tbuckley/cabot-search huggingface dataset:
Src homology 3 domain binding kinase 1 protects against hepatic steatosis and insulin resistance through the Nur77–FGF21 pathway
Authors: Palak Ahuja, Xinyi Bi, Chun Fai Ng, Margaret Chui Ling Tse, Miaojia Hang, Brian Pak Shing Pang, Elsie Chit Yu Iu, Wing Suen Chan, Xin Ci Ooi, Anqi Sun, Oana Herlea‐Pana, Zhixue Liu, Xiuying Yang, Baowei Jiao, Xin Ma, Kelvin Ka Lok Wu, Leo Tsz On Lee, Kenneth King Yip Cheng, Chi Wai Lee, Chi Bun Chan
Journal: Hepatology (2022)

Background and Aims: Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity. Approach and Results: Enhanced Sbk1 expression was found in the liver of high‐fat diet (HFD)–induced obese mice and fatty acid (FA)–challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver‐specific SBK1 knockout ( Lsko ) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox ( Fl/Fl ) control mice when fed the HFD. The HFD‐fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high‐fructose diet–induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1 ‐overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism. Conclusions: Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77–FGF21 pathway.
LEFT VENTRICULAR OUTFLOW TRACT MORPHOLOGY AS A PREDICTOR OF CONDUCTION DISTURBANCES AFTER TAVI
Authors: Luis Alfonso Marroquin Donday, Angela Carolina Espejo Paeres, Angela McInerney, Breda Hennessey, María José Pérez Vizcayno, Gabriela Tirado Conte, Fernando Macaya Ten, Iván J. Núñez Gil, Hernán Mejía Rentería, Nieves Gonzalo, Pablo Salinas, Antonio Fernández Ortiz, Javier Escaned, Luis Nombela Franco, Pilar Jiménez Quevedo
Journal: Journal of the American College of Cardiology (2022)
ORSIRO (ULTRATHIN-STRUT, BIODEGRADABLE-POLYMER, SIROLIMUS-ELUTING STENTS) VERSUS THIN-STRUT, DURABLE-POLYMER,EVEROLIMUS-ELUTING STENTS FOR PERCUTANEOUS CORONARY REVASCULARISATION IN THE STEMI POPULATION
Authors: Stephanie Liew, Diem Dinh, Angela L. Brennan, David John Clark, Andrew Edward Ajani, Ernesto Oqueli, Stephen Duffy, Christopher Michael Reid, Melanie Freeman, Andrew Katzer, Adam Hutchison, Catherine Jaworski, Michael Mok, Chin Hiew, Martin Sebastian
Journal: Journal of the American College of Cardiology (2022)
COMPARATIVE ANALYSIS OF PERCUTANEOUS REVASCULARIZATION PRACTICE IN THE UNITED STATES AND THE UNITED KINGDOM: INSIGHTS FROM THE BMC2 AND BCIS DATABASES
Authors: Brett Wanamaker, Ahmad Shoaib, Milan Seth, Devraj Sukul, Mamas A. Mamas, Hitinder S. Gurm
Journal: Journal of the American College of Cardiology (2022)
Involvement of Radiation Oncologists in Multidisciplinary Decision-making for Early-Stage Lung Cancer
Authors: Nils D. Arvold
Journal: JAMA Network Open (2022)

Michael G. Milligan, MD, MBA; Inga T. Lennes, MD, MBA, MPH; Saif Hawari, MBBS; Melin J. Khandekar, MD, PhD; Yolonda Colson, MD, PhD; Jo-Anne O. Shepard, MD; Angela Frank, MD, MPH; Lecia V. Sequist, MD, MPH; Henning Willers, MD; Florence K. Keane, MD
APICAL VARIANT HYPERTROPHIC CARDIOMYOPATHY WITH LEFT VENTRICULAR CAVITY OBSTRUCTION AND APICAL ANEURYSM MIMICKING ACUTE ST-ELEVATION MYOCARDIAL INFARCTION. A VERY RARE PRESENTATION OF A RARE CONDITION.
Authors: Baher AL Abbasi, Alberto A. Sabates, Majd Jazaerly, Carlos Vergara, Andrew S. Krasner, Robert D. Chait
Journal: Journal of the American College of Cardiology (2022)
Effect of a Default Order vs an Alert in the Electronic Health Record on Hepatitis C Virus Screening Among Hospitalized Patients
Authors: Shivan J. Mehta, Jessie Torgersen, Dylan S. Small, Colleen P. Mallozzi, John D. McGreevey, Charles A.L. Rareshide, Chalanda N. Evans, Mika Epps, David Stabile, Christopher K. Snider, Mitesh S. Patel
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Hepatitis C virus (HCV) screening has been recommended for patients born between 1945 and 1965, but rates remain low. <h3>Objective</h3> To evaluate whether a default order within the admission order set increases HCV screening compared with a preexisting alert within the electronic health record. <h3>Design, Setting, and Participants</h3> This stepped-wedge randomized clinical trial was conducted from June 23, 2020, to April 10, 2021, at 2 hospitals within an academic medical center. Hospitalized patients born between 1945 and 1965 with no history of screening were included in the analysis. <h3>Interventions</h3> During wedge 1 (a preintervention period), both hospital sites had an electronic alert prompting clinicians to consider HCV screening. During wedge 2, the first intervention wedge, the hospital site randomized to intervention (hospital B) had a default order for HCV screening implemented within the admission order set. During wedge 3, the second intervention wedge, the hospital site randomized to control (hospital A) had the default order set implemented. <h3>Main Outcomes and Measures</h3> Percentage of eligible patients who received HCV screening during the hospital stay. <h3>Results</h3> The study included 7634 patients (4405 in the control group and 3229 in the intervention group). The mean (SD) age was 65.4 (5.8) years; 4246 patients (55.6%) were men; 2142 (28.1%) were Black and 4625 (60.6%) were White; and 2885 (37.8%) had commercial insurance and 3950 (51.7%) had Medicare. The baseline rate of HCV screening in wedge 1 was 585 of 1560 patients (37.5% [95% CI, 35.1%-40.0%]) in hospital A and 309 of 1003 patients (30.8% [95% CI, 27.9%-33.7%]) in hospital B. The main adjusted model showed an increase of 31.8 (95% CI, 29.7-33.8) percentage points in test completion in the intervention group compared with the control group (<i>P</i>&lt;. 001). <h3>Conclusions and Relevance</h3> This stepped-wedge randomized clinical trial found that embedding HCV screening as a default order in the electronic health record substantially increased ordering and completion of testing in the hospital compared with a conventional interruptive alert. <h3>Trial Registration</h3> Clinicaltrials.gov:NCT04525690
FEASIBILITY OF A VIRTUAL BLOOD PRESSURE MONITORING PROGRAM TITRATED TO ACC/AHA GUIDELINES AMONG OUTPATIENT POSTPARTUM WOMEN WITH HYPERTENSION: A PILOT STUDY
Authors: Daniela R. Crousillat, Paola Del Cueto, Nandita S. Scott, Jessicca Tangren, Allison Bryant Mantha, Ilona Goldfarb, Amy Sarma
Journal: Journal of the American College of Cardiology (2022)
Patients With Complete Paralysis Walk With Spinal Cord Implant
Authors: Jennifer Abbasi
Journal: JAMA (2022)

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
EARLY EPICARDIAL ACCESS FOR VENTRICULAR TACHYCARDIA ABLATION IN PATIENTS WITH NON ISCHEMIC CARDIOMYOPATHY: A MULTI CENTER ANALYSIS
Authors: Adnan Ahmed, Rishi Ajeet Charate, Jalaj Garg, Naga Venkata K. Pothineni, Sharan Sharma, Mohit Turagam, Ghulam Murtaza, Rakesh Gopinathannair, Dhanunjaya R. Lakkireddy
Journal: Journal of the American College of Cardiology (2022)
Overcoming tumor heterogeneity by ex vivo arming of T cells using multiple bispecific antibodies
Authors: Jeong A Park, Nai-Kong V Cheung
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Tumorous heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-(L)-scFv bispecific antibodies (BsAbs) are potent tumor-specific cytotoxic effectors. To improve the anti-tumor efficacy of EATs against heterogeneous solid tumors, we explored multi-antigen targeting approaches. Methods Ex vivo expanded T cells were armed with BsAbs built on the IgG-(L)-scFv platform, where an anti-CD3 (huOKT3) scFv was attached to the carboxyl end of both light chains of a tumor specific IgG. Multispecificity was created by combining monospecific EATs, combining BsAbs on the same T cell, or combining specificities on the same antibody. Three multi-antigens targeting EAT strategies were tested: (1) pooled-EATs (EATs each with unique specificity administered simultaneously) or alternate-EATs (EATs each with unique specificity administered in an alternating schedule), (2) dual-EATs or multi-EATs (T cells simultaneously armed with ≥2 BsAbs), and (3) TriAb-EATs (T cells armed with BsAb specific for two targets besides CD3 (TriAb)). The properties and efficiencies of these three strategies were evaluated by flow cytometry, in vitro cytotoxicity, cytokine release assays, and in vivo studies performed in BALB- Rag2 -/- IL-2R- γc -KO (BRG) mice xenografted with cancer cell line (CDX) or patient-derived tumor (PDX). Results Multi-EATs retained target antigen specificity and anti-tumor potency. Cytokine release with multi-EATs in the presence of tumor cells was substantially less than when multiple BsAbs were mixed with unarmed T cells. When tested against CDXs or PDXs, dual-EATs or multi-EATs effectively suppressed tumor growth without clinical toxicities. Most importantly, dual-EATs or multi-EATs were highly efficient in preventing clonal escape while mono-EATs or TriAb- EATs were not as effective. Conclusions Multi-EATs have the potential to increase potency, reduce toxicity, and overcome tumor heterogeneity without excessive cytokine release. Arming T cells with multiple BsAbs deserves further exploration to prevent or to treat cancer resistance.
VENTRICULAR ARRHYTHMIAS IN THE SETTING OF A FONTAN CIRCULATION: PREVALENCE, RISK FACTORS AND CLINICAL IMPLICATIONS
Authors: Charis Tan, Diana Zannino, Carley Clendenning, Sophie Offen, Thomas Gentles, Julian Ayer, Mark McGuire, Yves d'Udekem, Rachel Cordina
Journal: Journal of the American College of Cardiology (2022)
Loss of H3K27 Trimethylation Promotes Radiotherapy Resistance in Medulloblastoma and Induces an Actionable Vulnerability to BET Inhibition
Authors: Nishanth Gabriel, Kumaresh Balaji, Kay Jayachandran, Matthew Inkman, Jin Zhang, Sonika Dahiya, Michael Goldstein
Journal: Cancer Research (2022)

Abstract Medulloblastoma has been categorized into four subgroups based on genetic, epigenetic, and transcriptional profiling. Radiation is used for treating medulloblastoma regardless of the subgroup. A better understanding of the molecular pathways determining radiotherapy response could help improve medulloblastoma treatment. Here, we investigated the role of the EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit)-dependent histone H3K27 trimethylation in radiotherapy response in medulloblastoma. The tumors in 47.2% of patients with group 3 and 4 medulloblastoma displayed H3K27me3 deficiency. Loss of H3K27me3 was associated with a radioresistant phenotype, high relapse rates, and poor overall survival. In H3K27me3-deficient medulloblastoma cells, an epigenetic switch from H3K27me3 to H3K27ac occurred at specific genomic loci, altering the transcriptional profile. The resulting upregulation of EPHA2 stimulated excessive activation of the prosurvival AKT signaling pathway, leading to radiotherapy resistance. Bromodomain and extraterminal motif (BET) inhibition overcame radiation resistance in H3K27me3-deficient medulloblastoma cells by suppressing H3K27ac levels, blunting EPHA2 overexpression, and mitigating excessive AKT signaling. In addition, BET inhibition sensitized medulloblastoma cells to radiation by enhancing the apoptotic response through suppression of Bcl-xL and upregulation of Bim. This work demonstrates a novel mechanism of radiation resistance in medulloblastoma and identifies an epigenetic marker predictive of radiotherapy response. On the basis of these findings, we propose an epigenetically guided treatment approach targeting radiotherapy resistance in patients with medulloblastoma. Significance: This study demonstrates a novel epigenetic mechanism of radiation resistance in medulloblastoma and identifies a therapeutic approach to improve outcomes in these patients.
TO TREAT OR NOT TO TREAT SPONTANEOUS CORONARY ARTERY DISSECTION? THAT IS THE QUESTION
Authors: Prateeth Pati, Stephen Sawyer, Marc Iskandar, Allan Julian Beall, Joaquin B. Gonzalez, Pooja Mishra, Mauro Taveras, Megan E. Barber
Journal: Journal of the American College of Cardiology (2022)
INPATIENT HOSPITAL MORTALITY IN SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD)
Authors: Mohsin Mughal, Hafsa Akbar, Hasan Mirza, Weiyi Xia, Ali Ghani, Jagpreet Grewal, Sundeep Kumar, Moaz Ahmad, Muhammad Zahid A. Raza, Muhammad Khakwani, Mahboob Alam, Sergio Waxman, Fahad Waqar, Najam Wasty, Howard L. Levitt, Mohammed Haris Usman
Journal: Journal of the American College of Cardiology (2022)
Highly bioactive iridium metal-complex alleviates spinal cord injury via ROS scavenging and inflammation reduction
Authors: Zhi-Sheng Ji, Gui-Bin Gao, Yan-Ming Ma, Jian-Xian Luo, Guo-Wei Zhang, Hua Yang, Nan Li, Qing-Yu He, Hong-Sheng Lin
Journal: Biomaterials (2022)
CAR T Cells Activate Cancer Therapy
Journal: Cancer Discovery (2022)

CAR T cells modified to produce bacterial enzymes can activate tumor-killing prodrugs. The cells, dubbed SEAKER cells, home in on tumor cells, proliferate, and produce large quantities of the enzymes, which then activate the prodrug. The research demonstrates that CAR T cells' cancer-killing ability can be boosted in vitro and increase survival of mice with tumors.
Drug-induced interstitial lung disease
Authors: Paolo Spagnolo, Philippe Bonniaud, Giulio Rossi, Nicola Sverzellati, Vincent Cottin
Journal: European Respiratory Journal (2022)

Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the development of ILD continues to rise, mainly due to the use of novel monoclonal antibodies and biologicals for neoplastic and rheumatological diseases, and includes, among others, chemotherapeutics, molecular targeting agents, immune checkpoint inhibitors, antibiotics, antiarrhythmics and conventional or biological disease-modifying antirheumatic drugs. Drug-induced ILD (DI-ILD) manifests with a variety of clinical patterns, ranging from mild respiratory symptoms to rapidly progressive respiratory failure and death. In most cases, there are no pathognomonic clinical, laboratory, radiological or pathological features and the diagnosis of DI-ILD is suspected in the presence of exposure to a drug known to cause lung toxicity and after exclusion of alternative causes of ILD. Early identification and permanent discontinuation of the culprit drug are the cornerstones of treatment with systemic glucocorticoids being used in patients with disabling or progressive disease. However, for certain drugs, such as checkpoint inhibitors, the frequency of lung toxicity is such that mitigation strategies are put in place to prevent this complication, and occurrence of DI-ILD is not necessarily synonymous with permanent drug discontinuation, particularly in the absence of valid therapeutic alternatives.
PHYSICIAN PERSPECTIVES ON BETA-BLOCKER USE IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Mahad Musse, Jennifer D. Lau, Brian Yum, Laura C. Pinheiro, Hannah Curtis, Timothy Anderson, Michael Steinman, Markus Meyer, Scott L. Hummel, Parag Goyal
Journal: Journal of the American College of Cardiology (2022)
Vaccination against SARS-CoV-2 infection among vulnerable and marginalised population groups in Denmark: A nationwide population-based study
Authors: Sandra Feodor Nilsson, Thomas Munk Laursen, Merete Osler, Carsten Hjorthøj, Michael E. Benros, Steen Ethelberg, Kåre Mølbak, Merete Nordentoft
Journal: The Lancet Regional Health - Europe (2022)

Social deprivation, psychiatric and medical disorders have been associated with increased risk of infection and severe COVID-19-related health problems. We aimed to study the rates of SARS-CoV-2 vaccination in these high-risk groups.Using health, vaccination, and administrative registers, we performed a population-based cohort study including all Danish residents aged at least 15 years, December 27, 2020, to October 15, 2021. Population groups were people experiencing: (1) homelessness, (2) imprisonment, (3) substance abuse, (4) severe mental illness, (5) supported psychiatric housing, (6) psychiatric admission, and (7) chronic medical condition. The outcome was vaccine uptake of two doses against SARS-CoV-2 infection. We calculated cumulative vaccine uptake and adjusted vaccination incidence rate ratios (IRRs) relative to the general population by sex and population group.The cohort included 4,935,344 individuals, of whom 4,277,380 (86·7%) received two doses of vaccine. Lower cumulative vaccine uptake was found for all socially deprived and psychiatrically vulnerable population groups compared with the general population. Lowest uptake was found for people below 65 years experiencing homelessness (54·6%, 95% confidence interval (CI) 53·4-55·8, p<0·0001). After adjustment for age and calendar time, homelessness was associated with markedly lower rates of vaccine uptake (IRR 0·5, 95% CI 0·5-0·6 in males and 0·4, 0·4-0·5 in females) with similar results for imprisonment. Lower vaccine uptake was also found for most of the psychiatric groups with the lower IRR for substance abuse (IRR 0·7, 0·7-0·7 in males and 0·8, 0·8-0·8 in females). Individuals with new-onset severe mental illness and, especially, those in supported psychiatric housing and with chronic medical conditions had the highest vaccine uptake among the studied population groups.Especially, socially deprived population groups, but also individuals with psychiatric vulnerability need higher priority in the implementation of the vaccination strategy to increase equity in immunization uptake.Novo Nordisk Foundation.
Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study
Authors: Rashidatu Fouad Kamara, Matthew J Saunders, Foday Sahr, Juan E Losa-Garcia, Lynda Foray, Geraint Davies, Tom Wingfield
Journal: The Lancet Global Health (2022)

Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes.This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up).Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes.MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens.Wellcome Trust, Joint Global Health Trials.
Neurons detect cognitive boundaries to structure episodic memories in humans
Authors: Jie Zheng, Andrea G. P. Schjetnan, Mar Yebra, Bernard A. Gomes, Clayton P. Mosher, Suneil K. Kalia, Taufik A. Valiante, Adam N. Mamelak, Gabriel Kreiman, Ueli Rutishauser
Journal: Nature Neuroscience (2022)