tbuckley/cabot-search huggingface dataset:
Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction
Authors: Senthil Selvaraj, Shachi Patel, Andrew J. Sauer, Robert W. McGarrah, Philip Jones, Lydia Coulter Kwee, Sheryl L. Windsor, Olga Ilkayeva, Michael J. Muehlbauer, Christopher B. Newgard, Barry A. Borlaug, Dalane W. Kitzman, Sanjiv J. Shah, Svati H. Shah, Mikhail N. Kosiborod
Journal: JACC Heart Failure (2024)

Although sodium glucose co-transporter 2 inhibitors (SGLT2is) improve heart failure (HF)-related symptoms and outcomes in HF with preserved ejection fraction (HFpEF), underlying mechanisms remain unclear. In HF with reduced EF, dapagliflozin altered ketone and fatty acid metabolites vs placebo; however, metabolite signatures of SGLT2is have not been well elucidated in HFpEF. The goal of this study was to assess whether SGLT2i treatment altered systemic metabolic pathways and their relationship to outcomes in HFpEF. Targeted profiling of 64 metabolites was performed from 293 participants in PRESERVED-HF (Dapagliflozin in PRESERVED Ejection Fraction Heart Failure), a 12-week, placebo-controlled trial of dapagliflozin. Linear regression assessed changes in metabolite factors defined by principal components analysis (PCA) with dapagliflozin vs placebo. The relationship between changes in metabolite factors with changes in study endpoints was also assessed. The mean age was 70 ± 11 years, 58% were female, and 29% were Black. There were no significant differences in 12 PCA-derived metabolite factors between treatment arms, including metabolites reflecting ketone, fatty acid, or branched-chain amino acid (BCAA) pathways. Combining treatment arms, changes in BCAAs and branched-chain ketoacids were negatively associated with changes in N-terminal pro–B-type natriuretic peptide; changes in medium-/long-chain acylcarnitines were positively associated with changes in N-terminal pro–B-type natriuretic peptide and negatively associated with changes in 6-minute walk test distance; and changes in ketones were negatively associated with changes in weight, without treatment interaction. Leveraging targeted metabolomics in a placebo-controlled SGLT2i trial of HFpEF, dapagliflozin did not alter systemic metabolic as reflected by circulating metabolites, in contrast with reported effects in HF with reduced ejection fraction. Metabolite biomarkers reflecting BCAA, ketone, and fatty acid metabolism were associated with markers of disease severity, suggesting a role for potential novel treatment targets. (Dapagliflozin in PRESERVED Ejection Fraction Heart Failure [PRESERVED-HF]; NCT03030235)
Mitral Regurgitation in Obstructive Hypertrophic Cardiomyopathy
Authors: Paul C. Cremer, Jeffrey B. Geske, Anjali Owens, Wael A. Jaber, Serge C. Harb, Sara Saberi, Andrew Wang, Mark Sherrid, Srihari S. Naidu, Hartzell V. Schaff, Nicholas G. Smedira, Qiuqing Wang, Kathy Wolski, Kathy L. Lampl, Amy J. Sehnert, Steven E. Nissen, Milind Y. Desai
Journal: JACC. Cardiovascular imaging (2024)
Impact of Insurance Status and Region on Angiotensin Receptor–Neprilysin Inhibitor Prescription During Heart Failure Hospitalizations
Authors: Giovanni Davogustto, Quinn S. Wells, Frank E. Harrell, Stephen J. Greene, Dan M. Roden, Lynne W. Stevenson
Journal: JACC Heart Failure (2024)

An angiotensin receptor–neprilysin inhibitor (ARNI) is the preferred renin-angiotensin system (RAS) inhibitor for heart failure with reduced ejection fraction (HFrEF). Among eligible patients, insurance status and prescriber concern regarding out-of-pocket costs may constrain early initiation of ARNI and other new therapies. In this study, the authors sought to evaluate the association of insurance and other social determinants of health with ARNI initiation at discharge from HFrEF hospitalization. The authors analyzed ARNI initiation from January 2017 to June 2020 among patients with HFrEF eligible to receive RAS inhibitor at discharge from hospitals in the Get With The Guidelines–Heart Failure registry. The primary outcome was the proportion of ARNI prescription at discharge among those prescribed RAS inhibitor who were not on ARNI on admission. A logistic regression model was used to determine the association of insurance status, U.S. region, and their interaction, as well as self-reported race, with ARNI initiation at discharge. From 42,766 admissions, 24,904 were excluded for absolute or relative contraindications to RAS inhibitors. RAS inhibitors were prescribed for 16,817 (94.2%) of remaining discharges, for which ARNI was prescribed in 1,640 (9.8%). Self-reported Black patients were less likely to be initiated on ARNI compared to self-reported White patients (OR: 0.64; 95% CI: 0.50-0.81). Compared to Medicare beneficiaries, patients with third-party insurance, Medicaid, or no insurance were less likely to be initiated on ARNI (OR: 0.47 [95% CI: 0.31-0.72], OR: 0.41 [95% CI: 0.25-0.67], and OR: 0.20 [95% CI: 0.08-0.47], respectively). ARNI therapy varied by hospital region, with lowest utilization in the Mountain region. An interaction was demonstrated between the impact of insurance disparities and hospital region. Among patients hospitalized between 2017 and 2020 for HFrEF who were prescribed RAS inhibitor therapy at discharge, insurance status, geographic region, and self-reported race were associated with ARNI initiation.
Myocardial Extracellular Volume Fraction Varies With Hemodynamic Load and After Pulmonary Valve Replacement in TOF
Authors: Ayako Ishikita, Gauri R. Karur, Kate Hanneman, Darren A. Yuen, Rajiv R. Chaturvedi, Mark K. Friedberg, Slava Epelman, Xiaolin He, S. Lucy Roche, Rachel M. Wald
Journal: JACC. Cardiovascular imaging (2024)
Lung transplant donors: barriers and ethical considerations
Authors: None The Lancet Respiratory Medicine
Journal: The Lancet Respiratory Medicine (2024)

Last week the ISHLT meeting was held in Prague, Czech Republic, where experts reported on the latest advances in lung transplantation. Findings from the use of robotically assisted surgery for single-lung transplantation were reported from an expert centre in Spain, a procedure where the incision size is reduced thereby decreasing the amount of discomfort, and potentially improving a patient's recovery time.
Prevalence of multimorbidity in people with and without severe mental illness: a systematic review and meta-analysis
Authors: Sean Halstead, Chester Cao, Grímur Høgnason Mohr, Bjørn H Ebdrup, Toby Pillinger, Robert A McCutcheon, Joseph Firth, Dan Siskind, Nicola Warren
Journal: The Lancet Psychiatry (2024)
The association between academic achievement goals and adolescent depressive symptoms: a prospective cohort study in Australia
Authors: Thomas Steare, Glyn Lewis, Katherine Lange, Gemma Lewis
Journal: The Lancet Child & Adolescent Health (2024)

BackgroundStudents define academic competence across two axes: developing skills and understanding (mastery) versus comparisons with peers (performance), and achieving goals (approach) versus avoiding failure (avoidance). We aimed to examine the longitudinal association between achievement goals and adolescent depressive symptoms.MethodsWe analysed data from the Kindergarten (recruited at age 4–5 years; born between March, 1999, and February, 2000; recruited from March, 2004 to November, 2004) and Baby (recruited at age 0–1 years; born between March, 2003, and February, 2004; recruited from March, 2004 to January, 2005) cohorts of the Longitudinal Study of Australian Children. Participants were identified through the Medicare enrolment database and sampled using a randomised selection stratified by postcode to represent the Australian population. Achievement goals were measured at age 12–13 years with the Achievement Goal Questionnaire (ranges from 1 to 7 on each of the four subscales), and depressive symptoms with the Short Mood and Feelings Questionnaire (score ranges from 0 to 26, with higher scores indicating more severe symptoms) at ages 14–15 years (both cohorts) and 16–17 years (Kindergarten cohort only). Analyses were linear multilevel and traditional regressions, with confounder adjustment, for participants with available data on the exposures, confounders, and outcome.FindingsWe included 3200 participants (1585 female and 1615 male) from the Kindergarten cohort and 2671 participants (1310 female and 1361 male) from the Baby cohort. A 1-point increase in mastery-approach goals was associated with decreased depressive symptom severity score (Kindergarten, –0·33 [95% CI –0·52 to –0·15]; Baby, –0·29 [–0·54 to –0·03]), while a 1-point increase in mastery-avoidance goals was associated with increased depressive symptom severity score (Kindergarten, 0·35 [95% CI 0·21 to 0·48]; Baby, 0·44 [0·25 to 0·64]). A 1-point increase in performance-avoidance goals was associated with increased depressive symptom severity score in the Kindergarten cohort but not the Baby cohort (Kindergarten, 0·26 [95% CI 0·11 to 0·41]; Baby, –0·04 [–0·27 to 0·19]). We found little evidence of an association between depressive symptom severity and performance-approach goals.InterpretationDepressive symptoms in adolescents were associated with their achievement goals, which could be targetable risk factors for future trials to investigate whether school-based interventions that aim to enhance factors consistent with mastery goals (ie, learning skills and understanding the subject, rather than assessing competence in comparison to peers) could prevent depression in adolescents.FundingSir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society.
A new protocol for a single-stage combined cardiopulmonary and echocardiography exercise test: a pilot study
Authors: Dan M Dorobantu, Curtis A Wadey, Ben Berryman, Nurul H Amir, Lynsey Forsythe, A Graham Stuart, Guido E Pieles, Craig A Williams
Journal:  (2024)

Abstract Aims The value of cardiopulmonary exercise testing (CPET) and exercise stress echocardiography (ESE) in managing cardiac disease is well known, but no standard CPET–ESE protocol is currently recommended. This pilot study aims to compare feasibility and cardiac function responses between a new high-intensity single-stage combined test (CPET–hiESE) and a standard maximal ESE (smESE). Methods and results After screening and maximal CPET, all volunteers (n = 21) underwent three ESE modalities: (i) based on the gas exchange threshold (hiESE–GET, 40% of peak-GET, 6 min), (ii) based on heart rate (HR) (hiESE–HR, 80% of peak HR, 6 min), and (iii) smESE (85% of predicted peak HR for age, 3 min). Speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI) were measured at each step. There was superior image quality and data completeness for the right ventricle strain for both hiESE modalities compared with smESE (71.4 and 76.2 vs. 42.9%, P = 0.07). Left ventricular STE data completeness was similar for all three conditions. Despite systematically higher HR, work rate and levels of exertion in the smESE compared with hiESE, STE and TDI parameters were not systematically different. Concordance correlation coefficients ranged from 0.56 to 0.88, lowest for strain rate parameters and mean difference from −0.34 to 1.53, highest for TDI measurements. Conclusion The novel CPET–hiESE protocol allowed for better data completeness, at lower levels of exertion compared with smESE, without systematically different cardiac reserve measurements in healthy participants. This single-stage protocol can be individualized to clinical populations, which would provide practical advantages to standard testing.
Environmental pollutants exposure-derived extracellular vesicles: crucial players in respiratory disorders
Authors: Haoran Shen, Rui Zheng, Mulong Du, David C Christiani
Journal: Thorax (2024)

Individual exposure to environmental pollutants, as one of the most influential drivers of respiratory disorders, has received considerable attention due to its preventability and controllability. Considering that the extracellular vesicle (EV) was an emerging intercellular communication medium, recent studies have highlighted the crucial role of environmental pollutants derived EVs (EPE-EVs) in respiratory disorders.
Left atrial and ventricular deformation: alterations and predictive value of echocardiography parameters in end-stage renal disease patients after kidney transplantation
Authors: Abdulhamid Bagheri, Mohammad Khani, Erfan Ghadirzadeh, Amir Moradi, Fariba Bayat, Seyed Pooria Salehi Mashhad Sari, Elham Paraandavaji, Tooba Akbari, Alaa Hamza Hermis
Journal:  (2024)

Abstract Aims End-stage renal disease (ESRD) patients are prone to alterations in cardiac haemodynamics specifically on the left ventricle (LV) and left atrial (LA) functions usually due to factors like uraemia, fluid overload, and inflammation. While studies on LV function in ESRD exist, research on LA function is limited. Successful kidney transplant (KTx) is believed to reverse pathological cardiac remodelling, and monitoring changes in cardiac strain before and after transplantation may guide pre- and post-transplant care. This study has two main objectives: to investigate alterations in LA and LV strain and other echocardiographic parameters after KTx and to identify independent factors predicting impaired strain parameters post-KTx. Methods and results We conducted a prospective cohort study of 49 ESRD patients who underwent KTx. Echocardiography was performed at baseline and at 3 months after KTx. LV end-diastolic volume, LV end-systolic volume, LV end-diastolic diameter, LV ejection fraction (LVEF), E/e′, maximum LA volume index (LAVi), LV global longitudinal strain (LVGLS), and all LA strain values, including booster (LASb), conduit (LAScd), and reservoir (LASr), improved significantly after KTx (P &amp;lt; 0.05). Regarding independent predictors of impaired LA and LV strains, pre-KTx values of LVEF, LAVi, and NT-proBNP were associated with LVGLS impairment after KTx; pre-KTx values of LAVi and LVEF were associated with LASr impairment after KTx. Conclusion The present study provided valuable evidence on the effects of KTx on uraemic cardiomyopathy demonstrated by LA strain and LV strain improvements and indicated pre-KTx LVEF and LAVi as significant independent predictors of LVGLS and LASr impairment after KTx.
The proprotein convertase <i>FURIN</i> is a novel aneurysm predisposition gene impairing TGF-β signalling
Authors: Zongsheng He, Arne S IJpma, Dianne Vreeken, Daphne Heijsman, Karen Rosier, Hence J M Verhagen, Jorg L de Bruin, Hennie T Brüggenwirth, Jolien W Roos-Hesselink, Jos A Bekkers, Danny F E Huylebroeck, Heleen M M van Beusekom, John W M Creemers, Danielle Majoor-Krakauer
Journal: Cardiovascular Research (2024)

Abstract Aims Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signalling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation. Methods and results Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection. FURIN maturation and activity of these variants were decreased in vitro. Patient-derived fibroblasts showed decreased pro-TGF-β processing, phosphorylation of downstream effector SMAD2 and kinases ERK1/2, and steady-state mRNA levels of the TGF-β-responsive ACTA2 gene. In aortic tissue, collagen and fibrillin fibres were affected. One variant (R745Q), observed in 10 unrelated cases, affected TGF-β signalling variably, indicating effect modification by individual genetic backgrounds. Conclusion FURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-β signalling, depending on individual genetic backgrounds.
Isthmin-1 alleviates cardiac ischaemia/reperfusion injury through cGMP-PKG signalling pathway
Authors: Min Hu, Xin Zhang, Can Hu, Zhen-Guo Ma, Sha-Sha Wang, Teng Teng, Xiao-Feng Zeng, Qi-Zhu Tang
Journal: Cardiovascular Research (2024)

Ischaemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization; however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches.
Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma
Authors: Chengcheng Yan, Melissa A. Richard, Christopher J. Gibson, Jianbo He, Alysia Bosworth, David K. Crossman, Purnima Singh, Lindsey Hageman, Rashi Kalra, Saro H. Armenian, Julie Vose, Daniel J. Weisdorf, Benjamin L. Ebert, Yutaka Yasui, Stephen J. Forman, Ravi Bhatia, Smita Bhatia
Journal: Journal of Clinical Oncology (2024)

Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available.
Hidradenitis suppurativa (HS), systemic inflammatory response syndrome and sepsis, sepsis caused by HS: an empty systematic review
Authors: Ibrahim Maghari, Homer Abiad, Tina Griffin, Joerg Albrecht
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Hidradenitis suppurativa (HS), systemic inflammatory response syndrome and sepsis, sepsis caused by HS: an empty systematic review Get access Ibrahim Maghari, Ibrahim Maghari Conceptualization, Formal analysis, Investigation, Resources, Writing - review & editing Department of Medicine, Cook County Health, Chicago, IL Search for other works by this author on: Oxford Academic Google Scholar Homer Abiad, Homer Abiad Methodology, Project administration, Writing - review & editing Divisions of Infectious DiseasesDepartment of Medicine, Rush Medical College, Chicago, IL Search for other works by this author on: Oxford Academic Google Scholar Tina Griffin, Tina Griffin Data curation, Investigation, Methodology, Writing - original draft, Writing - review & editing Library of the Health Sciences, University of Illinois at Chicago, Chicago, IL, USA Search for other works by this author on: Oxford Academic Google Scholar Joerg Albrecht Joerg Albrecht Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Writing - original draft Department of Medicine, Rush Medical College, Chicago, ILDermatology, Department of Medicine, J. H. Stroger Hospital of Cook County, Chicago, IL Correspondence: Joerg Albrecht. Email: jalbrecht@cookcountyhhs.org https://orcid.org/0000-0002-5998-7773 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae095, https://doi.org/10.1093/bjd/ljae095 Published: 18 April 2024 Article history Received: 22 May 2023 Revision received: 27 February 2024 Corrected and typeset: 18 April 2024 Published: 18 April 2024
CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling
Authors: Yuto Naoi, Takao Morinaga, Joji Nagasaki, Ryo Ariyasu, Youki Ueda, Kazuo Yamashita, Wenhao Zhou, Shusuke Kawashima, Katsushige Kawase, Akiko Honobe-Tabuchi, Takehiro Ohnuma, Tatsuyoshi Kawamura, Yoshiyasu Umeda, Yu Kawahara, Yasuhiro Nakamura, Yukiko Kiniwa, Osamu Yamasaki, Satoshi Fukushima, Masahito Kawazu, Yutaka Suzuki, Hiroyoshi Nishikawa, Toyoyuki Hanazawa, Mizuo Ando, Takashi Inozume, Yosuke Togashi
Journal: Cancer Research (2024)

T-cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T-cell exhaustion, such as programmed death 1, can reinvigorate tumor-specific T cells and activate antitumor immunity in various types of cancer. In this study, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed antitumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to programmed death 1 blockade. Mechanistically, CD106 inhibited T-cell receptor (TCR) signaling by interacting with the TCR/CD3 complex and reducing its surface expression. Together, these findings provide insights into the immunosuppressive role of CD106 expressed in tumor-specific exhausted CD8+ T cells, identifying it as a potential biomarker and therapeutic target for cancer immunotherapy. Significance: CD106 is specifically expressed in tumor-specific exhausted CD8+ T cells and inhibits the TCR signaling pathway by reducing surface expression of the TCR/CD3 complex to suppress antitumor immunity.
Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
Authors: Jacob C.M. Low, Jianbo Cao, Friederike Hesse, Alan J. Wright, Anastasia Tsyben, Islam Alshamleh, Richard Mair, Kevin M. Brindle
Journal: Cancer Research (2024)

Abstract Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. In this study, we used 2H magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging (MRSI) measurements of [6,6′-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived GBM xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial tricarboxylic acid cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6′-2H2]glucose, which are markers of glycolytic activity. Two cell lines representative of a glycolytic subtype and two representative of a mitochondrial subtype were identified. 2H magnetic resonance spectroscopy and MRSI measurements showed similar concentrations of 2H-labeled glucose from [6,6′-2H2]glucose in all four tumor models when implanted orthotopically in mice. The glycolytic subtypes showed higher concentrations of 2H-labeled lactate than the mitochondrial subtypes and normal-appearing brain tissue, whereas the mitochondrial subtypes showed more glutamate/glutamine labeling, a surrogate for tricarboxylic acid cycle activity, than the glycolytic subtypes and normal-appearing brain tissue. The response of the tumors to chemoradiation could be detected within 24 hours of treatment completion, with the mitochondrial subtypes showing a decrease in both 2H-labeled glutamate/glutamine and lactate concentrations and glycolytic tumors showing a decrease in 2H-labeled lactate concentration. This technique has the potential to be used clinically for treatment selection and early detection of treatment response. Significance: Deuterium magnetic resonance spectroscopic imaging of glucose metabolism has the potential to differentiate between glycolytic and mitochondrial metabolic subtypes in glioblastoma and to evaluate early treatment responses, which could guide patient treatment.