bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue
Authors: Erevik Christine Bjørkvik , Kleiven Øyunn , Frøysa Vidar , Bjørkavoll-Bergseth Magnus , Chivulescu Monica , Klæboe Lars Gunnar , Dejgaard Lars , Auestad Bjørn , Skadberg Øyvind , Melberg Tor , Urheim Stig , Haugaa Kristina , Edvardsen Thor , Ørn Stein 
Published: January 2023

BackgroundThe effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue.Materials and methodsLV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress.Results59 healthy recreational athletes, 52 (43–59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p &lt; 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p &lt; 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003).ConclusionIncreased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.
Structural and electrophysiological determinants of atrial cardiomyopathy identify remodeling discrepancies between paroxysmal and persistent atrial fibrillation
Authors: Huang Taiyuan , Nairn Deborah , Chen Juan , Mueller-Edenborn Bjoern , Pilia Nicolas , Mayer Louisa , Eichenlaub Martin , Moreno-Weidmann Zoraida , Allgeier Juergen , Trenk Dietmar , Ahlgrim Christoph , Westermann Dirk , Arentz Thomas , Loewe Axel , Jadidi Amir 
Published: January 2023

BackgroundProgressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency.MethodsConsecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency.ResultsIn training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area &lt; 1.0 mV (threshold 4.55 cm2) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC &lt; 0.60 in identifying individuals with persistent AF in current study.ConclusionAmong 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.
A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer
Authors: Sawka Anna M. , Ghai Sangeet , Tomlinson George , Baxter Nancy N. , Corsten Martin , Imran Syed Ali , Bissada Eric , Lebouef Rebecca , Audet Nathalie , Brassard Maryse , Zhang Han , Gupta Michael , Nichols Anthony C. , Morrison Deric , Johnson-Obeski Stephanie , Prisman Eitan , Anderson Don , Chandarana Shamir P. , Ghaznavi Sana , Jones Jennifer , Gafni Amiram , Matelski John J. , Xu Wei , Goldstein David P. ,   the Canadian Thyroid Cancer Active Surveillance Study Group
Published: January 2023

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (&lt; 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.
The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study
Authors: Jiang Liying , Jiang Ying , Wang Anqi , Wu Cui , Shen Yi 
Published: January 2023

ObjectivesThe causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).MethodsIn this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.ResultsMR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn’t support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger).ConclusionsOur findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.
Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies
Authors: Wang Yining , Yu Liming , Ye Zhiqiang , Lin Rui , Sun Antonia RuJia , Liu Lingna , Wei Jinsong , Deng Feifu , Zhong Xiangxin , Cui Liao , Li Li , Liu Yanzhi 
Published: January 2023

AimsIncreasing evidence suggests that metformin can affect bone metabolism beyond its hypoglycemic effects in diabetic patients. However, the effects of metformin on fracture risk in type 2 diabetes mellitus (T2DM) patients remain unclear. A systematic review and meta-analysis were performed in this study to evaluate the association between metformin application and fracture risk in T2DM patients based on previous studies published until June 2021.MethodsA systematic search was performed to collect publications on metformin application in T2DM patients based on PubMed, Embase, Cochran, and Web of Science databases. Meta-analysis was performed by using a random-effects model to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). Subgroup analyses based on cohort/case-control and ethnicity and sensitivity analyses were also performed.ResultsEleven studies were included in the meta-analysis. Results demonstrated metformin use was not significantly associated with a decreased risk of fracture (RR, 0.91; 95% CI, 0.81–1.02; I2 = 96.8%). Moreover, metformin use also demonstrated similar results in subgroup analyses of seven cohort studies and four case-control studies, respectively (RR, 0.90; 95% CI, 0.76–1.07; I2 = 98.0%; RR, 0.96; 96% CI, 0.89–1.03; I2 = 53.7%). Sensitivity analysis revealed that there was no publication bias.ConclusionThere was no significant correlation between fracture risk and metformin application in T2DM patients. Due to a limited number of existing studies, further research is needed to make a definite conclusion for clinical consensus.
Study on characteristics of mooring system of a new floating offshore wind turbine in shallow water by experiment
Authors: Huo Fali , Xu Jie , Yang Hongkun , Yuan Zhaojun , Shen Zhongxiang 
Published: January 2023

At present, researches on floating offshore wind turbine are mainly focused on deep water areas beyond 50 m, and less research has been conducted for shallow water. Considering that the floating fan still has many application values in 30 m–50 m area, it is necessary to study the floating offshore wind turbine in shallow water area. With the shallow design water depth and the effect of topography, the environmental condition is complex. Therefore, it is relatively difficult to design the mooring system. In this paper, a multi-point mooring system is proposed which based on PivotBuoy, a floating offshore wind turbine designed by X1-Wind Company. The characteristics of motion responses of the floating offshore wind turbine and mooring force under different mooring cable schemes are studied by physical model experiment. Through these results, it can be found that when the mooring system adopts the hybrid mooring cable scheme (anchor chain + polymer cable + anchor chain), the pitch and heave motion responses of the floating offshore wind turbine will increase by about 30% maximally, the mooring cable tension will decrease by about 27%. This paper also studies the influence of water depth and mooring cable pretension on the mooring system under the hybrid mooring cable scheme, and the characteristics of mooring system in 22.5 m shallow water. These results can provide certain theoretical guidance for the design of mooring system of floating offshore wind turbine in shallow water.
Comprehensive evaluation and spatial-temporal differences analysis of China’s inter-provincial doing business environment based on Entropy-CoCoSo method
Authors: Zhu Yanmin , Zeng Shouzhen , Lin Zhisen , Ullah Kifayat 
Published: January 2023

Introduction: The Doing Business environment affects the operation of enterprises in the region and exerts an important impact on economic development, taxation, and employment.Methods: According to the characteristics of large differences in the level of economic development between provinces in China, this study builds a set of scientific and reasonable evaluation index systems of inter-provincial Doing Business environment, including five first-level indicators and 11 second-level indicators. Moreover, this study constructs a comprehensive evaluation model based on the Entropy-CoCoSo framework and explores its application in China’s inter-provincial Doing Business environment evaluation.Results: Based on China’s provincial panel data from 2007 to 2020, the research found that the Doing Business environment of each province has generally improved in recent years, but the inter-provincial differences are more prominent. The western provinces have obvious late-mover advantages.Discussion: Finally, we put forward several targeted suggestions, providing a powerful reference for optimizing China’s Doing Business environment and promoting high-quality economic development.
Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits
Authors: Chitre Apurva S. , Hebda-Bauer Elaine K. , Blandino Peter , Bimschleger Hannah , Nguyen Khai-Minh , Maras Pamela , Li Fei , Ozel A. Bilge , Pan Yanchao , Polesskaya Oksana , Cheng Riyan , Flagel Shelly B. , Watson Stanley J. , Li Jun , Akil Huda , Palmer Abraham A. 
Published: January 2023

Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability to these disorders. To model these heritable tendencies, we selectively bred rats for high and low exploration in a novel environment [bred High Responders (bHR) vs. Low Responders (bLR)]. To identify genes underlying the response to selection, we phenotyped and genotyped 538 rats from an F2 cross between bHR and bLR. Several behavioral traits show high heritability, including the selection trait: exploratory locomotion (EL) in a novel environment. There were significant phenotypic and genetic correlations between tests that capture facets of EL and anxiety. There were also correlations with Pavlovian conditioned approach (PavCA) behavior despite the lower heritability of that trait. Ten significant and conditionally independent loci for six behavioral traits were identified. Five of the six traits reflect different facets of EL that were captured by three behavioral tests. Distance traveled measures from the open field and the elevated plus maze map onto different loci, thus may represent different aspects of novelty-induced locomotor activity. The sixth behavioral trait, number of fecal boli, is the only anxiety-related trait mapping to a significant locus on chromosome 18 within which the Pik3c3 gene is located. There were no significant loci for PavCA. We identified a missense variant in the Plekhf1 gene on the chromosome 1:95 Mb QTL and Fancf and Gas2 as potential candidate genes that may drive the chromosome 1:107 Mb QTL for EL traits. The identification of a locomotor activity-related QTL on chromosome 7 encompassing the Pkhd1l1 and Trhr genes is consistent with our previous finding of these genes being differentially expressed in the hippocampus of bHR vs. bLR rats. The strong heritability coupled with identification of several loci associated with exploratory locomotion and emotionality provide compelling support for this selectively bred rat model in discovering relatively large effect causal variants tied to elements of internalizing and externalizing behaviors inherent to psychiatric and substance use disorders.
Genome-wide DNA methylation profiling in chronic lymphocytic leukaemia
Authors: Zhang Qiuyi , Gao Ying , Lin Shuchun , Goldin Lynn R. , Wang Yonghong , Stevenson Holly , Edelman Daniel C. , Killian Keith , Marti Gerald , Meltzer Paul S. , Xiang Song , Caporaso Neil E. 
Published: January 2023

Background:DNA methylation aberrations are widespread among the malignant B lymphocytes of patients with chronic lymphocytic leukaemia (CLL), suggesting that DNA methylation might contribute to the pathogenesis of CLL.Aim:We aimed to explore the differentially methylated positions (DMPs) associated with CLL and screen the differentially methylated and expressed genes (DMEGs) by combining public databases. We aimed to observe the direction of each DMEG in CLL based on the DMPs in the promoter and the body region respectively to narrow down DMEGs. We also aimed to explore the methylation heterogeneity of CLL subgroups and the effect of B cells maturation on CLL.Methods:In this population-based case control study, we reported a genome-wide DNA methylation association study using the Infinium HumanMethylation450 BeadChip, profiling the DNA methylation of CD19+B Cells from 48 CLL cases and 28 healthy controls. By integrating methylation data and expression data from public databases, gene sets were jointly screened, and then the relationship between methylation sites in promoter and body region and expression of each gene was explored. In addition, support vector machine (SVM) classification algorithm was used to identify subgroups of CLL cases based on methylation pattern, and the effect of B-cell differentiation related methylation sites on CLL-related sites was observed.Results:We identified 34,797 DMPs related to CLL across the genome, most of which were hypomethylated; the majority were located in gene body regions. By combining these DMPs with published DNA methylation and RNA sequencing data, we detected 26,244 replicated DMPs associated with 1,130 genes whose expression were significantly different in CLL cases. Among these DMEGs, nine low expressed DMEGs were selected with hypermethylated in promoter and hypomethylated in body region, and 83 high expressed DMEGs were selected with both hypomethylated in promoter and body region. The 48 CLL cases were divided into 3 subgroups based on methylation site by SVM algorithm. Over 92% of CpGs associated with B cell subtypes were found in CLL-related DMPs.Conclusion:The DNA methylation pattern was altered across the genome in CLL patients. The methylation ofZAP70,FMOD, andADAMTS17was significantly different between CLL cases and controls. Further studies are warranted to confirm our findings and identify the underlying mechanisms through which these methylation markers are associated with CLL.
Unraveling signatures of chicken genetic diversity and divergent selection in breed-specific patterns of early myogenesis, nitric oxide metabolism and post-hatch growth
Authors: Kochish Ivan I. , Titov Vladimir Yu. , Nikonov Ilya N. , Brazhnik Evgeni A. , Vorobyov Nikolai I. , Korenyuga Maxim V. , Myasnikova Olga V. , Dolgorukova Anna M. , Griffin Darren K. , Romanov Michael N. 
Published: January 2023

Introduction: Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR).Methods: These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (MSTN, GHR, MEF2C, MYOD1, MYOG, MYH1, and MYF5), quantitative real-time PCR was used.Results: We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated (“accord”) expression patterns of MSTN, GHR, and MEFC2 were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for MYOG and MYOD1 in the breast muscles and for MYOG and MYF5 genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds.Discussion: The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.