bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatigue After Stroke Educational Recovery Program: A Prospective, Phase III, Randomized Controlled Trial
Authors: Jones Kelly , Krishnamurthi Rita , Barker‐Collo Suzanne , De Silva Sulekha , Henry Nathan , Zeng Irene , Vorster Anja , Te Ao Braden , Green Geoff , Ratnasabapathy Yogini , Feigin Valery 
Published: December 2024

Background
Poststroke fatigue affects ≈50% of patients with stroke, causing significant personal, societal, and economic burden. In the FASTER (Fatigue After Stroke Educational Recovery) study, we assessed a group‐based educational intervention for poststroke fatigue.

Methods and Results

Two hundred patients with clinically significant fatigue were included and randomized to either a general stroke education control or fatigue management group (FMG) intervention and assessed at baseline, 6 weeks, and 3 months. The FMG involved weekly psychoeducation sessions over 6 weeks. Coprimary outcomes were the Fatigue Severity Scale and Multidimensional Fatigue Inventory‐20 total scores. Adjusted mean total Fatigue Severity Scale scores at 6 weeks (primary end point) were nearly identical for the education control and FMG groups. The adjusted mean difference between treatment groups was −0.13 (SE, 1.4;
P
=0.92) at 6 weeks and 1.67 (SE, 1.4;
P
=0.26) at 3 months. Although there were no significant effects, Fatigue Severity Scale outcomes were in the direction of a treatment effect based on the estimated change. Adjusted mean total Multidimensional Fatigue Inventory‐20 scores at 6 weeks (primary end point) were similar for the education control and FMG groups. The adjusted mean difference between treatment groups was −0.91 (SE, 1.54;
P
=0.55) at 6 weeks and −1.26 (SE, 1.8;
P
=0.49) at 3 months. Both groups had similar secondary outcomes (eg, Multidimensional Fatigue Inventory‐20 subscales, sleep, pain, mood, quality of life) at 6 weeks and 3 months.

Conclusions
We found no evidence of significant group‐level benefits of FMG over and above general stroke education. Educational group‐based interventions for poststroke fatigue should continue to be refined and examined, including consideration of potential impacts at an individual level.

Registration

URL:
https://www.anzctr.org.au/
; UnIque identifier: ACTRN12619000626167.
Association Between Sleep Duration and Cardiovascular Disease Among Asian Americans
Authors: Nadarajah Santhosh , Akiba Risa , Maricar Isabelle , Vohra Sanah , Jamal Armaan , Yano Yuichiro , Srinivasan Malathi , Kim Gloria , Huang Robert J. , Palaniappan Latha , Kim Karina , Elfassy Tali , Yang Eugene 
Published: December 2024

Background
Cardiovascular disease (CVD) prevalence varies widely among Asian American adults. The American Heart Association added healthy sleep to its metrics to define ideal cardiovascular health. Little is known about the association between sleep and CVD prevalence among Asian subgroups. We aim to examine the association between suboptimal sleep duration and CVD risk prevalence among Asian American subgroups.

Methods and Results
We used 2012 to 2018 National Health Interview Survey data to examine the association between suboptimal sleep duration and CVD prevalence. We included 6868 self‐identifying Asian adults age >40 years (Asian Indian [n=1053], Chinese [n=1415], Filipino [n=1734], and Other Asian [n=2666] adults). Suboptimal sleep was defined as <7 or >9 hours per night. CVD was defined as self‐reported stroke, heart attack, coronary artery disease, or angina. Logistic regression was used to calculate odds ratios and 95% CI to estimate the association between suboptimal sleep duration and CVD prevalence. Filipino and Other Asian participants with suboptimal sleep had the highest prevalence of CVD. Aggregated Asian American participants with suboptimal sleep duration had a higher prevalence of CVD (odds ratio [95% CI, 1.35 [1.09–1.68]) compared with those with optimal sleep duration. After stratification by race or ethnicity or both, a significant association persisted for Other Asian participants (1.77 [95% CI, 1.27–2.46]) but not among all other Asian American subgroups.

Conclusions
Our study highlights the heterogeneity of CVD prevalence associated with suboptimal sleep duration among Asian American adults. Future studies should consider how different measures of sleep duration and quality affect CVD outcomes among disaggregated Asian American subgroups.
Diacylglycerol Kinase ζ Attenuates Doxorubicin‐Induced Cardiotoxicity Through p53 Degradation
Authors: Tachibana Shingo , Otaki Yoichiro , Watanabe Tetsu , Goto Jun , Ochi Haruki , Tanaka Toshiaki , Ono Hiroe , Yamaguchi Ryuhei , Sato Junya , Takahashi Hiroki , Arimoto Takanori , Goto Kaoru , Watanabe Masafumi 
Published: December 2024

Background
Doxorubicin‐induced cardiotoxicity is still an important medical problem associated with a high mortality rate in cancer survivors. p53 plays a key role in doxorubicin‐induced cardiotoxicity. Diacylglycerol kinase ζ (Dgkζ), a 130‐kDa enzyme abundant in cardiomyocytes, regulates the p53 protein expression level in neurons. To elucidate the mechanism of doxorubicin‐induced cardiotoxicity, we focused on the functional role of Dgkζ and its interaction with heat shock protein 70 (Hsp70)–related ubiquitin E3 ligases such as E6‐associated protein (E6ap) and C‐terminus of Hsp70‐interacting protein.

Methods and Results

Protein interactions of Dgkζ with Hsp70 and E6ap were confirmed by immunoprecipitation, but not C‐terminus of Hsp70‐interacting protein. We administered doxorubicin in cardiac‐specific overexpression of Dgkζ transgenic (Dgkζ‐Tg) mice and wild‐type littermates. Dgkζ‐Tg mice showed lower p53 protein expression levels, preserved cardiac function, and improved survival rates compared with wild‐type littermates after doxorubicin administration. RNA sequence analysis of myocardial tissues from Dgkζ‐Tg after doxorubicin stimulation identified
Hspa1b
encoding Hsp70 as the differentially expressed gene. Dgkζ overexpression increased proteasomal p53 degradation and attenuated cardiomyocyte apoptosis after doxorubicin stimulation in cardiomyocytes, which was reversed by knockdown of E6ap. Dgkζ interacted with E6ap through ankyrin‐like repeats. The overexpression of mutant Dgkζ, lacking ankyrin‐like repeats, failed to inhibit p53 protein expression after doxorubicin stimulation. In Dgkζ‐overexpressing cardiomyocytes, expression levels of p53 and caspase‐3 were increased by knockdown of the C‐terminus of Hsp70‐interacting protein.

Conclusions
We demonstrated for the first time that Dgkζ augments p53 ubiquitin‐proteasome degradation and ameliorates doxorubicin‐induced cardiotoxicity by interacting with Hsp70 and E3 ligases such as E6ap and C‐terminus of Hsp70‐interacting protein.
Myocarditis in Patients Starting Combination Checkpoint Inhibitor Therapy: Analysis of a Commercial Claims Database
Authors: Lindsay Alistair C. , Walker Alexander M. , Schneeweiss Sebastian 
Published: December 2024

Background
Immune checkpoint inhibitors have improved the clinical outcomes of several cancers but have also been associated with a greater risk of immune‐related adverse effects, especially when combined. The objective of this study was to investigate the incidence of myocarditis in relation to the use of dual concurrent versus single immune checkpoint inhibitors therapies.

Methods and Results
A cohort study was conducted using medical and pharmacy claims data (2011–2022) from a large US commercial insurer. Cox regression quantified the comparative risks of myocarditis or heart failure in patients with cancer receiving treatment with combination therapy (nivolumab and ipilimumab) in comparison to taking a single immune checkpoint inhibitor only. Mean follow‐up time in 53 018 patients was 226 days (interquartile range, 93–495 days). There were 148 cases of myocarditis (0.3%), 33 (0.7%) in patients on combination therapy, and 115 (0.2%) in patients on monotherapy. The risk of myocarditis per 1000 patients was 7.40 in the combination therapy group and 2.37 in the monotherapy group (risk ratio, 3.12 [95% CI, 2.12–4.60]). Using multivariable regression analysis, the hazard ratio for myocarditis in the combination therapy group was 2.38 (1.57–3.63). No difference in the risk of heart failure was found between combination and single therapy.

Conclusions
Therapy with 2 immune checkpoint inhibitors was associated with an increased risk of myocarditis compared with monotherapy, with most cases occurring in the first 6 months of therapy.
Single Cell Transcriptomic Profiling of
MYBPC3
‐Associated Hypertrophic Cardiomyopathy Across Species Reveals Conservation of Biological Process But Not Gene Expression
Authors: Ali Samia A. , Perera Gayani , Laird Jason , Batorsky Rebecca , Maron Martin S. , Rivas Victor N. , Stern Joshua A. , Harris Samantha , Chin Michael T. 
Published: December 2024

Background

Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease where the most frequently associated mutations occur in the myosin‐binding protein C (
MYBPC3
) sarcomere‐associated gene. HCM is also a common veterinary clinical problem in certain cat breeds such as Maine Coons and Ragdolls, also most associated with mutations in
MYBPC3
. Mouse models of HCM in which
Mybpc3
mutations are introduced recapitulate some, but not all, features of human HCM.

Methods and Results

To elucidate the common and distinctive pathological pathways across species and foster a greater understanding of the concordance of mouse HCM models to clinical
mybpc3
‐associated HCM, we generated single nuclei RNA‐sequencing data sets from feline, human, and murine heart tissue carrying
MYBPC3
variants. Numerous genes were differentially expressed between mutation positive and mutation negative cell types within each species, identified using the model‐based analysis of single‐cell transcriptomics algorithm. Gene Ontology enrichment analysis of differentially expressed genes in cardiomyocytes across species revealed alterations in genes involved in muscle development, muscle contraction, muscle hypertrophy, regulation of sarcoplasmic calcium release, ATP metabolic process, and oxidative phosphorylation.

Conclusions
These common biological processes across species are consistent with known phenotypic aspects of HCM such as hypertrophy, hypercontractility, diastolic dysfunction, and altered energy metabolism. Surprisingly, among conserved biological processes within cardiomyocytes across species, the individual genes driving the biological processes were distinct. This work to identify common and species‐specific disease‐promoting pathway differences will allow development of targeted therapies for both human and veterinary application and will facilitate an understanding of the idiosyncrasies of mouse models.
Prognostic Implication of Computational Angiography–Derived Fractional Flow Reserve in Patients With Nonobstructive Coronary Artery Disease
Authors: Hung Yik‐Ming , Xuan Hao‐Chen , Ren Qing‐Wen , Huang Jia‐Yi , Yu Si‐Yeung , Tse Yi‐Kei , Zhang Jing‐Nan , Gu Wen‐Li , Guo Ran , Leung Calvin Ka‐Lam , Yiu Kai‐Hang 
Published: December 2024

Background
Risk stratification of patients with symptomatic nonobstructive coronary artery disease remains uncertain. Our study assessed the clinical value of single‐vessel, multivessel, and 3‐vessel computational angiography–derived fractional flow reserve (caFFR) measurement in patients with nonobstructive coronary artery disease.

Methods and Results

We enrolled patients with ≤50% stenosis with a caFFR value ≥0.8 in all 3 coronary arteries on coronary angiography. The sum of caFFR values in the 3 vessels was computed for each patient. Patient stratification was based on the median value of the following criteria: single‐vessel analysis, multivessel analysis, and 3‐vessel analysis. The primary end point of this study was major adverse cardiac events at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization. A total of 490 patients were included. The 5‐year major adverse cardiac event rates in single‐vessel analysis were statistically insignificant between low‐ and high‐caFFR groups (left anterior descending artery [
P
=0.163]; left circumflex artery [
P
=0.797]; right coronary artery [
P
=0.127]). In multivessel analysis, patients in the multiple‐vessel low‐caFFR group (with 2–3 vessels lower than median value of all coronary arteries) showed an increased risk of 5‐year major adverse cardiac events compared with patients in the single‐vessel low‐caFFR group (0–1 vessel) (hazard ratio [HR], 2.648 [95% CI, 1.141–6.145];
P
=0.023). In 3‐vessel analysis, patients in the low 3‐vessel caFFR group demonstrated a greater 5‐year major adverse cardiac event risk than the high 3‐vessel caFFR group (HR, 2.43 [95% CI, 1.087–5.433];
P
=0.031).

Conclusions
We demonstrated that both multiple‐vessel and 3‐vessel caFFR measurements serve as valuable prognostic indicators for risk assessment in patients with nonobstructive coronary artery disease.
Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
Authors: Milani Paolo , Sanna Giuseppe Damiano , Mussinelli Roberta , Basset Marco , Guida Gianluigi , Attanasio Andrea , Nanci Martina , Fabris Francesca , Bellofiore Claudia , Fogliani Alessandro , Novello Elisa , Benigna Francesca , Obici Laura , Benvenuti Pietro , Ciardo Martina , Nuvolone Mario , Averaimo Manuela , Casu Gavino , Foli Andrea , Perlini Stefano , Merlini Giampaolo , Palladini Giovanni 
Published: December 2024

Background
For the time being, tafamidis is the only approved treatment for wild‐type transthyretin cardiac amyloidosis. However, benefits on all‐cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months.

Methods and Results

We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group–Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild‐type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow‐up was 43 months, and 367 patients (53%) died. Eighteen‐month death was predicted by NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group–Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard‐ and high‐risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (
P
<0.001). This was confirmed in the validation set.

Conclusions
A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group–Performance Status identifies subjects with cardiac wild‐type transthyretin cardiac amyloidosis at high risk of early death.
Multiparametric Assessment of Right Ventricular Dysfunction in Heart Failure: An Analysis From PARAGON‐HF
Authors: Lu Henri , Inciardi Riccardo M. , Abanda Martin , Shah Amil M. , Cikes Maja , Claggett Brian L. , Prasad Narayana , Lam Carolyn S. P. , Redfield Margaret , McMurray John J. V. , Pfeffer Marc A. , Solomon Scott D. , Hegde Sheila M. , Skali Hicham 
Published: December 2024

Background
This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.

Methods and Results
Data from 809 patients in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.7 cm, fractional area change <35% or absolute RV free wall longitudinal strain <20%) were identified using multivariable logistic regression models. We further assessed the prognostic value of the number of abnormal RV parameters (0, 1, ≥2) on total HF hospitalizations (HFH) and cardiovascular death, total HFH, first HFH or cardiovascular death, all‐cause death, and cardiovascular death. RVD was identified in 461 (57%) patients. Correlates of RVD included older age, higher heart rate, atrial fibrillation/flutter, greater left ventricle wall thickness, higher N‐terminal pro‐B‐type natriuretic peptide levels, lower systolic blood pressure, and lower left ventricle absolute global longitudinal strain. These results were consistent across sexes, except atrial fibrillation/flutter and LV wall thickness, which were associated with a higher risk of RVD in men but not in women. Participants with ≥2 abnormal RV parameters had a significantly higher adjusted risk of total HFH and cardiovascular death (rate ratio, 2.13 [95% CI, 1.13–4.01]), first HFH or cardiovascular death, all‐cause death, and cardiovascular death. Conversely, an isolated abnormal RV parameter was not associated with a worse outcome.

Conclusions
RV measures may underestimate the burden of RVD in HF with preserved ejection fraction when considered in isolation. Clinicians should consider multiple dimensions to comprehensively assess RV function in patients with HF with preserved ejection fraction.
Cardiovascular and Metabolic Effects of Modulating Circulating Ketone Bodies With 1,3‐Butanediol in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Guldbrandsen Halvor , Gopalasingam Nigopan , Christensen Kristian Hylleberg , Hørsdal Oskar Kjærgaard , Nielsen Roni , Wiggers Henrik , Berg‐Hansen Kristoffer 
Published: December 2024

Background
Oral treatment with the exogenous ketone body 3‐hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4 hours. Treatment with (R)‐1,3‐butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.

Methods and Results

This was a randomized, single‐blind, placebo‐controlled, crossover study. Transthoracic echocardiography and venous blood samples were performed at baseline and hourly for 6 hours after an oral dose of BD (0.5 g/kg) or taste‐matched placebo. The primary end point was the average between‐treatment difference in cardiac output during the 6‐hour period after intake. Secondary end points were stroke volume, heart rate, left ventricular ejection fraction, circulating 3‐hydroxybutyrate, and free fatty acids. Twelve patients with heart failure with reduced ejection fraction were included. BD treatment provided significant increase in circulating 3‐hydroxybutyrate by 1400 μmol/L (95% CI, 1262–1538 μmol/L,
P
<0.001) and increased cardiac output by 0.9 L/min (95% CI, 0.7–1.1 L/min,
P
<0.001) compared with placebo. Stroke volume increased by 15 mL (95% CI, 11–19 mL,
P
<0.001), and heart rate remained similar between treatments (
P
=0.150). Left ventricular ejection fraction increased by 3 percentage points (95% CI, 1–4 percentage points,
P
<0.001). Global longitudinal strain improved (
P
<0.001). Left ventricular contractility estimates increased after BD intake, and parameters of afterload were reduced. Finally, free fatty acids and glucose levels decreased.

Conclusions
Oral dosing of BD led to prolonged ketosis and cardiovascular and metabolic benefits in patients with heart failure with reduced ejection fraction. Treatment with BD is an attractive option to achieve beneficial effects from sustained therapeutic ketosis.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05768100.
Computational Literary Studies in the Context of Contemporary Czech Literary Studies – Especially the Concept of the Corpus of Czech Novels
Authors: Změlík Richard 
Published: December 2024

The paper discusses some issues related to the field called computational literary studies (CLS), which belongs to the digital humanities. The introduction deals mainly with the Czechoslovak literary and partly linguistic tradition that preceded this discipline. The author then introduces Czech projects that represent specialised literary corpora, in particular focusing on the emerging corpus and web application of the Czech Corpus of Prose, describing its overall structure, individual parameters and specific functions.
Transitioning From Pediatric to Adult Psychiatric Care for ADHD in Sweden: A Nationwide Study
Authors: Giacobini MaiBritt , Zhao Jingcheng , Freilich Jonatan , Malmgren Carolina , Wallin Bernhardsson Niklas , Ahnemark Ewa 
Published: December 2024

Objective: To evaluate care transition and medication use in young adults with ADHD in Sweden. Method: Observational retrospective study of patients with ADHD from the Swedish National Patient Register, Prescribed Drug Register, and Cause of Death Register (2018–2020). Last contact with pediatric psychiatric care, first contact with adult psychiatric care, and medication use were described for ages 18 to 21 years, inclusive. Results: Of 19,233 patients who had dispensed ADHD treatment, 85.8% had received adult psychiatric care by 21 years of age. The proportion of patients on medication was highest at age 18 years (80.1%), decreasing to 36.1% by age 21 years. By 21 years, there were significantly more patients on versus off ADHD medication who had received healthcare for autism, been prescribed selective serotonin re-uptake inhibitors, and received adult psychiatric outpatient visits (all p < .0001). Conclusion: This study demonstrates declining ADHD medication use during the pediatric-to-adult care transition for patients in Sweden.