tbuckley/cabot-search huggingface dataset:
Role of Rotavirus Vaccination in Decline in Incidence of Type 1 Diabetes
Authors: Mary Ellen Vajravelu, Jaclyn Tamaroff, Justine Shults
Journal: JAMA Pediatrics (2019)

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
LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer
Authors: Ramona Rudalska, Jule Harbig, Marteinn T. Snaebjornsson, Sabrina Klotz, Stefan Zwirner, Liudmyla Taranets, Florian Heinzmann, Thales Kronenberger, Michael Forster, Wei Cui, Luana D’Artista, Elias Einig, Martina Hinterleitner, Werner Schmitz, Agata Dylawerska, Tae-Won Kang, Antti Poso, Mathias T. Rosenfeldt, Nisar P. Malek, Michael Bitzer, Stefan Laufer, Bernd J. Pichler, Nikita Popov, Almut Schulze, Lars Zender, Daniel Dauch
Journal: Nature Cancer (2021)
Prevalence of PD-L1 expression in first-line (1L) locally advanced/unresectable or metastatic urothelial carcinoma (UC).
Authors: Petros Grivas, Alicia K. Morgans, Yair Lotan, Jeffrey P. Gregg, Daniel M. Geynisman, Terence W. Friedlander, Piyush K. Agarwal, Marija Tesic-Schnell, Andrew Bernstein, Doris Makari, Joshua J Meeks
Journal: Journal of Clinical Oncology (2019)

TPS67 Background: Treatments for 1L advanced/metastatic UC include platinum-based chemotherapy, an immune checkpoint inhibitor (ICI) or clinical trial enrollment. Not all patients benefit from, or are eligible for, specific therapies due to comorbidities and performance status. There is an urgent need for biomarker-directed strategies to enable patient selection and improve outcomes. Currently the only clinically used molecular biomarker is PD-L1 protein expression in tumor tissue. Although inconsistent and variable among assays, higher PD-L1 expression generally correlates with increased ICI response rate. Improved understanding of the prevalence and potential prognostic and/or predictive role of PD-L1 can further enhance its clinical utility and guide novel clinical trial designs. Methods: This observational study will enroll 250 patients with advanced UC prior to starting or during 1L therapy, as initiated at the discretion of participating clinicians, from 60 US community sites. The primary endpoint is prevalence of PD-L1 expression by VENTANA SP263 Assay (exact [Clopper-Pearson] 95% CI) on pre-treatment tumor tissue. Secondary endpoints include the association of pre-treatment PD-L1 expression with pre-treatment tumor tissue mutational burden (tTMB), descriptions of treatment response and outcomes (ORR based on RECIST 1.1, PFS, OS) and assessment of their correlations with PD-L1 expression. Exploratory endpoints include the association of pre-treatment tumor tissue PD-L1 with pre-treatment blood-based tumor mutational burden (bTMB), changes in circulating tumor DNA (ctDNA) levels at various timepoints, the correlation between tTMB and bTMB values, and the association of those biomarkers for outcomes of PFS and OS. Enrollment will take place over 24 months with follow-up to 30 months from study enrollment. With 250 patients, the 95% CI for 30%, 45%, and 60% observed prevalence of PD-L1 high are (24.4%, 36.1%), (38.9%, 51.2%), and (53.6%, 66.1%), respectively; the various secondary and exploratory analyses will be descriptive.
Three Critical Questions That Should Be Asked Before Using Prediction Models for Clinical Decision Support
Authors: Alex H. S. Harris
Journal: JAMA Network Open (2019)

Muhammad Ali Chaudhary, MD; Nizar Bhulani, MD, MPH; Elzerie C. de Jager, MBBS (Hons); Stuart Lipsitz, ScD; Nicollette K. Kwon, MSc; Daniel J. Sturgeon, MS; Quoc-Dien Trinh, MD; Tracey Koehlmoos, PhD; Adil H. Haider, MD, MPH; Andrew J. Schoenfeld, MD, MSc
Efficacy of first-line immune checkpoint inhibitors in patients with sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).
Authors: Ziad Bakouny, Sarah Abou Alaiwi, Amin Nassar, John A. Steinharter, Xiao X. Wei, Bradley Alexander McGregor, Lauren Christine Harshman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

66 Background: Patients with mRCC with S/R components tend to have a poor prognosis with few therapeutic options available. Recent data suggest that immune checkpoint inhibitor (ICI)-based therapies may be especially effective for these patients. Our aim was to evaluate the efficacy of ICI-based therapies in patients with S/R mRCC. Methods: We retrospectively assessed objective response rate (ORR), progression free survival (PFS) &amp; overall survival (OS) of patients with S/R mRCC treated at our institution with first-line ICI-based therapies and compared these to those of patients treated with first-line non-ICI-based therapies. Univariable and multivariable (adjusted for IMDC group) Cox and logistic regressions were performed. Results: 92 patients (70 S, 9 R, and 13 S&amp;R) patients were included, of which 74 with a clear-cell component. For all patients (regardless of therapy), 74 (80.4%) patients experienced a PFS event (progression or death) and 52 (56.5%) died at 25.3 months (m) median follow-up. Overall median PFS was 5.3 m (95% CI= 3.4–7.2) and 24 m OS rate was 39.5% (27.4–51.7). Out of 78 patients in whom response was evaluable, ORR was 30.8% (20.4–41.2). Patients treated with ICI-based therapies had significantly better ORR, PFS, and OS on multivariable analysis (table). Conclusions: mRCC patients with S/R components have significantly better ORR, PFS, and OS with first-line ICI-based compared to non-ICI-based therapies. These data support the use of ICI-based therapies for patients with S/R mRCC. [Table: see text]
Correction: Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer
Authors: Anna C. Ferrari, Joshi J. Alumkal, Mark N. Stein, Mary-Ellen Taplin, James Babb, Ethan S. Barnett, Alejandro Gomez-Pinillos, Xiaomei Liu, Dirk Moore, Robert DiPaola, Tomasz M. Beer
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), a sentence was missing in the Results section of the Abstract. The error has been corrected in the latest online HTML and PDF versions of the article. The publisher regrets this error.
Patient Receives First Genetically Engineered Phage Treatment
Authors: Jennifer Abbasi
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands
Authors: Blanda Di Luccia, Susan Gilfillan, Marina Cella, Marco Colonna, Stanley Ching-Cheng Huang
Journal: The Journal of Experimental Medicine (2019)

Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of Th17 that require the transcription factor RORγt for development and contribute to the defense against pathogens through IL-22 and IL-17 secretion. Proliferation and effector functions of Th17 require a specific mTOR-dependent metabolic program that utilizes high-rate glycolysis, while mitochondrial lipid oxidation and production of reactive oxygen species (mROS) support alternative T reg cell differentiation. Whether ILC3s employ a specific metabolic program is not known. Here, we find that ILC3s rely on mTOR complex 1 (mTORC1) for proliferation and production of IL-22 and IL-17A after in vitro activation and Citrobacter rodentium infection. mTORC1 induces activation of HIF1α, which reprograms ILC3 metabolism toward glycolysis and sustained expression of RORγt. However, in contrast to Th17, ILC3 activation requires mROS production; rather than inducing an alternative regulatory fate as it does in CD4 T cells, mROS stabilizes HIF1α and RORγt in ILC3s and thereby promotes their activation. We conclude that ILC3 activation relies on a metabolic program that integrates glycolysis with mROS production.
Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice
Authors: Ronald M. Witteles, Sabahat Bokhari, Thibaud Damy, Perry M. Elliott, Rodney H. Falk, Nowell M. Fine, Mariana Gospodinova, Laura Obici, Claudio Rapezzi, Pablo Garcia-Pavia
Journal: JACC Heart Failure (2019)

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic "red flags" that can assist in its diagnosis among the wider population of patients with heart failure.
New opportunities for targeting redox dysregulation in cardiovascular disease
Authors: Kristen J Bubb, Grant R Drummond, Gemma A Figtree
Journal: Cardiovascular Research (2019)

Despite substantial promise, the use of antioxidant therapy to improve cardiovascular outcomes has been disappointing. Whilst the fundamental biology supporting their use continues to build, the challenge now is to differentially target dysregulated redox signalling domains and to identify new ways to deliver antioxidant substances. Looking further afield to other disciplines, there is an emerging 'tool-kit' containing sophisticated molecular and drug delivery applications. Applying these to the cardiovascular redox field could prove a successful strategy to combat the increasing disease burden. Excessive reactive oxygen species production and protein modifications in the mitochondria has been the target of successful drug development with several positive outcomes emerging in the cardiovascular space, harnessing both improved delivery mechanisms and enhanced understanding of the biological abnormalities. Using this as a blueprint, similar strategies could be applied and expanded upon in other redox-hot-spots, such as the caveolae sub-cellular region, which houses many of the key cardiovascular redox proteins such as NADPH oxidase, endothelial nitric oxide synthase, angiotensin II receptors, and beta adrenoceptors. The expanded tool kit of drug development, including gene and miRNA therapies, nanoparticle technology and micropeptide targeting, can be applied to target dysregulated redox signalling in subcellular compartments of cardiovascular cells. In this review, we consider the opportunities for improving cardiovascular outcomes by utilizing new technology platforms to target subcellular 'bonfires' generated by dysregulated redox pathways, to improve clinical outcomes.
Assessment of treatment patterns in patients with malignant mesothelioma in the United States: A retrospective database analysis.
Authors: Bingcao Wu, Manjiri Pawaskar, Ozgur Tunceli, Tapashi Dalvi, Ramy A. Ibrahim, Fatemeh Tavakkoli, Robert Deeter
Journal: Journal of Clinical Oncology (2013)

e18543 Background: Mesothelioma is a rare malignancy primarily attributed to asbestos exposure and has limited life expectancy. This study examined patient characteristics, and treatment patterns in commercially insured mesothelioma patients in real world setting. Methods: Patients aged ≥18 yrs with mesothelioma diagnosis were identified using ICD-9 and CPT codes/clinical algorithm between 7/1/2006 and 4/30/2011 from HealthCore Integrated Research Database. Patients with other cancers and without continuous insurance enrollment for ≤ 6-mos before or 12-mos post-diagnosis were excluded. Treatments were grouped into surgery, systemic chemotherapy (Ctx), and best supportive care (BSC) and were assessed descriptively. Results: A total of 184 patients were identified (mean age 64 yrs with 41% patients between 45 and 64 yrs old and 48% ≥65 yrs old, 64% males) with diagnosis of mesothelioma. 61% patients had pleural, 25% had peritoneal and 14% had pericardial disease. Only 10% patients received surgery, 27% received Ctx, while 50% received BSC (including radiation). Among patients who received 1 st line Ctx (mean duration 90 days), almost half of patients received pemetrexed based regimen {pemetrexed + cisplatin (18%) or carboplatin (10%) and pemetrexed alone (20%)} followed by carboplatin monotherapy (42%). Among 41% who received 2 nd line Ctx regimens (mean duration 105 days), most commonly used (65%) were pemetrexed based regimens {pemetrexed alone (35%) and pemetrexed + cisplatin (15%) or carboplatin (15%)} followed by single agent gemcitabine (15%). No patients received vinorelbine (0%). In patients who received Ctx, 35% died before receiving 2nd line Ctx and an additional 15% of patients died before receiving 3rd line Ctx. Only 16% received 3 rd line Ctx. Around 41% patients had at least one emergency room visit and 80% had at least one hospitalization. Conclusions: Mesothelioma is predominant in males and older adults in commercially insured patients in the United States. Systemic chemotherapy remains the main treatment strategy with pemetrexed based therapy being most commonly used regimen. This study highlights limited treatment options and high unmet need in this population.
Use of Electronic Cigarettes with Conventional Tobacco Is Associated with Decreased Sleep Quality in Women
Authors: Shreyes A. Boddu, Christine M. Bojanowski, Michael T. Lam, Ira N. Advani, Eric L. Scholten, Xiaoying Sun, Philippe Montgrain, Atul Malhotra, Sonia Jain, Laura E. Crotty Alexander
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
A Call to Accelerate Hidradenitis Suppurativa Research and Improve Care—Moving Beyond Burden
Authors: Haley B. Naik, Michelle A. Lowes
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia–mesenchymal transition during pancreatic carcinogenesis
Authors: Ningning Niu, Ping Lu, Yanlin Yang, Ruizhe He, Li Zhang, Juanjuan Shi, Jinghua Wu, Minwei Yang, Zhi-Gang Zhang, Li-Wei Wang, Wei-Qiang Gao, Aida Habtezion, Gary Guishan Xiao, Yongwei Sun, Li Li, Jing Xue
Journal: Gut (2019)

Objective SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. Design TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice ( Pdx cre Setd2 flox/flox ) together with Kras G12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism. Results SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7 . Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelia–mesenchymal transition (EMT) through impaired epigenetic regulation of Ctnna1 . In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis. Conclusion Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.
PSA Testing Use and Prostate Cancer Diagnostic Stage After the 2012 U.S. Preventive Services Task Force Guideline Changes
Authors: Christopher J. Magnani, Kevin Li, Tina Seto, Kathryn M. McDonald, Douglas W. Blayney, James D. Brooks, Tina Hernandez-Boussard
Journal: Journal of the National Comprehensive Cancer Network (2019)

Most patients with prostate cancer are diagnosed with low-grade, localized disease and may not require definitive treatment. In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate cancer screening to address overdetection and overtreatment. This study sought to determine the effect of guideline changes on prostate-specific antigen (PSA) screening and initial diagnostic stage for prostate cancer.
Pluripotent Stem Cell Heterogeneity: Clonal Isolation of Human Pluripotent Stem Cells on Nanofibrous Substrates Reveals an Advanced Subclone for Cardiomyocyte Differentiation (Adv. Healthcare Mater. 13/2019)
Authors: Leqian Yu, Junjun Li, Itsunari Minami, Xiang Qu, Shigeru Miyagawa, Nanae Fujimoto, Kouichi Hasegawa, Yong Chen, Yoshiki Sawa, Hidetoshi Kotera, Li Liu
Journal: Advanced Healthcare Materials (2019)

In article number 1900165 by Li Liu and co-workers, a nanofibrous platform is used for investigating heterogeneity among single pluripotent stem cells. One type of subclone is established and found to have distinct morphology and its cardiac derivatives show higher differentiation efficiency, increased maturation, and stronger beating compared to those derived from the other subclones. This selection process also holds potential for improving differentiation efficiency toward other cell types.
APC I1307K polymorphism as a predictive factor for colorectal neoplasia recurrence.
Authors: Ben Boursi, Tal Sella, Eliezer Liberman, Ravit Geva, Einat Shmueli, Diana Kazanov, Sarah Kraus, Nadir Arber
Journal: Journal of Clinical Oncology (2013)

1526 Background: The use of surveillance colonoscopy to detect disease recurrence after initial colorectal neoplasia resection has increased significantly in the past decade. Currently, predictive factors at index colonoscopy include only histo-pathologic characteristics such as adenoma number, size, type and dysplasia. The goal of the current study is to identify additional factors (i.e., genetic markers) that increase the risk of subsequent lesions and may optimize the use of surveillance colonoscopies. Methods: A prospective analysis of 383 consecutive Israeli subjects with an initial neoplastic finding in screening colonoscopy. The participants were followed over a period of 10 years, and underwent up to five surveillance colonoscopies. Clinical data regarding potential risk factors for colorectal cancer as well as blood samples were collected. Genetic polymorphisms were detected using real-time PCR from DNA extracted from peripheral mononuclear cells. Results: The overall prevalence of recurrent Colorectal carcinoma and adenoma was 9.4% (36/383) and 69% (268/383) respectively, with a median of 4.8 years from index colonoscopy. In a univariate analysis, subjects with recurrent lesions had significantly higher number of adenomas at index colonoscopy (3.9 Vs 1.1, p=0.001), increased rate of high grade dysplasia (65.8% Vs 50%, p=0.018), and a non-significant trend for larger adenomas and villous histology. The APC I1307K gene variant was detected in 11.8% of subjects with recurrent lesions compared to 3.8% of subjects with normal follow-up colonoscopies (p=0.03). In a multivariate logistic regression (adjusted to age, sex, family history of CR neoplasia, time to recurrence and number of colonoscopies performed), the I1307K variant and the presence of dysplasia were the only significant predictive factors for recurrent neoplasia with an OR of 3.27 (1-11.02, p=0.05) and 1.72 (1.02-2.89, p=0.04) respectively. Conclusions: The APC I1307K gene variant is an important predictive factor for recurrent colorectal neoplasia after a positive index colonoscopy and should be considered as part of the criteria for high risk subjects among Israeli Jews.