bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Serum Uromodulin and Its Genetic Variants With Blood Pressure and Hypertension in Chinese Adults
Authors: Wang Yang , Du Ming-Fei , Yao Shi , Zou Ting , Zhang Xiao-Yu , Hu Gui-Lin , Chu Chao , Liao Yue-Yuan , Chen Chen , Wang Dan , Ma Qiong , Wang Ke-Ke , Sun Yue , Niu Ze-Jiaxin , Yan Rui-Chen , Yan Yu , Zhou Hao-Wei , Jia Hao , Gao Wei-Hua , Li Hao , Li Chun-Hua , Chen Fang-Yao , Gao Ke , Zhang Jie , Safirstein Robert , Wang Feng , Yang Tie-Lin , Mu Jian-Jun 
Published: November 2021

Background: Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk.Methods: A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension.Results: SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1 vs. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension [0.978 (0.972–0.984)] in Hanzhong Adolescent Hypertension Study cohort.Conclusion: This study shows that uromodulin is associated with blood pressure progression and development of hypertension.
Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification
Authors: Zhu Yingyin , Zhong Wanling , Peng Jing , Wu Huichao , Du Shouying 
Published: November 2021

Purpose: The external preparation of the Tibetan medicine formula, Baimai ointment (BMO), has great therapeutic effects on osteoarthritis (OA). However, its molecular mechanism remains almost elusive. Here, a comprehensive strategy combining network pharmacology and molecular docking with pharmacological experiments was adopted to reveal the molecular mechanism of BMO against OA.Methods: The traditional Chinese medicine for systems pharmacology (TCMSP) database and analysis platform, traditional Chinese medicine integrated database (TCMID), GeneCards database, and DisGeNET database were used to screen the active components and targets of BMO in treating OA. A component–target (C-T) network was built with the help of Cytoscape, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment through STRING. Autodock Tools which was used to dock the key components and key target proteins was analyzed. Animal experiments were performed to verify the key targets of BMO. Hematoxylin–eosin and toluidine blue staining were used to observe the pathology of joints. Protein expression was determined using enzyme-linked immunosorbent assay.Results: Bioactive compounds and targets of BMO and OA were screened. The network analysis revealed that 17-β-estradiol, curcumin, licochalone A, quercetin, and glycyrrhizic acid were the candidate key components, and IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B were the candidate key targets in treating OA. The KEGG indicated that the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway were the potential pathways. Molecular docking implied a strong combination between key components and key targets. The pathology and animal experiments showed BMO had great effects on OA via regulating IL6, TNF, MAPK1, VEGFA, CXCL8, and IL1B targets. These findings were consistent with the results obtained from the network pharmacology approach.Conclusion: This study preliminarily illustrated the candidate key components, key targets, and potential pathways of BMO against OA. It also provided a promising method to study the Tibetan medicine formula or external preparations.
Metabolomic Profiles of Plasma Retinol-Associated Dyslipidemia in Men and Women
Authors: Wang Ninglin , Ru Yuan , Yang Zhiying , Sun Changxuan , Li Shanshan , Min Yan , Zhao Xueyin , Lu Ying , Hsing Ann W. , Zhu Shankuan 
Published: November 2021

Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population.Methods: We included 250 participants aged 20–80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex.Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status.Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).
Diagnosis of Breast Cancer Using Radiomics Models Built Based on Dynamic Contrast Enhanced MRI Combined With Mammography
Authors: Zhao You-Fan , Chen Zhongwei , Zhang Yang , Zhou Jiejie , Chen Jeon-Hor , Lee Kyoung Eun , Combs Freddie J. , Parajuli Ritesh , Mehta Rita S. , Wang Meihao , Su Min-Ying 
Published: November 2021

ObjectiveTo build radiomics models using features extracted from DCE-MRI and mammography for diagnosis of breast cancer.Materials and Methods266 patients receiving MRI and mammography, who had well-enhanced lesions on MRI and histologically confirmed diagnosis were analyzed. Training dataset had 146 malignant and 56 benign, and testing dataset had 48 malignant and 18 benign lesions. Fuzzy-C-means clustering algorithm was used to segment the enhanced lesion on subtraction MRI maps. Two radiologists manually outlined the corresponding lesion on mammography by consensus, with the guidance of MRI maximum intensity projection. Features were extracted using PyRadiomics from three DCE-MRI parametric maps, and from the lesion and a 2-cm bandshell margin on mammography. The support vector machine (SVM) was applied for feature selection and model building, using 5 datasets: DCE-MRI, mammography lesion-ROI, mammography margin-ROI, mammography lesion+margin, and all combined.ResultsIn the training dataset evaluated using 10-fold cross-validation, the diagnostic accuracy of the individual model was 83.2% for DCE-MRI, 75.7% for mammography lesion, 64.4% for mammography margin, and 77.2% for lesion+margin. When all features were combined, the accuracy was improved to 89.6%. By adding mammography features to MRI, the specificity was significantly improved from 69.6% (39/56) to 82.1% (46/56), p&lt;0.01. When the developed models were applied to the independent testing dataset, the accuracy was 78.8% for DCE-MRI and 83.3% for combined MRI+Mammography.ConclusionThe radiomics model built from the combined MRI and mammography has the potential to provide a machine learning-based diagnostic tool and decrease the false positive diagnosis of contrast-enhanced benign lesions on MRI.
Dorsal Root Entry Zone Lesioning for Brachial Plexus Avulsion Injuries: Case Series and Literature Review
Authors: Chalil Alan , Wang Qian , Abbass Mohamad , Santyr Brendan G. , MacDougall Keith W. , Staudt Michael D. 
Published: November 2021

Introduction: Brachial plexus avulsion (BPA) injuries commonly occur secondary to motor vehicle collisions, usually in the young adult population. These injuries are associated with significant morbidity, and up to 90% of patients suffer from deafferentation pain. Neuromodulation procedures can be efficacious in the treatment of refractory neuropathic pain, although the treatment of pain due to BPA can be challenging. Dorsal root entry zone (DREZ) lesioning is a classical and effective neurosurgical technique which has become underutilized in treating refractory root avulsion pain.Methods: A systematic review of the different technical nuances, procedural efficacy, and complication profiles regarding DREZ lesioning for BPA injuries in the literature is included. We also present an institutional case series of 7 patients with BPA injuries who underwent DREZ lesioning.Results: In the literature, 692 patients were identified to have undergone DREZ lesioning for pain related to BPA. In 567 patients, the surgery was successful in reducing pain intensity by over 50% in comparison to baseline (81.9%). Complications included transient motor deficits (11%) and transient sensory deficits (11%). Other complications including permanent disability, cardiovascular complications, infections, or death were rare (&lt;1.9%). In our case series, all but one patient achieved &gt;50% reduction in pain intensity, with the mean pre-operative pain of 7.9 ± 0.63 (visual analog scale) reduced to 2.1 ± 0.99 at last follow-up (p &lt; 0.01).Conclusion: Both the literature and the current case series demonstrate excellent pain severity reduction following DREZ ablation for deafferentation pain secondary to BPA.
Comparison of Five Prophylactically Intravenous Drugs in Preventing Opioid-Induced Cough: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Authors: Dong Yunxia , Chang Xiaohan 
Published: November 2021

Background: Due to the absence of direct comparisons of different therapeutic drugs in preventing opioid-induced cough (OIC) during the induction of general anesthesia, clinicians often faced difficulties in choosing the optimal drug for these patients. Hence, this network meta-analysis was conducted to solve this problem.Methods: Online databases, including Pubmed, Embase, Web of Science, Cochrane, and Google Scholar, were searched comprehensively to identify eligible randomized controlled trials (RCTs), up to March 15th, 2021. Within a Bayesian framework, network meta-analysis was performed by the “gemtc” version 0.8.2 package of R-3.4.0 software, and a pooled risk ratio (RR) associated with 95% credible interval (CrI) was calculated.Results: A total of 20 RCTs were finally enrolled, and the overall heterogeneity for this study was low to moderate. Traditional pair-wise meta-analysis results indicated that all of the five drugs, namely, lidocaine, ketamine, dezocine, butorphanol, and dexmedetomidine could prevent OIC for four clinical outcomes, compared with the placebo (all p-values &lt; 0.05). Moreover, dezocine had the best effect, compared with that of the other drugs (all p-values &lt; 0.05). Network meta-analysis results suggested that the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine based on individual/cumulative rank plots and surface under the cumulative ranking curve (SUCRA) probabilities. The node-splitting method indicated the consistency of the direct and indirect evidence.Conclusions: Our results indicated that all of these five drugs could prevent OIC compared with the placebo. Moreover, the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine. Our results were anticipated to provide references for guiding clinical research, and further high-quality RCTs were required to verify our findings.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021243358].
Knockout of AMPKα2 Blocked the Protection of Sestrin2 Overexpression Against Cardiac Hypertrophy Induced by Pressure Overload
Authors: Zhang Nan , Liao Hai-Han , Feng Hong , Mou Shan-Qi , Li Wen-Jing , Aiyasiding Xiahenazi , Lin Zheng , Ding Wen , Zhou Zi-Ying , Yan Han , Chen Si , Tang Qi-Zhu 
Published: November 2021

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2.Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60–70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout.Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.
The Implementation of a Primary Care-Based Integrated Mobile Health Intervention for Stroke Management in Rural China: Mixed-Methods Process Evaluation
Authors: Gong Enying , Sun Lixin , Long Qian , Xu Hanzhang , Gu Wanbing , Bettger Janet Prvu , Tan Jingru , Ma Jixiang , Jafar Tazeen Hasan , Oldenburg Brian , Yan Lijing L. 
Published: November 2021

Background: There is a lack of evidence concerning the effective implementation of strategies for stroke prevention and management, particularly in resource-limited settings. A primary-care-based integrated mobile health intervention (SINEMA intervention) has been implemented and evaluated via a 1-year-long cluster-randomized controlled trial. This study reports the findings from the trial implementation and process evaluation that investigate the implementation of the intervention and inform factors that may influence the wider implementation of the intervention in the future.Methods: We developed an evaluation framework by employing both the RE-AIM framework and the MRC process evaluation framework to describe the implementation indicators, related enablers and barriers, and illustrate some potential impact pathways that may influence the effectiveness of the intervention in the trial. Quantitative data were collected from surveys and extracted from digital health monitoring systems. In addition, we conducted quarterly in-depth interviews with stakeholders in order to understand barriers and enablers of program implementation and effectiveness. Quantitative data analysis and thematic qualitative data analysis were applied, and the findings were synthesized based on the evaluation framework.Results: The SINEMA intervention was successfully implemented in 25 rural villages, reached 637 patients with stroke in rural Northern China during the 12 months of the trial. Almost 90% of the participants received all follow-up visits per protocol, and about half of the participants received daily voice messages. The majority of the intervention components were adopted by village doctors with some adaptation made. The interaction between human-delivered and technology-enabled components reinforced the program implementation and effectiveness. However, characteristics of the participants, doctor-patient relationships, and the healthcare system context attributed to the variation of program implementation and effectiveness.Conclusion: A comprehensive evaluation of program implementation demonstrates that the SINEMA program was well implemented in rural China. Findings from this research provide additional information for program adaptation, which shed light on the future program scale-up. The study also demonstrates the feasibility of combining RE-AIM and MRC process evaluation frameworks in process and implementation evaluation in trials.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03185858.
Effect of Microvascular Invasion on the Prognosis in Hepatocellular Carcinoma and Analysis of Related Risk Factors: A Two-Center Study
Authors: Yanhan Wang , Lianfang Lu , Hao Liu , Yunfeng Ding , Nannan Song , Fanfan Lin , Chengzhan Zhu , Meilong Wu , Chuandong Sun 
Published: November 2021

Objective: Microvascular invasion is considered to initiate intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). We aimed to analyze the effect of MVI on the prognosis in HCC and identify related risk factors for microvascular invasion (MVI).Methods: The clinical data of 553 HCC patients who underwent liver surgery at Qingdao University from January 2014 to December 2018 and 89 patients at Beijing Tsinghua Changgung Hospital treated between October 2014 and October 2019 were collected retrospectively. We explored the impact of MVI on the prognosis of patients with HCC using Kaplan-Meier analysis. We conducted logistic regression analysis to identify variables significantly related to MVI.Results: Pathological examination confirmed the presence of MVI in 265 patients (41.3%). Six factors independently correlated with MVI were incorporated into the multivariate logistic regression analysis: Edmondson-Steiner grade [odds ratio (OR) = 3.244, 95%CI: 2.243–4.692; p &lt; 0.001], liver capsule invasion (OR = 1.755; 95%CI: 1.215–2.535; p = 0.003), bile duct tumor thrombi (OR = 20.926; 95%CI: 2.552–171.553; p = 0.005), α-fetoprotein (&gt; 400 vs. &lt; 400 ng/ml; OR = 1.530; 95%CI: 1.017–2.303; p = 0.041), tumor size (OR = 1.095; 95%CI: 1.027–1.166; p = 0.005), and neutrophil-lymphocyte ratio (OR = 1.086; 95%CI: 1.016–1.162; p = 0.015). The area under the receiver operating characteristic curve (AUC) was 0.743 (95%CI: 0.704–0.781; p &lt; 0.001), indicating that our logistic regression model had significant clinical usefulness.Conclusions: We analyzed the effect of MVI on the prognosis in HCC and evaluated the risk factors for MVI, which could be helpful in making decisions regarding patients with a high risk of recurrence.
La influencia del neoconstitucionalismo en la construcción del precedente judicial en el derecho colombiano
Authors: Páez Quiñones Jorge Andrés 
Published: November 2021

El presente artículo describe y reflexiona sobre el origen y concepto del neoconstitucionalismo en Colombia, para esto se hará una revisión doctrinal y jurisprudencial, buscando delimitar el alcance y consecuencias de esta teoría en nuestro ordenamiento jurídico. También se hace énfasis en la construcción del precedente judicial a la luz de la constitucionalización del derecho, generando un puente crítico que permita al lector entender cómo, por medio de este trasplante jurídico, la Corte Constitucional tomó elementos conceptuales para la interpretación de la Constitución de 1991.
Cause analysis of width-dependence of on-current variability in thin gate-all-around silicon nanowire MOSFET
Authors: Liu Zihao , Mizutani Tomoko , Saraya Takuya , Kobayashi Masaharu , Hiramoto Toshiro 
Published: November 2021

Abstract
In this study, the width dependence of on-current variability in extremely narrow gate-all-around silicon nanowire MOSFET down to 2 nm width is analyzed by variability decomposition into components as well as analyzing the Pelgrom plot. It is found that the current variability rapidly increases below 4 nm mainly due to quantum-effect-induced threshold voltage variability and silicon-thickness-fluctuation-induced mobility fluctuation. The current variability becomes even worse in 2 nm, which is fundamentally caused by line width roughness.
A novel 1T2R self-reference physically unclonable function suitable for advanced logic nodes for high security level applications
Authors: Lin Yu-Hsuan , Lee Dai-Ying , Lee Ming-Hsiu , Tseng Po-Hao , Chen Wei-Chen , Hsieh Kuang-Yeu , Wang Keh-Chung , Lu Chih-Yuan 
Published: November 2021

Abstract
A self-reference resistive random-access memory (ReRAM)-based one-transistor, two-ReRAM (1T2R) physically unclonable function (PUF) is proposed to provide a hardware security feature for electrical products in the IoT/5G era. There are four advantages from the proposed structure: (1) a small cell size; (2) intrinsic randomness; (3) no programming circuit; and (4) no data retention concerns. The conduction mechanism, temperature dependency, and read fluctuation of the pristine ReRAM device are studied. An information–address separation scheme is proposed which not only reduces the impact of the read noise and the temperature effect, but also improves system integrity against hardware attacks. The proposed 1T2R PUF unit also has great potential for use as a random seed for linear-feedback shift registers in pseudo random number generators with high unpredictability, good randomness, and a high data rate.