bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the American Heart Association/American College of Cardiology Guideline—Recommended and Contemporary Pretest Probability Models in a Mixed Asian Cohort: The Contribution of Coronary Artery Calcium
Authors: Baskaran Lohendran , Yan Linxuan , Tan Chun S. , Ho Woon W. , Tan Swee Y. , Williams Michelle C. , Han Donghee , Nakanishi Rine , Cerci Rodrigo J. , Ng Ming‐Yen , Shaw Leslee J. , Chua Terrance S. J. , Douglas Pamela , Winther Simon 
Published: June 2024

Background

Most pretest probability (PTP) tools for obstructive coronary artery disease (CAD) were Western ‐developed. The most appropriate PTP models and the contribution of coronary artery calcium score (CACS) in Asian populations remain unknown. In a mixed Asian cohort, we compare 5 PTP models: local assessment of the heart (LAH), CAD Consortium (CAD2), risk factor‐weighted clinical likelihood, the American Heart Association/American College of Cardiology and the European Society of Cardiology PTP and 3 extended versions of these models that incorporated CACS: LAH
(CACS)
, CAD2
(CACS)
, and the CACS‐clinical likelihood.

Methods and Results

The study cohort included 771 patients referred for stable chest pain. Obstructive CAD prevalence was 27.5%. Calibration, area under the receiver‐operating characteristic curves (AUC) and net reclassification index were evaluated. LAH clinical had the best calibration (χ
2
5.8;
P
=0.12). For CACS models, LAH
(CACS)
showed least deviation between observed and expected cases (χ
2
37.5;
P
<0.001). There was no difference in AUCs between the LAH clinical (AUC, 0.73 [95% CI, 0.69–0.77]), CAD2 clinical (AUC, 0.72 [95% CI, 0.68–0.76]), risk factor‐weighted clinical likelihood (AUC, 0.73 [95% CI: 0.69–0.76) and European Society of Cardiology PTP (AUC, 0.71 [95% CI, 0.67–0.75]). CACS improved discrimination and reclassification of the LAH
(CACS)
(AUC, 0.88; net reclassification index, 0.46), CAD2
(CACS)
(AUC, 0.87; net reclassification index, 0.29) and CACS‐CL (AUC, 0.87; net reclassification index, 0.25).

Conclusions
In a mixed Asian cohort, Asian‐derived LAH models had similar discriminatory performance but better calibration and risk categorization for clinically relevant PTP cutoffs. Incorporating CACS improved discrimination and reclassification. These results support the use of population‐matched, CACS‐inclusive PTP tools for the prediction of obstructive CAD.
Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS
Authors: Lu Guangdong , Wang Tao , Sun Xinyi , Yang Renjie , Luo Jichang , Tong Xiaoguang , Gu Yuxiang , Wang Jiyue , Tong Zhiyong , Kuai Dong , Cai Yiling , Ren Jun , Wang Donghai , Duan Lian , Maimaitili Aisha , Hang Chunhua , Yu Jiasheng , Ma Yan , Liu Sheng , Jiao Liqun , Ling Feng , Wang Haibo , Amin‐Hanjani Sepideh , Bai Xuesong , Powers William J. , Derdeyn Colin P. , Wu Yangfeng 
Published: June 2024

Background
The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion.

Methods and Results

We analyzed the association between qualifying event—the latest ischemic event (transient ischemic attack [TIA] or stroke)—and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%,
P
=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%,
P
=0.86) or stroke (6.7% versus 8.9%,
P
=0.55).

Conclusions
Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01758614.
Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C‐Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury
Authors: Wei Tian‐Wen , Shan Tian‐Kai , Wang Hao , Chen Jia‐Wen , Yang Tong‐Tong , Zhou Liu‐Hua , Zhao Di , Sun Jia‐Teng , Wang Si‐Bo , Gu Ling‐Feng , Du Chong , Jiang Qi‐Qi , Sun Rui , Wang Qi‐Ming , Kong Xiang‐Qing , Lu Xiao‐Hu , Sun Hao‐Liang , Xu Yi , Xie Li‐Ping , Gu Ai‐Hua , Chen Feng , Ji Yong , Guo Xue‐Jiang , Wang Lian‐Sheng 
Published: June 2024

Background
The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell‐cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine.

Methods and Results
Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co‐Immunoprecipitation (Co‐IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO‐IP experiments. Results showed that the 1–265 domain of CHK1 directly binds to the 157–400 amino acids of PKM2. Furthermore, hiPSC‐CM (human iPS cell‐derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C‐domain‐mediated cardiac metabolic reprogramming.

Conclusions
This study demonstrates that the 1–265 amino acid domain of CHK1 binds to the 157–400 domain of PKM2 and activates PKM2‐mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.
miR‐193b‐3p and miR‐346 Exert Antihypertensive Effects in the Rostral Ventrolateral Medulla
Authors: Zhang Shuai , Wang Xueping , Dai Tengteng , Tong Lei , Chen Gaojun , Wang Linping , Ren Zhangyan , Liu Haisheng , Du Dongshu 
Published: June 2024

Background
Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological processes, but their influence on RVLM neuronal excitability and blood pressure (BP) remains widely unexplored.

Methods and Results

The RVLM miRNA profiles in spontaneously hypertensive rats were unveiled using RNA sequencing. Potential effects of these miRNAs in reducing neuronal excitability and BP and underlying mechanisms were investigated through various experiments. Six hundred thirty‐seven miRNAs were identified, and reduced levels of miR‐193b‐3p and miR‐346 were observed in the RVLM of spontaneously hypertensive rats. Increased miR‐193b‐3p and miR‐346 expression in RVLM lowered neuronal excitability, sympathetic outflow, and BP in spontaneously hypertensive rats. In contrast, suppressing miR‐193b‐3p and miR‐346 expression in RVLM increased neuronal excitability, sympathetic outflow, and BP in Wistar Kyoto and Sprague‐Dawley rats. Cdc42 guanine nucleotide exchange factor (
Arhgef9)
was recognized as a target of miR‐193b‐3p. Overexpressing miR‐193b‐3p caused an evident decrease in
Arhgef9
expression, resulting in the inhibition of neuronal apoptosis. By contrast, its downregulation produced the opposite effects. Importantly, the decrease in neuronal excitability, sympathetic outflow, and BP observed in spontaneously hypertensive rats due to miR‐193b‐3p overexpression was greatly counteracted by
Arhgef9
upregulation.

Conclusions

miR‐193b‐3p and miR‐346 are newly identified factors in RVLM that hinder hypertension progression, and the miR‐193b‐3p/
Arhgef9
/apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.
Symptoms of COPD in the absence of airflow obstruction are more indicative of pre-COPD than overdiagnosis
Authors: Spittle Daniella A. , Thomas Maximillian , Stevens Caitlin , Gazwani Abdulrhman , Fenton Sally , De Soyza Joshua , Turner Alice M. 
Published: June 2024

BackgroundDysfunction of the small airways is a precursor of COPD but is not detectable on standard spirometric testing until significant destruction has occurred. A proportion of COPD patients have a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 which is greater than the lower limit of normal (LLN), when adjusted for their age and sex. It is not understood whether this group of patients, known as “discordant COPD”, are representative of “early COPD” or overdiagnosis.MethodsWe sought to characterise discordant COPD (disCOPD) using radiology, lung function, serum biomarkers, activity monitoring and quality-of-life scores, comparing with COPD patients with an FEV1/FVC <0.7 and <LLN and healthy, age-matched controls.ResultsSix out of eight serum biomarkers were significantly different in the disCOPD groupversushealthy controls, as were the scores of all four quality-of-life questionnaires. Activity monitoring revealed similar levels of sedentary time between the disCOPD group and concordant COPD (conCOPD). Computed tomography analysis showed less involvement of small airway dysfunction and emphysema in the disCOPD groupversusconCOPD.ConclusionsCollectively, our findings support the hypothesis that disCOPD is a clinically relevant phenomenon that represents a pre-COPD state. Identification of such patients is important for early intervention and management before progression to fully established COPD.
Impact analysis of Advanced Driver Assistance Systems (ADAS) regarding road safety – computing reduction potentials
Authors: Aleksa Michael , Schaub Andrea , Erdelean Isabela , Wittmann Stephan , Soteropoulos Aggelos , Fürdös Alexander 
Published: June 2024

AbstractIn the present study road safety impact analysis for certain advanced driver assistance systems (ADAS) was conducted. Based on a literature review, expert interviews and current adaptations in legislation, the most promising nine ADAS were selected. The impact was analysed based on statistical crash data from Austria. Factors such as infrastructure and weather conditions, market penetration, expected functionality of sensors, user acceptance and risk homeostasis were considered. A software tool was developed to calculate the crash reduction potential of the selected ADAS for the scenarios 2025, 2030 and 2040.The results show that the ADAS related to warning/braking have the greatest future reduction potential and could lead to a reduction of up to 8,700 crashes and 70 fatalities in Austria in 2040. In addition, the Intelligent Speed Assistance system would lead to an overall crash reduction of 8% compared to current crash numbers in Austria in 2040. The Turning Assistant for heavy goods vehicles shows the lowest reduction in crashes and casualties, but due to the highest severity per crash (93 fatalities per 1,000 crashes), it nevertheless provides an important contribution to the reduction of fatalities in road traffic.However, to benefit from the ADAS safety potential, it is highly relevant that these systems are used in a correct manner. In the future, it will be necessary to provide users with more information on the correct use, benefits and limitations of the respective ADAS and to integrate the use of these systems into driver education procedures and tests.
Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data
Authors: Yan Zhaoqi , Xu Yifeng , Li Keke , Liu Liangji 
Published: June 2024

Abstract
Background
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior—specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD.

Methods
Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared “pleiotropic SNPs” between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD.

Results
Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel “pleiotropic SNPs” (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk.

Conclusion
We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.
GmHXK2 promotes the salt tolerance of soybean seedlings by mediating AsA synthesis, and auxin synthesis and distribution
Authors: Guo Yuqi , Liu Chang , Chen Shuai , Tian Zengyuan 
Published: June 2024

Abstract
Background
Salt is an important factor that affects crop productivity. Plant hexokinases (HXKs) are key enzymes in the glycolytic pathway and sugar signaling transduction pathways of plants. In previous studies, we identified and confirmed the roles of GmHXK2 in salt tolerance.

Results
In this study, we analyzed the tissue-specific expression of GmHXK2 at different growth stages throughout the plant’s life cycle. The results showed that GmHXK2 was expressed significantly in all tissues at vegetative stages, including germination and seedling. However, no expression was detected in the pods, and there was little expression in flowers during the later mature period. Arabidopsis plants overexpressing the GmHXK2 (OE) had more lateral roots. The OE seedlings also produced higher levels of auxin and ascorbic acid (AsA). Additionally, the expression levels of genes PMM, YUC4/YUC6/YUC8, and PIN/LAX1,LAX3, which are involved respectively in the synthesis of AsA and auxin, as well as polar auxin transport, were upregulated in OE plants. This upregulation occurred specifically under exogenous glucose treatment. AtHKT1, AtSOS1, and AtNHX1 were up-regulated in OE plants under salt stress, suggesting that GmHXK2 may modulate salt tolerance by maintaining ion balance within the cells and alleviating damage caused by salt stress. Additionally, we further confirmed the interaction between GmHXK2 and the protein GmPMM through yeast two-hybridization and bimolecular fluorescence complementation assays, respectively.

Conclusion
The expression of GmHXK2 gene in plants is organ-specific and developmental stage specific. GmHXK2 not only regulates the synthesis of AsA and the synthesis and distribution of auxin, but also promotes root elongation and induces lateral root formation, potentially enhancing soil water absorption. This study reveals the crosstalk between sugar signaling and hormone signaling in plants, where GmHXK2 acts as a glucose sensor through its interaction with GmPMM, and sheds light on the molecular mechanism by which GmHXK2 gene is involved in salt tolerance in plants.
Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study
Authors: Liu Rong , Xu Li ang , Zhao Ziqi , Han Ruoling 
Published: June 2024

Abstract
Background
The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.

Methods
We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.

Results
Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s’) did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.

Conclusions
2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
Impact of perineal pain and delivery related factors on interference with activities of daily living until 1 month postpartum: A longitudinal prospective study
Authors: Yamada Akiko , Takahashi Yuki , Usami Yurika , Tamakoshi Koji 
Published: June 2024

Abstract
Background
Interference with activities of daily living can negatively impact maternal practices both physically and psychologically. This study aimed to explore the patterns of interference with activities of daily living and perineal pain among Japanese women until 1 month postpartum. Furthermore, we aimed to describe how both perineal pain and delivery-related factors were associated with interference with activities of daily living.

Methods
This study was part of a larger prospective longitudinal study conducted at five maternity hospitals in Japan. The participants were 293 women who had full-term vaginal deliveries and singleton infants. Participants self-evaluated their perineal pain and interference with activities of daily living using a 100 mm visual analogue scale and ‘behaviour that interferes with daily life scale’ at day 1, day 5, and 1 month postpartum. We used a linear mixed model to calculate the fixed-effects parameter estimates and their 95% confidence intervals. Interference with activities of daily living, which included difficulty sitting, difficulty moving, and difficulties with excretion and cleanliness, were set as the dependent variables.

Results
The final analysis included 184 participants with a mean age of 31.5±4.5 years. Perineal pain and the three sub-scales of interference with activities of daily living reduced from day 1 to 5 postpartum, and further from day 5 to 1 month postpartum (perineal pain, p<0.01, p<0.01; difficulty sitting, p<0.01, p<0.01; difficulty moving, p<0.01, p<0.01; difficulties with excretion and cleanliness, p<0.01, p<0.01). These tendencies did not change, even adjusted for independent variables using a mixed model. In the mixed model for follow-up data, perineal pain was a significantly and positively associated with three sub-scales of interference with activities of daily living, even after adjusted for perineal injury and episiotomy.

Conclusions
Positive relationships were observed between perineal pain and interference with activities of daily living until 1 month postpartum, although both reduced. To promote maternal role attainment through child-rearing since early postpartum, midwives should pay additional attention to mothers’ perineal pain as it could negatively affect their daily life and child-rearing.