bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Prediction in Male Adolescents With Congenital Long QT Syndrome: Implications for Sex‐Specific Risk Stratification in Potassium Channel‐Mediated Long QT Syndrome
Authors: Bjelic Milica , Goldenberg Ido , Younis Arwa , Chen Anita Y. , Huang David T. , Yoruk Ayhan , Aktas Mehmet K. , Rosero Spencer , Cutter Kristina , McNitt Scott , Sotoodehnia Nona , Kudenchuk Peter J. , Rea Thomas D. , Arking Dan E. , Zareba Wojciech , Ackerman Michael J. , Goldenberg Ilan 
Published: January 2024

Background
Sex‐specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life‐threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel‐mediated LQTS.

Methods and Results

The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. Anderson‐Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow‐up. The genotype–phenotype risk prediction model identified low‐, intermediate‐, and high‐risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low‐risk group, high‐risk male subjects experienced a pronounced 5.2‐fold increased risk of recurrent CEs (
P
<0.001), whereas intermediate‐risk patients had a 2.1‐fold (
P
=0.004) increased risk . At age 20 years, the low‐, intermediate‐, and high‐risk adolescent male patients had on average 0.3, 0.6, and 1.4 CEs per person, respectively. Corresponding 10‐year adjusted probabilities for a first LTE were 2%, 6%, and 8%.

Conclusions
Personalized genotype–phenotype risk estimates can be used to guide sex‐specific management in male adolescents with potassium channel‐mediated LQTS.
Mitral Annulus Calcium Score in Patients With Calcific Mitral Stenosis Undergoing Invasive Hemodynamic Assessment
Authors: El Sabbagh Abdallah , Parikh Pragnesh , Ray Jordan , Nishimura Rick A. , Pislaru Sorin V. , Pellikka Patricia A. , Guerrero Mayra , Hochwald Alexander , Miranda William R. 
Published: January 2024

Background
Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown.

Methods and Results

This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm
2
. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (
P
=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (
r
=0.07;
P
=0.6) or mitral valve gradient (
r
=−0.03;
P
=0.8).

Conclusions
MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC‐related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.
Role of Cerebral Embolic Protection Devices in Patients Undergoing Transcatheter Aortic Valve Replacement: An Updated Meta‐Analysis
Authors: Kaur Arpanjeet , Dhaliwal Arshdeep S. , Sohal Sumit , Gwon Yeongjin , Gupta Soumya , Bhatia Kirtipal , Dominguez Abel Casso , Basman Craig , Tamis‐Holland Jacqueline 
Published: January 2024

Background
Cerebral embolic protection devices (CEPD) capture embolic material in an attempt to reduce ischemic brain injury during transcatheter aortic valve replacement. Prior reports have indicated mixed results regarding the benefits of these devices. With new data emerging, we performed an updated meta‐analysis examining the effect of CEPD during transcatheter aortic valve replacement on various clinical, neurological, and safety parameters.

Methods and Results
A comprehensive review of electronic databases was performed comparing CEPD and no‐CEPD in transcatheter aortic valve replacement. Primary clinical outcome was all‐cause stroke. Secondary clinical outcomes were disabling stroke and all‐cause mortality. Neurological outcomes included worsening of the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score from baseline at discharge, presence of new ischemic lesions, and total lesion volume on neuroimaging. Safety outcomes included major or minor vascular complications and stage 2 or 3 acute kidney injury. Seven randomized controlled trials with 4016 patients met the inclusion criteria. There was no statistically significant difference in the primary clinical outcome of all‐cause stroke; secondary clinical outcomes of disabling stroke, all‐cause mortality, neurological outcomes of National Institutes of Health Stroke Scale score worsening, Montreal Cognitive Assessment worsening, presence of new ischemic lesions, or total lesion volume on diffusion‐weighted magnetic resonance imaging between CEPD versus control groups. There was no statistically significant difference in major or minor vascular complications or stage 2 or 3 acute kidney injury between the groups.

Conclusions
The use of CEPD in transcatheter aortic valve replacement was not associated with a statistically significant reduction in the risk of clinical, neurological, and safety outcomes.
One‐Year Disability Trajectories and Long‐Term Cardiovascular Events, Recurrent Stroke, and Mortality After Ischemic Stroke
Authors: Du Jigang , Zhai Yujia , Dong Wenjing , Che Bizhong , Miao Mengyuan , Peng Yanbo , Ju Zhong , Xu Tan , He Jiang , Zhang Yonghong , Zhong Chongke 
Published: January 2024

Background
Patients with stroke are often affected by varying degrees of functional disability and have different evolution patterns in functional disability. However, little is known about the predictive usefulness of disability changes after stroke. We aimed to describe 1‐year disability trajectories and to assess the associations of longitudinal disability trajectories with 24‐month clinical outcomes after ischemic stroke.

Methods and Results
A total of 3533 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were studied. Distinct trajectories of disability were identified by the group‐based trajectory model, as measured by modified Rankin Scale score within 12 months. Cox proportional hazards regression models were used to examine the associations of disability trajectories with 24‐month cardiovascular events and all‐cause mortality. We identified 4 distinct disability trajectories: no significant disability (562 participants [15.9%]), slight disability to recovery (1575 participants [44.6%]), severe to moderate disability (1087 participants [30.8%]), and persistent severe disability (309 participants [8.7%]). Compared with no significant disability trajectory, the multivariable adjusted hazard ratios (95% CIs) of patients within the persistent heavy–severe trajectory were 2.63 (1.20–5.76) for cardiovascular events, 2.55 (1.12–5.79) for recurrent stroke, and 6.10 (2.22–16.72) for all‐cause mortality; notably, the hazard ratios (95% CIs) for patients within the severe to moderate disability trajectory were 1.99 (1.01–3.94) for cardiovascular events and 1.85 (1.03–3.33) for the composite outcome of cardiovascular events and all‐cause mortality.

Conclusions
Functional disability trajectories within 12 months after stroke onset were associated with the risk of 24‐month adverse outcomes. Patients with persistent severe disability or severe to moderate disability had higher risk of cardiovascular events and all‐cause mortality.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier:
NCT01840072
Primary and Secondary Cardiovascular and Kidney Prevention With Canagliflozin: Insights From the CANVAS Program and CREDENCE Trial
Authors: Sharma Abhinav , Razaghizad Amir , Joury Abdulaziz , Levin Adeera , Bajaj Harpreet S. , Mancini G. B. John , Wong Norman C. , Slee April , Ang Fernando G. , Rapattoni Wally , Neuen Brendon L. , Arnott Clare , Perkovic Vlado , Mahaffey Kenneth W. 
Published: January 2024

Background
This study evaluated the effects of canagliflozin in patients with type 2 diabetes with and without prevalent cardiovascular disease (secondary and primary prevention).

Methods and Results

This was a pooled participant‐level analysis of the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. The CANVAS Program included participants with type 2 diabetes at elevated cardiovascular risk, whereas the CREDENCE trial included participants with type 2 diabetes and albuminuric chronic kidney disease. Hazard ratios (HRs) with interaction terms were obtained from Cox regression models to estimate relative risk reduction with canagliflozin versus placebo across the primary and secondary prevention groups. We analyzed 5616 (38.9%) and 8804 (61.1%) individuals in the primary and secondary prevention subgroups, respectively. Primary versus secondary prevention participants were on average younger (62.2 versus 63.8 years of age) and more often women (42% versus 31%). Canagliflozin reduced the risk of major adverse cardiovascular events (HR, 0.84 [95% CI, 0.76–0.94]) consistently across primary and secondary prevention subgroups (
P
interaction
=0.86). Similarly, no treatment effect heterogeneity was observed with canagliflozin for hospitalization for heart failure, cardiovascular death, end‐stage kidney disease, or all‐cause mortality (all
P
interaction
>0.5).

Conclusions
Canagliflozin reduced cardiovascular and kidney outcomes with no statistical evidence of heterogeneity for the treatment effect across the primary and secondary prevention subgroups in the CANVAS Program and CREDENCE trial. Although studies on the optimal implementation of canagliflozin within these populations are warranted, these results reinforce canagliflozin's role in cardiorenal prevention and treatment in individuals with type 2 diabetes.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.
Administrative Model for Profiling Hospital Performance on Coronary Artery Bypass Graft Surgery: Based on the Chinese Hospital Quality Monitoring System
Authors: Su Xiaoting , Zhang Danwei , Gu Dachuan , Rao Chenfei , Chen Sipeng , Fan Jing , Zheng Zhe 
Published: January 2024

Background
We aimed to develop an administrative model to profile the performance on the outcomes of coronary artery bypass grafting across hospitals in China.

Methods and Results

This retrospective study was based on the Chinese Hospital Quality Monitoring System (HQMS) from 2016 to 2020. The coronary artery bypass grafting cases were identified by procedure code, and those of 2016 to 2017 were randomly divided into modeling and validation cohorts, while those in other years were used to ensure the model stability across years. The outcome was discharge status as “death or withdrawal,” and that withdrawal referred to discharge without medical advice when patients were in the terminal stage but reluctant to die in the hospital. Candidate covariates were mainly identified by diagnoses or procedures codes. Patient‐level logistic models and hospital‐level hierarchical models were established. A total of 203 010 coronary artery bypass grafts in 699 hospitals were included, with 60 704 and 20 233 cases in the modeling and validation cohorts and 40 423, 42 698, and 38 952 in the years 2018, 2019, and 2020, respectively. The death or withdrawal rate was 3.4%. The areas under the curve were 0.746 and 0.729 in the patient‐level models of modeling and validation cohorts, respectively, with good calibration and stability across years. Hospital‐specific risk‐standardized death or withdrawal rates were 2.61% (interquartile range, 1.87%–3.99%) and 2.63% (interquartile range, 1.97%–3.44%) in the modeling and validation cohorts, which were highly correlated (correlation coefficient, 0.96;
P
<0.001). Between‐hospital variations were distinguished among hospitals of different volumes and across years.

Conclusions
The administrative model based on Hospital Quality Monitoring System could profile hospital performance on coronary artery bypass grafting in China.
Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR‐155‐5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels
Authors: Zhao Meng , Lei Jiahui , Deng Fengying , Zhao Chenxuan , Xu Ting , Ji Bingyu , Fu Mengyu , Wang Xietong , Sun Miao , Zhang Meihua , Gao Qinqin 
Published: January 2024

Background
Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid‐late pregnancy, it is urgent to further explore whether it affects the long‐term synthesis of NO in offspring vascular endothelial cells.

Methods and Results

Pregnant Sprague–Dawley rats were housed in a normoxic or hypoxic (10.5% O
2
) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO‐dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine‐induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR‐155‐5p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis.

Conclusions
The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR‐155‐5p/NADPH oxidase 2/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.
Interleukin 17A Contributes to Blood‐Brain Barrier Disruption of Hypothalamic Paraventricular Nucleus in Rats With Myocardial Infarction
Authors: Yu Yang , Weiss Robert M. , Wei Shun‐Guang 
Published: January 2024

Background
Elevated inflammatory cytokines in the periphery have been identified as active contributors to neuroinflammation and sympathetic overactivity in heart failure (HF). Yet, the exact mechanisms by which these cytokines breach the blood‐brain barrier (BBB) to exert their effects on the brain remain elusive. Interleukin 17A has been linked to BBB disruption in various neurologic disorders, and its levels were significantly augmented in circulation and the brain in HF. The present study aimed to determine whether the BBB integrity was compromised within the hypothalamic paraventricular nucleus (PVN), and if so, whether interleukin 17A contributes to BBB disruption in myocardial infarction–induced HF.

Methods and Results
Male Sprague‐Dawley rats underwent coronary artery ligation to induce HF or sham surgery. Some HF rats received bilateral PVN microinjections of an interleukin 17 receptor A small interfering RNA or a scrambled small interfering RNA adeno‐associated virus. Four weeks after coronary artery ligation, the permeability of the BBB was evaluated by intracarotid injection of fluorescent dyes (fluorescein isothiocyanate–dextran 10 kDa+rhodamine‐dextran 70 kDa). Compared with sham‐operated rats, HF rats exhibited an elevated extravasation of fluorescein isothiocyanate–dextran 10 kDa within the PVN but not in the brain cortex. The plasma interleukin 17A levels were positively correlated with fluorescein isothiocyanate 10 kDa extravasation in the PVN. The expression of caveolin‐1, a transcytosis marker, was augmented, whereas the expression of tight junction proteins was diminished in HF rats. Interleukin 17 receptor A was identified within the endothelium of PVN microvessels. Treatment with interleukin 17 receptor A small interfering RNA led to a significant attenuation of fluorescein isothiocyanate 10 kDa extravasation in the PVN and reversed expression of caveolin‐1 and tight junction–associated proteins in the PVN.

Conclusions
Collectively, these data indicate that BBB permeability within the PVN is enhanced in HF and is likely attributable to increased interleukin 17A/interleukin 17 receptor A signaling in the BBB endothelium, by promoting caveolar transcytosis and degradation of tight junction complexes.
Optimizing ASReview Simulations: A generic Multiprocessing Solution for ‘Light-data’ and ‘Heavy-data’ Users
Authors: Romanov Sergei , Siqueira Abel Soares , de Bruin Jonathan , Teijema Jelle , Hofstee Laura , van de Schoot Rens 
Published: January 2024

ABSTRACT
Active learning can be used for optimizing and speeding up the screening phase of systematic reviews. Running simulation studies mimicking the screening process can be used to test the performance of different machine-learning models or to study the impact of different training data. This paper presents an architecture design with a multiprocessing computational strategy for running many such simulation studies in parallel, using the ASReview Makita workflow generator and Kubernetes software for deployment with cloud technologies. We provide a technical explanation of the proposed cloud architecture and its usage. In addition to that, we conducted 1140 simulations investigating the computational time using various numbers of CPUs and RAM settings. Our analysis demonstrates the degree to which simulations can be accelerated with multiprocessing computing usage. The parallel computation strategy and the architecture design that was developed in the present paper can contribute to future research with more optimal simulation time and, at the same time, ensure the safe completion of the needed processes.
‘Solving’ the Paradox of the Odyssean Ethiopians’ Twin Dual Localization
Authors: Gordon Joel 
Published: January 2024

Abstract
This paper considers the narrative significance of localization in Homer’s Odyssey, in particular singular places that are associated with multiple spaces (identified here as dual localization). Our reading posits that spatial features hold narrative significance and, once uncovered, this resolves ‘problematic’ issues that may arise from spatial paradoxes. The chosen case study is the Odyssean land of the Ethiopians with its twin dual localization: (1) it is located simultaneously at the eastern and western peripheries of the world while also located singularly ‘with Poseidon’; and (2) this peripheral localization contrasts with a later ‘real world’ setting in Egypt/North Africa. While this people’s localization has been the subject of prior study, this paper presents a novel analysis: these localizations serve a characterizing function which, in turn, relates to the thematic function of Menelaus’ embedded narrative as foreshadowing the primary narrative of Odysseus’ nostos.
On Prodicus and the Derveni Papyrus
Authors: Henry John 
Published: January 2024

Abstract
Another identification for the author of the Derveni papyrus has been suggested: the fifth-century BCE sophist Prodicus of Ceos. Producing over 18 testimonia, Lebedev argues that the Derveni papyrus and the thought of Prodicus agree on many points that have previously been disregarded, including their linguistic approach and cosmological doctrines. On the basis of this evidence, it is suggested that Prodicus wrote the Derveni papyrus as an atheistic polemic and a sophistic deconstruction of popular religion. However, this article will suggest that the testimonia does not establish the case, and consequently the authorship of the Derveni papyrus remains undetermined.
The Stirring Tropics: The Ubiquity of Moisture Modes and Moisture–Vortex Instability
Authors: Mayta Víctor C. , Adames Corraliza Ángel F. 
Published: January 2024

Abstract
Observations of column water vapor in the tropics show significant variations in space and time, indicating that it is strongly influenced by the passage of weather systems. It is hypothesized that many of the influencing systems are moisture modes, systems whose thermodynamics are governed by moisture. On the basis of four objective criteria, results suggest that all oceanic convectively coupled tropical depression (TD)-like waves and equatorial Rossby waves are moisture modes. These modes occur where the horizontal column moisture gradient is steep and not where the column water vapor content is high. Despite geographical basic-state differences, the moisture modes are driven by the same mechanisms across all basins. The moist static energy (MSE) anomalies propagate westward by horizontal moisture advection by the trade winds. Their growth is determined by the advection of background moisture by the anomalous meridional winds and anomalous radiative heating. Horizontal maps of column moisture and 850-hPa streamfunction show that convection is partially collocated with the low-level circulation in nearly all the waves. Both this structure and the process of growth indicate that the moisture modes grow from moisture–vortex instability. Last, space–time spectral analysis reveals that column moisture and low-level meridional winds are coherent and exhibit a phasing that is consistent with a poleward latent energy transport. Collectively, these results indicate that moisture modes are ubiquitous across the tropics. That they occur in regions of steep horizontal moisture gradients and grow from moisture–vortex instability suggests that these gradients are inherently unstable and are subject to continuous stirring.

Significance Statement
Over the tropics, column water vapor has been found to be highly correlated with precipitation, especially in slowly evolving systems. These observations and theory support the hypothesis that moisture modes exist, a type of precipitating weather system that does not exist in dry theory. In this study, we found that all oceanic tropical depression (TD)-like waves and equatorial Rossby waves are moisture modes. These systems exist in regions where moisture varies greatly in space, and they grow by transporting air from the humid areas of the tropics toward their low pressure center. These results indicate that the climatological-mean distribution of moisture in the tropics is unstable and is subject to stirring by moisture modes.