tbuckley/cabot-search huggingface dataset:
Liraglutide Improves Myocardial Perfusion and Energetics and Exercise Tolerance in Patients With Type 2 Diabetes
Authors: Amrit Chowdhary, Sharmaine Thirunavukarasu, Tobin Joseph, Nicholas Jex, Sindhoora Kotha, Marilena Giannoudi, Henry Procter, Lizette Cash, Sevval Akkaya, David Broadbent, Hui Xue, Peter Swoboda, Ladislav Valkovič, Peter Kellman, Sven Plein, Oliver J. Rider, Stefan Neubauer, John P. Greenwood, Eylem Levelt
Journal: Journal of the American College of Cardiology (2024)

Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m2) [95% CI: 26.1-29.5 kg/m2)]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009). Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939).
Pericardial Diseases and Best Practices for Pericardiectomy
Authors: Mohamed Al-Kazaz, Allan L. Klein, Jae K. Oh, Juan A. Crestanello, Paul C. Cremer, Michael Z. Tong, Marijan Koprivanac, Valentin Fuster, Ismail El-Hamamsy, David H. Adams, Douglas R. Johnston
Journal: Journal of the American College of Cardiology (2024)
Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’
Authors: Harsh Vardhan Tevethia, Apurva Pande, Rajan Vijayaraghavan, Guresh Kumar, Shiv Kumar Sarin
Journal: Gut (2024)

Objectives Beta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk varices is not clear. A comparison of these therapies alone or in combination to prevent the first variceal bleed in advanced cirrhosis patients was carried out. Design 330 Child-Turcotte-Pugh (CTP) B and C cirrhosis patients, with ‘high-risk’ varices were prospectively enrolled (n=110 per group) to receive carvedilol (group A), VBL (group B) or combination (group C). Primary endpoint was reduction in the incidence of first variceal bleed at 12 months. The secondary endpoints included overall mortality, bleed-related mortality, new-onset decompensation, change in hepatic vein pressure gradient (HVPG) and treatment-related adverse events. Results The patients were predominantly males (85.2%), aged 51.4±10.5 years with CTP score of 8.87±1.24, MELD score 15.17±3.35 and HVPG-16.96±3.57 mm Hg. The overall incidence of variceal bleed was 23.8% (n=78) at 1 year. Intention-to-treat analysis showed that the combination arm (group C) significantly reduced the incidence of first variceal bleed by 62.9% as compared with group B (HR 0.37, 95% CI 0.192 to 0.716, p&lt;0.003) and by 69.3% as compared with group A (HR 0.31, 95% CI 0.163 to 0.578, &lt;0.001). The overall mortality was 13.6% (45/330). The 1-year mortality in group C was lowest among the three groups (A, B, C=20%, 14.5%, 6.3%, p=0.012). Reduction in HVPG (20.8% vs 25.1%, p=0.54) and the rate of non-response to carvedilol (53.4% vs 41.25%, p=0.154) were not different between group A and C patients. The incidence of new-onset ascites, spontaneous bacterial peritonitis, shock, and acute kidney injury and postbleed organ failure was also comparable between the groups. Conclusion In CTP B and C cirrhosis patients with high-risk varices, combination of carvedilol and VBL is more effective than either therapy alone, for primary prevention of variceal bleeding. Trial registration number NCT03069339 .
Femoroacetabular impingement syndrome in middle-aged individuals is strongly associated with the development of hip osteoarthritis within 10-year follow-up: a prospective cohort study (CHECK)
Authors: Rintje Agricola, Michiel M A van Buuren, Joanne L Kemp, Harrie Weinans, Jos Runhaar, Sita M A Bierma-Zeinstra
Journal: British Journal of Sports Medicine (2024)

Objective The objective is to determine the association and absolute risk of femoroacetabular impingement syndrome (FAIS) for the development of radiographic hip osteoarthritis (RHOA). Methods This is a nationwide, multicentre prospective cohort study (Cohort Hip and Cohort Knee) with 1002 individuals aged between 45 and 65 years. Hips without definitive RHOA (Kellgren-Lawrence (KL) grade≤1) at baseline and with anteroposterior pelvic radiographs at baseline and 10-year follow-up available (n=1386 hips) were included. FAIS was defined by the baseline presence of a painful hip, limited internal hip rotation≤25° and cam morphology defined by an alpha angle&gt;60°. The outcomes were incident RHOA (KL grade≥2 or total hip replacement (THR)) and incident end-stage RHOA (KL≥3 or THR) within 10 years. Results Of the 1386 included hips (80% women; mean age 55.7±5.2 years), 21 hips fulfilled criteria for FAIS and 563 hips did not fulfil any of the FAIS criteria (reference group; no symptoms, no signs, no cam morphology). Within 10-year follow-up, 221 hips (38%) developed incident RHOA and 15 hips (3%) developed end-stage RHOA (including 9 hips with THR). Adjusted for sex, age and body mass index, FAIS with cam morphology resulted in an OR of 6.85 (95% CI 2.10 to 22.35) for incident RHOA and 47.82 (95% CI 12.51 to 182.76) for incident end-stage RHOA, compared with hips not having any FAIS criteria. The absolute risk of FAIS was 81% for incident RHOA and 33% for incident end-stage RHOA. Conclusion FAIS was strongly associated with the development of RHOA within 10 years. Although the baseline prevalence of FAIS was low, the high absolute risk of FAIS for RHOA warrants further studies to determine preventive strategies.
Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies
Authors: Atish Mohanty, Michelle Afkhami, Amanda Reyes, Rebecca Pharaon, Holly Yin, Haiqing Li, Dana Do, Diana Bell, Arin Nam, Sue Chang, Thomas Gernon, Robert Kang, Arya Amini, Sagus Sampath, Prakash Kulkarni, Raju Pillai, Vicky Villaflor, Ravi Salgia, Ellie Maghami, Erminia Massarelli
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The study summarizes the potential use of immunotherapy for BRAF- mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database. Materials and methods PTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile. Immunohistochemistry was used to determine the expression of immune suppressive genes and lymphocytic infiltration into the tumor tissue. Thyroid cancer cell lines (MDA-T32, MDA-T68, MDA-T85, and MDA-T120) were used to determine the correlation between the BRAF inhibition and CD274 expression. Results The study found that PTC cases with BRAF mutations had higher expression of immune checkpoint markers CD274 and CTLA4, as well as higher tumor-infiltrating lymphocytes, particularly CD4+T cells. Additionally, the study identified immunosuppressive markers expressed by tumor cells like CD73, CD276, and CD200 that could be targeted for immunotherapy. Further experiments using PTC cell lines lead to the conclusion that CD274 expression correlates with BRAF activity and that inhibitors of BRAF could potentially be used in combination with immunotherapy to treat PTC. Conclusions These findings suggest that PTC cases with BRAF mutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.
Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study
Authors: Niels A.D. Guchelaar, Bo J. Noordman, Marion W. Welten, Myron T. van Santen, Micha J. de Neijs, Stijn L.W. Koolen, Rob H.A. Verhoeven, Esther Oomen-de Hoop, Pieter C. van der Sluis, Sjoerd M. Lagarde, Hanneke W.M. van Laarhoven, Ignace H.J.T. de Hingh, Geert-Jan Creemers, Bianca Mostert, Bas P.L. Wijnhoven, Ron H.J. Mathijssen
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting. Methods: Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics. Results: In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52–0.91, and HR, 0.68; 95% CI, 0.51–0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53–2.83). Conclusions: There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.
General Capillary Endothelial Cells Undergo Reprogramming Into Arterial Endothelial Cells in Pulmonary Hypertension Through HIF-2α/Notch4 Pathway
Authors: Bin Liu, Dan Yi, Xiaomei Xia, Karina Ramirez, Hanqiu Zhao, Yanhong Cao, Ankit Tripathi, Ryan Dong, Anton Gao, Hongxu Ding, Shenfeng Qiu, Vladimir V. Kalinichenko, You-Yang Zhao, Michael B. Fallon, Zhiyu Dai
Journal: Circulation (2024)
Increasing Colorectal Screening Uptake in Spouses of Patients With Colorectal Cancer Using a Randomized Behavioral Trial
Authors: Jerrald Lau, Lina Choe, Daphne Hui Juan Lee, Athena Ming-Gui Khoo, Wei-Ling Koh, Cherie Peh, Alyssa Ng, Tian-Zhi Lim, Bettina Lieske, Kuok-Chung Lee, Choon-Seng Chong, Choon-Sheong Seow, Christopher H.L. Keh, Jing-Yu Ng, Ker-Kan Tan
Journal: Journal of the National Comprehensive Cancer Network (2024)

Colorectal cancer (CRC) is one of the few cancers for which screening has been associated with better survival and morbidity, but screening uptake has been underexplored in spouses of existing patients with CRC. The objective of this study was to evaluate whether a brief, structured behavioral intervention delivered to spouses of patients with CRC in a colorectal clinical setting could increase fecal immunochemical test (FIT) uptake within 3 months of the study period.
Single-Ancestry versus Multi-Ancestry Polygenic Risk Scores for CKD in Black American Populations
Authors: Alana C. Jones, Amit Patki, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Nicole D. Armstrong, Ninad S. Chaudhary, Nita A. Limdi, Bertha A. Hidalgo, Brittney Davis, James J. Cimino, Atlas Khan, Krzysztof Kiryluk, Leslie A. Lange, Ethan M. Lange, Donna K. Arnett, Bessie A. Young, Clarissa J. Diamantidis, Nora Franceschini, Sylvia Wassertheil-Smoller, Stephen S. Rich, Jerome I. Rotter, Josyf C. Mychaleckyj, Holly J. Kramer, Yii-Der I. Chen, Bruce M. Psaty, Jennifer A. Brody, Ian H. de Boer, Nisha Bansal, Joshua C. Bis, Marguerite R. Irvin
Journal: Journal of the American Society of Nephrology (2024)

Key Points The predictive performance of an African ancestry–specific polygenic risk score (PRS) was comparable to a European ancestry–derived PRS for kidney traits. However, multi-ancestry PRSs outperform single-ancestry PRSs in Black American populations. Predictive accuracy of PRSs for CKD was improved with the use of race-free eGFR. Background CKD is a risk factor of cardiovascular disease and early death. Recently, polygenic risk scores (PRSs) have been developed to quantify risk for CKD. However, African ancestry populations are underrepresented in both CKD genetic studies and PRS development overall. Moreover, European ancestry–derived PRSs demonstrate diminished predictive performance in African ancestry populations. Methods This study aimed to develop a PRS for CKD in Black American populations. We obtained score weights from a meta-analysis of genome-wide association studies for eGFR in the Million Veteran Program and Reasons for Geographic and Racial Differences in Stroke Study to develop an eGFR PRS. We optimized the PRS risk model in a cohort of participants from the Hypertension Genetic Epidemiology Network. Validation was performed in subsets of Black participants of the Trans-Omics in Precision Medicine Consortium and Genetics of Hypertension Associated Treatment Study. Results The prevalence of CKD—defined as stage 3 or higher—was associated with the PRS as a continuous predictor (odds ratio [95% confidence interval]: 1.35 [1.08 to 1.68]) and in a threshold-dependent manner. Furthermore, including APOL1 risk status—a putative variant for CKD with higher prevalence among those of sub-Saharan African descent—improved the score's accuracy. PRS associations were robust to sensitivity analyses accounting for traditional CKD risk factors, as well as CKD classification based on prior eGFR equations. Compared with previously published PRS, the predictive performance of our PRS was comparable with a European ancestry–derived PRS for kidney traits. However, single-ancestry PRSs were less predictive than multi-ancestry–derived PRSs. Conclusions In this study, we developed a PRS that was significantly associated with CKD with improved predictive accuracy when including APOL1 risk status. However, PRS generated from multi-ancestry populations outperformed single-ancestry PRS in our study.
A systematic review and meta-ethnography of client and therapist perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences
Authors: Charlotte Huggett, Sarah Peters, Patricia Gooding, Natalie Berry, Daniel Pratt
Journal: Clinical Psychology Review (2024)

This review aimed to develop a conceptual model of the therapeutic alliance in the context of psychotherapy and suicidal experiences from therapist and client perspectives. The protocol was pre-registered on PROSPERO (CRD42021268273). MEDLINE, PsycINFO, Web of Science, Embase and CINAHL were systematically searched from database inception to April 2024. Eligible studies were peer-reviewed, qualitative, and included client and/or therapist's perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences. Studies were critically appraised and analysed using a meta-ethnography approach involving a reciprocal translation of studies and line of argument synthesis. Thirty-seven papers were included, generating two overarching themes; 'Working on the edge' and 'Being ready, willing, and able to build an alliance in the context of suicidal experiences'. Therapeutic alliance in the context of suicidal experiences is unique, fluid, potentially lifesaving, and influenced by multiple inter-connected internal and external processes and systems. Clinical implications emphasise the need to improve training, supervision, and support for therapists to equip them with the additional skills required in navigating the intricacies of the therapeutic alliance with clients who have suicidal experiences. Flexibly interweaving risk assessment into therapeutic conversation was beneficial to the alliance with suicidal clients and enhanced their safety.
Vancomycin-Associated Drug induced Hypersensitivity Syndrome: A Retrospective Cohort Study
Authors: Rachel L Ziebart, Hannah Haberecht, Mark D Davis, David A Wetter, Julio C Sartori-Valinotti, Hafsa M Cantwell, Marian T McEvoy, Nessa Aghazadeh Mohandesi, Olivia C Iverson, Austin Todd, Elizabeth Phillips, Afsaneh Alavi
Journal: Journal of the American Academy of Dermatology (2024)
Author Correction: Genetic and epigenetic influences on the loss of tolerance in autoimmunity
Authors: Peng Zhang, Qianjin Lu
Journal: Cellular and Molecular Immunology (2024)

In the caption of Fig. 1a, the sentence "In the thymus, both highaffinity T and B cells undergo apoptosis."was corrected as follows: "In the thymus, T cells with high affinity for self-antigens undergo apoptosis, while B cells undergo a similar process in the bone marrow."The original article has been corrected.
Non-specific lipid-transfer proteins trigger TLR2 and NOD2 signaling and undergo ligand-dependent endocytosis in epithelial cells
Authors: Nicola Cavallari, Alexander Johnson, Christoph Nagl, Saskia Seiser, Gerald N. Rechberger, Thomas Züllig, Thomas A. Kufer, Adelheid Elbe-Bürger, Sabine Geiselhart, Karin Hoffmann-Sommergruber
Journal: Journal of Allergy and Clinical Immunology (2024)
Advancing Health Disparities Science Through Social Epigenomics Research
Authors: Arielle S. Gillman, Eliseo J. Pérez-Stable, Rina Das
Journal: JAMA Network Open (2024)

Importance Although scientific and technological discoveries have improved the health of the US population overall, racial and ethnic minority (American Indian and Alaska Native, Asian, Black or African American, Hispanic or Latino, or Native Hawaiian and Pacific Islander persons) and socioeconomically disadvantaged populations continue to experience a disproportionate burden of disease and other adverse health conditions. To better understand and address the drivers of health disparities and inform the development of effective interventions, integrative mechanistic studies examining the dynamic interplay of multiple factors across the life course and even between generations are needed. The emerging field of social epigenomics, which seeks to link social stressors and protective factors to health status through the examination of epigenomic modifications of various biological pathways, is one promising area of research contributing to this need. Observations This thematic issue of JAMA Network Open highlights new findings from the grantees of the National Institutes of Health (NIH) Social Epigenomics Program. These findings, taken together, examine the associations of a variety of social, behavioral, and structural factors throughout the life course with epigenomic and other biological changes among populations experiencing health disparities. The studies link early-life exposures, structural inequities, and behavioral factors and interventions to epigenetic changes, and in some studies, later health outcomes. While there is still more work to be done to fully characterize the mechanistic pathways linking social exposures to epigenetic changes and health outcomes, the body of work presented in this special issue represents solid progress toward this goal. Conclusions and Relevance The studies highlighted in this special issue demonstrate important scientific progress in the complex integration of social determinants of health and health disparities with biological pathways and health outcomes to improve understanding of the mechanisms underlying health disparities among various underserved populations. Continued progress remains important in integrating different disciplines to transform the field of health disparities research.