tbuckley/cabot-search huggingface dataset:
Dysfunction of estrogen-related receptor alpha-dependent hepatic VLDL secretion contributes to sex disparity in NAFLD/NASH development
Authors: Meng Yang, Qingli Liu, Tongling Huang, Wenjuan Tan, Linbing Qu, Tianke Chen, Haobo Pan, Ling Chen, Jinsong Liu, Chi-Wai Wong, William W Lu, Min Guan
Journal: Theranostics (2020)

Rationale: Men and postmenopausal women are more prone to developing non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) than premenopausal women. However, the pathological links and underlying mechanisms of this disparity are still elusive. The sex-difference in hepatic very low-density lipoprotein (VLDL) assembly and secretion may contribute to NAFLD development. Estrogen-related receptor alpha (ERRα) is a key regulator of several metabolic processes. We hypothesized that ERRα plays a role contributing to the sex-difference in hepatic VLDL assembly and secretion. Methods: VLDL secretion and essential genes governing said process were assessed in male and female mice. Liver-specific ERRα-deficient (ERRαLKO) mice were generated to assess the rate of hepatic VLDL secretion and alteration in target gene expression. Overexpression of either microsomal triglyceride transfer protein (Mttp) or phospholipase A2 G12B (Pla2g12b) by adenovirus was performed to test if the fatty liver phenotype in male ERRαLKO mice was due to defects in hepatic VLDL secretion. Female ERRαLKO mice were put on a diet high in saturated fat, fructose and cholesterol (HFHC) to promote NASH development. Wild type female mice were either ovariectomized or treated with tamoxifen to induce a state of estrogen deficiency or disruption in estrogen signaling. Adenovirus was used to overexpress ERRα in these mice to test if ERRα was sufficient to rescue the suppressed VLDL secretion due to estrogen dysfunction. Finally, wild type male mice on a high-fat diet (HFD) were treated with an ERRα inverse agonist to assess if suppressing ERRα activity pharmacologically would lead to fatty liver development. Results: ERRα is an indispensable mediator modulating hepatic triglyceride-rich very low-density lipoprotein (VLDL-TG) assembly and secretion through coordinately controlling target genes apolipoprotein B (Apob), Mttp and Pla2g12b in a sex-different manner. Hepatic VLDL-TG secretion is blunted in ERRαLKO mice, leading to hepatosteatosis which exacerbates endoplasmic reticulum stress and inflammation paving ways for NASH development. Importantly, ERRα acts downstream of estrogen/ERα signaling in contributing to the sex-difference in hepatic VLDL secretion effecting hepatic lipid homeostasis. Conclusions: Our results highlight ERRα as a key mediator which contributes to the sex disparity in NAFLD development, suggesting that selectively restoring ERRα activity in the liver may be a novel strategy for treating NAFLD/NASH.
Abstract 12383: Radiofrequency and Cryoballoon Ablation for Paroxysmal Atrial Fibrillation Produce Similar Durability of Pulmonary Vein Isolation and Effect on AF Burden (The RACE-AF Trial)
Authors: Samuel K Sorensen, Arne Johannessen, Rene Worck, Morten Hansen, Jim Hansen
Journal: Circulation (2019)

Introduction: Recurrent paroxysmal atrial fibrillation (PAF) after catheter ablation is presumably caused by failure to achieve durable pulmonary vein isolation (PVI). The primary methods of PVI ar...
National Trends in Drug Payments for HIV Preexposure Prophylaxis in the United States, 2014 to 2018
Authors: Nathan W. Furukawa, Weiming Zhu, Ya-Lin A. Huang, Ram K. Shrestha, Karen W. Hoover
Journal: Annals of Internal Medicine (2020)

Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown.To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database.Retrospective cohort study.Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions.Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments.Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance.The IQVIA database does not capture every prescription nationwide.Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion.Centers for Disease Control and Prevention.
Multiomics and Machine Learning Accurately Predict Clinical Response to Adalimumab and Etanercept Therapy in Patients With Rheumatoid Arthritis
Authors: Weiyang Tao, Arno N. Concepcion, Marieke Vianen, Anne C. A. Marijnissen, Floris P. G. J. Lafeber, Timothy R. D. J. Radstake, Aridaman Pandit
Journal: Arthritis & Rheumatology (2020)

To predict response to anti-tumor necrosis factor (anti-TNF) prior to treatment in patients with rheumatoid arthritis (RA), and to comprehensively understand the mechanism of how different RA patients respond differently to anti-TNF treatment.Gene expression and/or DNA methylation profiling on peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells obtained from 80 RA patients before they began either adalimumab (ADA) or etanercept (ETN) therapy was studied. After 6 months, treatment response was evaluated according to the European League Against Rheumatism criteria for disease response. Differential expression and methylation analyses were performed to identify the response-associated transcription and epigenetic signatures. Using these signatures, machine learning models were built by random forest algorithm to predict response prior to anti-TNF treatment, and were further validated by a follow-up study.Transcription signatures in ADA and ETN responders were divergent in PBMCs, and this phenomenon was reproduced in monocytes and CD4+ T cells. The genes up-regulated in CD4+ T cells from ADA responders were enriched in the TNF signaling pathway, while very few pathways were differential in monocytes. Differentially methylated positions (DMPs) were strongly hypermethylated in responders to ETN but not to ADA. The machine learning models for the prediction of response to ADA and ETN using differential genes reached an overall accuracy of 85.9% and 79%, respectively. The models using DMPs reached an overall accuracy of 84.7% and 88% for ADA and ETN, respectively. A follow-up study validated the high performance of these models.Our findings indicate that machine learning models based on molecular signatures accurately predict response before ADA and ETN treatment, paving the path toward personalized anti-TNF treatment.
Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101
Authors: Jan Marie de Gooyer, Fortuné M.K. Elekonawo, Desirée L. Bos, Rachel S. van der Post, André Pèlegrin, Bérénice Framery, Françoise Cailler, Alexander L. Vahrmeijer, Johannes H.W. de Wilt, Mark Rijpkema
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen–targeting tracer, [111In]In-DTPA-SGM-101, for pre- and intraoperative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation. Experimental Design: SGM-101 was conjugated with p-isothiocyanatobenzyl–diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (111In). The biodistribution of 3, 10, 30, and 100 μg [111In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image–guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals. Results: The optimal protein dose of [111In]In-DTPA-SGM-101 was 30 μg (tumor-to-blood ratio, 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 ± 1.0). In mice with intraperitoneal tumors, [111In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image–guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P &amp;lt; 0.001). Conclusions: [111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image–guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image–guided resection of colorectal cancer.
Potential Adverse Financial Implications of the Merit-based Incentive Payment System for Independent and Safety Net Practices
Authors: Carrie H. Colla, Toyin Ajayi, Asaf Bitton
Journal: JAMA (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 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
Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts
Authors: Peter Valent, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Wolfgang R. Sperr, Luis Escribano, Tracy I. George, Hanneke C. Kluin-Nelemans, Celalettin Ustun, Massimo Triggiani, Knut Brockow, Jason Gotlib, Alberto Orfao, Petri T. Kovanen, Emir Hadzijusufovic, Irina Sadovnik, Hans-Peter Horny, Michel Arock, Lawrence B. Schwartz, K. Frank Austen, Dean D. Metcalfe, Stephen J. Galli
Journal: Theranostics (2020)

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879.MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases.However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years.MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs.In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings.The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells.The clinical consequences of the expansion and/or activation of MCs are best IvyspringInternational Publisher established in mastocytosis and in allergic inflammation.However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes.In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease.We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs.
Inclusion Across the Lifespan in Cardiovascular Trials—A Long Road Ahead
Authors: Colette DeJong, Kenneth Covinsky
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Chikungunya Virus–Like Particle Vaccine—Reply
Authors: Grace L. Chen
Journal: JAMA (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 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
RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma
Authors: Lo-Kong Chan, Daniel Wai-Hung Ho, Charles Shing Kam, Elley Yung-Tuen Chiu, Irene Lai-Oi Lo, Derek Tsz-Wai Yau, Elaine Tin-Yan Cheung, Chung-Ngai Tang, Victor Wai-Lun Tang, Terence Kin-Wah Lee, Carmen Chak-Lui Wong, Kenneth Siu-Ho Chok, Albert Chi-Yan Chan, Tan-To Cheung, Chun-Ming Wong, Irene Oi-Lin Ng
Journal: Journal of Hepatology (2020)
Antibiotic-Sparing Gonorrhea Diagnostic Wins Federal Funding
Authors: Jennifer Abbasi
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005–2014
Authors: Catherine R. Butler, Peter P. Reese, James D. Perkins, Yoshio N. Hall, J. Randall Curtis, Manjula Kurella Tamura, Ann M. O'Hare
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement For patients with ESKD, hoping for or receiving a kidney transplant can shape prognostic expectations and care processes. In this manuscript, the authors describe more intensive, inpatient-oriented patterns of end-of-life care for patients with ESKD who had been waitlisted for a kidney transplant or received a transplant, compared with other patients with ESKD. Patients who died while on the transplant waitlist were also less likely to have received hospice services and less likely to have discontinued dialysis before death. Because there are powerful defaults favoring use of aggressive interventions to prolong life in most health systems in the United States, these findings suggest that the broad relevance of advance care planning for patients with ESKD extends to the relatively healthy segment of this population that has engaged in the transplant process. Background The care of patients in the United States who have ESKD is often shaped by their hopes and prognostic expectations related to kidney transplant. Little is known about how patients’ engagement in the transplant process might relate to patterns of end-of-life care. Methods We compared six measures of intensity of end-of-life care among adults in the United States with ESKD who died between 2005 and 2014 after experiencing differing exposure to the kidney transplant process. Results Of 567,832 decedents with ESKD, 27,633 (5%) had a functioning kidney transplant at the time of death, 14,653 (3%) had a failed transplant, 16,490 (3%) had been removed from the deceased donor waitlist, 17,010 (3%) were inactive on the waitlist, 11,529 (2%) were active on the waitlist, and 480,517 (85%) had never been waitlisted for or received a transplant (reference group). In adjusted analyses, compared with the reference group, patients exposed to the transplant process were significantly more likely to have been admitted to an intensive care unit and to have received an intensive procedure in the last 30 days of life; they were also significantly more likely to have died in the hospital. Those who died on the transplant waitlist were also less likely than those in the reference group to have been enrolled in hospice and to have discontinued dialysis before death. Conclusions Patients who had engaged in the kidney transplant process received more intensive patterns of end-of-life care than other patients with ESKD. These findings support the relevance of advance care planning, even for this relatively healthy segment of the ESKD population.
Neurological Impairments in a Patient Returning From Cuba
Authors: Yonatan Serlin, Jeffrey Minuk, Ronald Schondorf
Journal: JAMA Neurology (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 Neurology 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 Neurology journal