100-200 bp) PCR amplification of cf-tDNA for clinically actionable alterations in CSF and tumor samples from patients with pHGG (n = 12) alongside nontumor CSF (n = 6). PCR products underwent rapid amplicon-based sequencing by Oxford Nanopore Technology (Nanopore) with quantification of VAF. Additional comparison to next-generation sequencing (NGS) and droplet digital PCR (ddPCR) was performed.Nanopore demonstrated 85% sensitivity and 100% specificity in CSF samples (n = 127 replicates) with 0.1 femtomole DNA limit of detection and 12-hour results, all of which compared favorably with NGS. Multiplexed analysis provided concurrent analysis of H3.3A (H3F3A) and H3C2 (HIST1H3B) mutations in a nonbiopsied patient and results were confirmed by ddPCR. Serial CSF cf-tDNA sequencing by Nanopore demonstrated correlation of radiological response on a clinical trial, with one patient showing dramatic multi-gene molecular response that predicted long-term clinical response.Nanopore sequencing of ultra-short pHGG CSF cf-tDNA fragments is feasible, efficient, and sensitive with low-input samples thus overcoming many of the barriers restricting wider use of CSF cf-tDNA diagnosis and monitoring in this patient population.
CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc
Authors: Shuying Shen, Teng Yao, Yining Xu, Deguang Zhang, Shunwu Fan, Jianjun Ma
Journal: Molecular Cancer (2020)

Osteosarcoma (OS) is the most common malignant bone tumor and has a poor prognosis. The potential involvement of circular RNAs (circRNAs) in OS progression remains unexplored. Here, we report that CircECE1, a circular RNA derived from human ECE1, plays a critical role in energy metabolism in OS.The RIP chip sequence assay was performed to confirm CircECE1, through overexpression or knockdown of CircECE1 to verify its function in 143B and U2OS. RNA immunoprecipitation and immunoprecipitation were used to verify CircECE1's regulation of protein c-Myc and co- immunoprecipitation was used to verified the competitive binding relationship between CircECE1 and SPOP. The influence of CircECE1 on energy metabolism was evaluated by seahorse experiment, western blot, and immunohistochemistry.We found that CircECE1 is highly expressed in OS tissues and cells and that CircECE1 knockdown suppresses tumor proliferation and metastasis both in vitro and in vivo. Further, CircECE1 significantly promotes glucose metabolism in OS cells in vitro and in vivo. Mechanistically, CircECE1 interacts with c-Myc to prevent speckle-type POZ-mediated c-Myc ubiquitination and degradation. C-Myc inhibits thioredoxin binding protein (TXNIP) transcription and subsequently activates the Warburg effect.CircECE1 regulates the Warburg effect through the c-Myc/TXNIP axis. CircECE1 mediated signal transduction plays a important role in OS process and energy metabolism. These findings may identify novel targets for OS molecular therapy.
TCT CONNECT-16 Implications of Impaired Coronary Flow on the Effects of Intracoronary Alteplase During Primary Percutaneous Coronary Intervention
Authors: Annette Maznyczka, Peter McCartney, Patrycja Duklas, John Greenwood, Douglas Muir, Saqib Chowdhary, Nick Curzen, Margaret McEntegart, Keith Oldroyd, Anthony Gershlick, Clare Appleby, Campbell Tait, James Cotton, Andrew Wragg, Naveed Sattar, Keith Fox, Hany Eteiba, Alex McConnachie, Colin Berry
Journal: Journal of the American College of Cardiology (2020)
Intraperitoneal aerosolized drug delivery: Technology, recent developments, and future outlook
Authors: Mohammad Rahimi-Gorji, Leen Van de Sande, Charlotte Debbaut, Ghader Ghorbaniasl, Helena Braet, Sarah Cosyns, Katrien Remaut, Wouter Willaert, Wim Ceelen
Journal: Advanced Drug Delivery Reviews (2020)
Charles E. Egwuagu: Going with the flow
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2020)

Charles E. Egwuagu is an epidemiologist/immunologist and chief of the Molecular Immunology Section at the National Eye Institute, National Institutes of Health, Bethesda, MD. His laboratory is focused on understanding the role played by lymphocytes in autoimmune diseases of the central nervous system. I chatted with Charles about his career so far.
TCT CONNECT-125 TAVR With a Supra-Annular, Self-Expandable Valve in Intermediate Risk Patients: Follow-Up From the SURTAVI Randomized Trial and Continued Access Registry
Authors: Paul Mahoney, Hemal Gada, Hasan Jilaihawi, Ron Waksman, Michael Reardon
Journal: Journal of the American College of Cardiology (2020)
Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis
Authors: Evan S. Dellon, Kathryn A. Peterson, Joseph A. Murray, Gary W. Falk, Nirmala Gonsalves, Mirna Chehade, Robert M. Genta, John Leung, Paneez Khoury, Amy D. Klion, Sabine Hazan, Michael Vaezi, Adam C. Bledsoe, Sandy R. Durrani, Chao Wang, Camilla Shaw, Alan T. Chang, Bhupinder Singh, Amol P. Kamboj, Henrik S. Rasmussen, Marc E. Rothenberg, Ikuo Hirano
Journal: New England Journal of Medicine (2020)

Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).
Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults
Authors: Robin Foà, Renato Bassan, Antonella Vitale, Loredana Elia, Alfonso Piciocchi, Maria-Cristina Puzzolo, Martina Canichella, Piera Viero, Felicetto Ferrara, Monia Lunghi, Francesco Fabbiano, Massimiliano Bonifacio, Nicola Fracchiolla, Paolo Di Bartolomeo, Alessandra Mancino, Maria-Stefania De Propris, Marco Vignetti, Anna Guarini, Alessandro Rambaldi, Sabina Chiaretti
Journal: New England Journal of Medicine (2020)

Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.).
TCT CONNECT-38 Mechanical Complications in ST-Segment Elevation Myocardial Infarction Based on Reperfusion Strategy: A Nationwide Trends Analysis
Authors: Byomesh Tripathi, Ankur Kalra, Jay Giri, Partha Sardar, Dharam Kumbhani, Saurav Chatterjee
Journal: Journal of the American College of Cardiology (2020)
The Early Burden of Disability in Individuals With Mood and Other Common Mental Disorders in Ontario, Canada
Authors: Benicio N. Frey, Simone Vigod, Taiane de Azevedo Cardoso, Diego Librenza-Garcia, Lindsay Favotto, Richard Perez, Flavio Kapczinski
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Large population-based data on the trajectory to disability after the first diagnosis of a mood disorder are lacking. <h3>Objective</h3> To assess the time between an incident mood disorder diagnosis and the receipt of disability services during a follow-up period of as long as 20 years. <h3>Design, Setting, and Participants</h3> This cohort study used health administrative and social service data from ICES for 1 902 792 adults aged 18 to 59 years living in Ontario, Canada. A narrow cohort of individuals who had a new diagnosis of a mood disorder between October 1, 1997, and March 31, 2007, matched by sex and age to individuals with no history of mood disorder, included 278 296 participants. A broader cohort of individuals who had a new diagnosis of other common mental disorders during the same period, matched by sex and age to individuals with no history of mental disorder diagnosis, included 1 624 496 individuals. All individuals were followed up to a maximum end date of March 31, 2017. Data analysis was conducted from November 2017 to June 2018. <h3>Exposure</h3> Incident diagnosis of mood or common mental disorder. <h3>Main Outcomes and Measures</h3> Disability outcomes were as follows: (1) entry into the Ontario Disability Support Program (ODSP), signifying long-term inability to work because of a disability, and (2) admission into a long-term care (LTC) residence, signifying the inability to live in independent housing. Cox proportional hazards models were used. <h3>Results</h3> In the full cohort of 1 902 792 individuals, 278 296 participants (14.6%) were included in the mood disorder cohort (mean [SD] age, 37.5 [11.9] years; 157 386 [56.6%] women), and 1 624 496 participants (85.4%) were included in the common mental disorder cohort (mean [SD], 36.5 [11.8] years; 932 545 [57.4%] women). The incidence of ODSP initiation was greater among individuals with mood disorders than those without (51.5 per 10 000 person-years vs 25.5 per 10 000 person-years; adjusted hazard ratio [aHR], 2.03; 95% CI, 1.95-2.11) and for those with common mental disorders (45.0 per 10 000 person-years vs 27.6 per 10 000 person-years; aHR, 1.57; 95% CI, 1.55-1.60). The aHR for admission to LTC was also higher among individuals with mood disorders compared with those without (aHR, 2.20; 95% CI, 1.80-2.69) and those with common mental disorders compared with those without (aHR, 1.21; 95% CI, 1.14-1.29). Individuals with bipolar disorders had greater ODSP rates than individuals with major depressive disorders (crude rate ratio: 4.31 [95% CI, 3.56-5.17] vs 1.82 [95% CI, 1.36-2.43]). <h3>Conclusions and Relevance</h3> This cohort study found that mood disorders were associated with elevated and early rates of disability services. Effective early intervention strategies targeting functional impairment in this population are encouraged.