bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK1/2 Inhibitor Baricitinib Improves Skin Fibrosis and Digital Ulcers in Systemic Sclerosis
Authors: Hou Zhanying , Su Xuehan , Han Guangming , Xue Ruzeng , Chen Yangxia , Chen Ye , Wang Huan , Yang Bin , Liang Yunsheng , Ji Suyun 
Published: June 2022

BackgroundSystemic sclerosis (SSc) is a rare disabling connective tissue disease with few available treatment options. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality. A previous experiment has shown that JAK2 inhibitor can significantly improve skin fibrosis in bleomycin (BLM)-induced murine model, including reducing dermal thickening and collagen accumulation. We aimed to describe the efficacy of oral JAK1/2 inhibitor baricitinib in SSc patients, especially focusing on skin fibrosis and microvascular manifestations.MethodsWe described the different effects of oral selective JAK1, JAK2, or JAK3 inhibitor treatment in a BLM-induced skin fibrosis mouse model. Furthermore, 10 adult patients with dcSSc were treated with baricitinib. We assessed the changes in modified rodman skin score (mRSS) and digital ulcer net burden at week 12 and 24 from baseline. We also compared the absolute changes in scores on the Scleroderma Health Assessment Questionnaire (SHAQ) and a total score on the St. George's Respiratory Questionnaire (SGRQ) over a 24-week period.ResultsIn the experimental mouse model of skin fibrosis, a JAK1 and JAK2 inhibitor ameliorated skin fibrosis, and a JAK2 inhibitor had the most obvious effect. Treatment with the JAK2 inhibitor also blunted the capillary rarefaction. We demonstrated that skin fibrosis and digital ulcers were significantly relieved in 10 SSc patients treated with baricitinib. The mRSS significantly improved at week 12 from baseline, with a mean change in mRSS of −8.3 [95% confidence interval (CI), −12.03 to −4.574; p = 0.0007] and improved greater at week 24 to −11.67 (95% CI, −16.84 to −6.496; p = 0.0008). Among the four patients with digital ulcers (DU), three were completely healed at week 24, the number of ulcers in another patient was significantly reduced, and there was no patient with new ulcers. Only one adverse event (AE) of herpes zoster was observed.ConclusionsOur results indicate that selective JAK1 and JAK2 inhibitor alleviates skin fibrosis, and oral JAK1/2 inhibitor baricitinib is a potentially effective treatment for dcSSc patients with skin fibrosis and DU. Baricitinib was well-tolerated by most patients in this study. Additional large clinical trials are needed to confirm our pilot findings.Chinese Clinical Trial Registry NumberChiCTR2000030995.
Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice
Authors: Wang Lixin , Yuan Pu-Qing , Challis Collin , Ravindra Kumar Sripriya , Taché Yvette 
Published: June 2022

Systemic delivery of adeno-associated virus (AAV) vectors transduces the enteric nervous system. However, less is known on the mapping and morphological and neurochemical characterization in the adult mouse colon. We used AAV9-CAG-GFP (AAV9) and AAV-PHP.S-hSyn1-tdTomato farnesylated (PHP.S-tdTf) to investigate the segmental distribution, morphologies and neurochemical coding of the transduction. The vectors were retro-orbitally injected in male and female adult mice, and 3 weeks later, the colon was prepared for microcopy with or without immunohistochemistry for neuronal and non-neuronal markers. In contrast to the distributions in neonatal and juvenile rodents, the AAV transduction in neurons and/or nerve fibers was the highest in the proximal colon, decreased gradually in the transverse, and was sparse in the distal colon without difference between sexes. In the proximal colon, the AAV9-transduced myenteric neurons were unevenly distributed. The majority of enteric neurons did not have AAV9 expression in their processes, except those with big soma with or without variously shaped dendrites, and a long axon. Immunolabeling demonstrated that about 31% neurons were transduced by AAV9, and the transduction was in 50, 28, and 31% of cholinergic, nitrergic, and calbindin-positive myenteric neurons, respectively. The nerve fiber markers, calcitonin gene-related peptide alpha, tyrosine hydroxylase or vasoactive intestinal polypeptide co-localized with AAV9 or PHP.S-tdTf in the mucosa, and rarely in the myenteric plexus. Unexpectedly, AAV9 expression appeared also in a few c-Kit immunoreactive cells among the heavily populated interstitial cells of Cajal (ICC). In the distal colon, the AAV transduction appeared in a few nerve fibers mostly the interganglionic strands. Other types of AAV9 and AAV-PHP vectors induced a similar colonic segmental difference which is not colon specific since neurons were transduced in the small intestine and gastric antrum, while little in the gastric corpus and none in the lower esophagus.ConclusionThese findings demonstrate that in adult mice colon that there is a rostro-caudal decrease in the transduction of systemic delivery of AAV9 and its variants independent of sex. The characterization of AAV transduction in the proximal colon in cholinergic and nitrergic myenteric neurons along with a few ICC suggests implications in circuitries regulating motility.
Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings
Authors: Clemson Philip T. , Hoag Jeffrey B. , Cooke William H. , Eckberg Dwain L. , Stefanovska Aneta 
Published: June 2022

For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO2, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p &lt; 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145–0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation.
Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Liu Lin , Chen Jie , Liu Chang , Luo Yuxuan , Chen Jiayun , Fu Yuanyuan , Xu Yajie , Wu Haili , Li Xue , Wang Hui 
Published: June 2022

IntroductionHeavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically.MethodsWe searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included.ResultsIn all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); −1.40 (−1.96, −0.85); −2.26 (−3.39, −1.13); p = 0.01, 0.0003, 0.04, &lt;0.0001, &lt;0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); −1.53 (−2.28, −0.78); −2.40 (−3.69, −1.10); p = 0.002, 0.0003, &lt;0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): −2.12 (−3.55, −0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed.ConclusionFor BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934, identifier: CRD42020176934.
The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
Authors: Yan Miaolong , Wu Jiayuan , Xue Min , Mo Juanfen , Zheng Li , Zhang Jun , Gao Zhenzhen , Bao Yi 
Published: June 2022

ObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.MethodsPathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.ResultsKaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P&lt;0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P&lt;0.05). The MTHFR C667T genotype (χ2 = 7.987, P=0.018) and allele distribution (χ2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 =0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).ConclusionsThe Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.
Preoperative Prediction of Inferior Vena Cava Wall Invasion of Tumor Thrombus in Renal Cell Carcinoma: Radiomics Models Based on Magnetic Resonance Imaging
Authors: Sun Zhaonan , Cui Yingpu , Xu Chunru , Yu Yanfei , Han Chao , Liu Xiang , Lin Zhiyong , Wang Xiangpeng , Li Changxin , Zhang Xiaodong , Wang Xiaoying 
Published: June 2022

ObjectiveTo develop radiomics models to predict inferior vena cava (IVC) wall invasion by tumor thrombus (TT) in patients with renal cell carcinoma (RCC).MethodsPreoperative MR images were retrospectively collected from 91 patients with RCC who underwent radical nephrectomy (RN) and thrombectomy. The images were randomly allocated into a training (n = 64) and validation (n = 27) cohort. The inter-and intra-rater agreements were organized to compare masks delineated by two radiologists. The masks of TT and IVC were manually annotated on axial fat-suppression T2-weighted images (fsT2WI) by one radiologist. The following models were trained to predict the probability of IVC wall invasion: two radiomics models using radiomics features extracted from the two masks (model 1, radiomics model_IVC; model 2, radiomics model_TT), two combined models using radiomics features and radiological features (model 3, combined model_IVC; model 4, combined model_TT), and one radiological model (model 5) using radiological features. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were applied to validate the discriminatory effect and clinical benefit of the models.ResultsModel 1 to model 5 yielded area under the curves (AUCs) of 0.881, 0.857, 0.883, 0.889, and 0.769, respectively, in the validation cohort. No significant differences were found between these models (p = 0.108-0.951). The dicision curve analysis (DCA) showed that the model 3 had a higher overall net benefit than the model 1, model 2, model 4, and model 5.ConclusionsThe combined model_IVC (model 3) based on axial fsT2WI exhibited excellent predictive performance in predicting IVC wall invasion status.
Real-Life Experience of Regorafenib in Patients With Advanced Hepatocellular Carcinoma
Authors: Hou Jing-Yu , Xiao Ya-ting , Huang Jing-Bo , Jiang Xin-Hua , Jiang Kai , Li Xun , Xu Li , Chen Min-Shan 
Published: June 2022

Background: The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice.Objective: We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC.Patients and Methods: A total of 41 patients with advanced HCC who did not respond to sorafenib and followed a regorafenib regimen were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), radiological responses, and adverse events (AEs) were evaluated. Survival curves were compared by using the log-rank test and constructed with the Kaplan–Meier method.Results: The median PFS with regorafenib was 6.6 months (range: 5.0–8.2 months), and the median OS with regorafenib was not reached. The 1-year OS rate of regorafenib was 66.4%. The median OS of sequential sorafenib to regorafenib treatment was 35.3 months [95% confidence interval (CI), 24.3–46.3], and the 2-year OS rate of sequential sorafenib to regorafenib treatment was 74.4%. The most common AEs of regorafenib treatment were elevated aspartate aminotransferase [17/41 patients (41.5%)], elevated alanine aminotransferase [16/41 patients (39%)] and hand-foot syndrome [14/41 patients (34.1%)].Conclusion: Regorafenib appears to be safe and clinically effective in patients with advanced HCC who progressed on first-line sorafenib.
Effect of Core Training on Skill Performance Among Athletes: A Systematic Review
Authors: Luo Shengyao , Soh Kim Geok , Soh Kim Lam , Sun He , Nasiruddin Nasnoor Juzaily Mohd , Du Congxin , Zhai Xiuwen 
Published: June 2022

Background:This study aims to present a critical review of the existing literature on the effect of core training on athletes’ skill performance, and to provide recommendations and suggest future research directions for both coaches and researchers.Methods:The data in this study were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We collected studies in the literature using prominent academic and scientific databases such as Ebscohost, Scopus, PubMed, Web of Science, and Google Scholar. Only 16 of the 119 studies met all of the inclusion criteria, and were thus included in the systematic review. Each study’s quality was determined using the PEDro scale. The scoring of 16 studies ranges from 2 to 5.Results:Core training could potentially improve skill performance among football, handball, basketball, swimming, dancing, Karate, Muay Thai, gymnasts, volleyball, badminton, and golf players.Conclusion:Compared with the traditional training methods, core training is a new strength training method. Strong core muscles function as hubs in the biological motor chain, which create a fulcrum for the four limbs’ strength and establish a channel for the cohesion, transmission, and integration of the upper and lower limbs. In other words, core training optimizes the transfer and overall control of motion and force to the terminal segment within athletic actions. Meanwhile, core training could increase stability and stiffness in the spine to reduce unrequired “energy leaks” and torso movement during the exertion of external loads. This mechanism could help athletes achieve better skill performance. Therefore, this review suggests that core training should be considered integrated into athletes’ daily training routines.Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100013].
Viral Anxiety Mediates the Influence of Intolerance of Uncertainty on Adherence to Physical Distancing Among Healthcare Workers in COVID-19 Pandemic
Authors: Chung Seockhoon , Lee Taeyeop , Hong Youjin , Ahmed Oli , Silva Washington Allysson Dantas , Gouin Jean-Philippe 
Published: June 2022

IntroductionThe aims of this study were to examine the mediation effect of viral anxiety of healthcare workers on the influence of their intolerance of uncertainty on the adherence to physical distancing during the COVID-19 pandemic.MethodsAn online survey was conducted among 329 healthcare workers (female: 81.4%, nursing professionals: 59.0%, and shift workers: 22.3%) on November 29, 2021. Participants responded to questionnaires on adherence to physical distancing, health beliefs, and perceived social norms, and rating scales of the Stress and Anxiety to Viral Epidemics-6 items (SAVE-6), Patient Health Questionnaire-9 items (PHQ-9), and the Intolerance of Uncertainty-12 items (IUS-12) scale.ResultsAdherence to physical distancing of healthcare workers was predicted by perceived benefits of physical distancing (β = 0.13, p = 0.01), personal injunctive norms (β = 0.32, p &lt; 0.001), SAVE-6 score (β = 0.13, p = 0.02), and IUS-12 score (β = 0.10, p = 0.045) (adjusted R2 = 0.21, F = 22.3, p &lt; 0.001). Viral anxiety mediated the association between intolerance of uncertainty and adherence to physical distancing but not the influence of perceived benefits and personal injunctive norms on adherence to physical distancing.ConclusionWe observed that viral anxiety of healthcare workers mediated the association between intolerance of uncertainty and adherence to physical distancing. During this pandemic, exploring adherence to physical distancing and its predicting factors will be helpful for the safety of healthcare workers and the patients for whom they care.
Family Socioeconomic Position and Lung Cancer Risk: A Meta-Analysis and a Mendelian Randomization Study
Authors: Zou Xusen , Wang Runchen , Yang Zhao , Wang Qixia , Fu Wenhai , Huo Zhenyu , Ge Fan , Zhong Ran , Jiang Yu , Li Jiangfu , Xiong Shan , Hong Wen , Liang Wenhua 
Published: June 2022

BackgroundFamily socioeconomic position (SEP) in childhood is an important factor to predict some chronic diseases. However, the association between family SEP in childhood and the risk of lung cancer is not clear.MethodsA systematic search was performed to explore their relationship. We selected education level, socioeconomic positions of parents and childhood housing conditions to represent an individual family SEP. Hazard ratios (HRs) of lung cancer specific-mortality were synthesized using a random effects model. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SEP to assess the possible causal relationship of SEP and risk of lung cancer.ResultsThrough meta-analysis of 13 studies, we observed that to compared with the better SEP, the poorer SEP in the childhood was associated with the increased lung cancer risk in the adulthood (HR: 1.25, 95% CI: 1.10 to 1.43). In addition, the dose-response analysis revealed a positive correlation between the poorer SEP and increased lung cancer risk. Same conclusion was reached in MR [(education level) OR 0.50, 95% CI: 0.39 to 0.63; P &lt; 0.001].ConclusionThis study indicates that poor family socioeconomic position in childhood is causally correlated with lung cancer risk in adulthood.Systematic Review Registrationidentifier: 159082.