bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth Weight and Adult Obesity Index in Relation to the Risk of Hypertension: A Prospective Cohort Study in the UK Biobank
Authors: Zhang Yi , Liang Jingjia , Liu Qian , Fan Xikang , Xu Cheng , Gu Aihua , Zhao Wei , Hang Dong 
Published: June 2021

Objectives: To investigate the association between birth weight and the risk of hypertension, and to examine the interaction between birth weight and the adult obesity index.Methods: We included 199,893 participants who had birth weight data and no history of hypertension at baseline (2006–2010) from the UK Biobank. A multivariate cubic regression spline was used to visually explore the dose-response relationship. Multivariate Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We observed a nonlinear inverse association between birth weight and hypertension. The risk for hypertension decreased as birth weight increased up to approximately 3.80 kg. Compared with the participants with the fourth quintile of birth weight (3.43–3.80 kg), those with the first quartile of birth weight (&lt;2.88 kg) were associated with a 25% higher risk of hypertension [HR 1.25; 95% CI (1.18–1.32)]. In addition, the participants with birth weight &lt;2.88 kg and body mass index ≥30 kg/m2 had the highest risk [HR 3.54; 95% CI (3.16–3.97); p for interaction &lt;0.0001], as compared with those with birth weight between 3.43–3.80 kg and body mass index between 18.5–25.0 kg/m2. These associations were largely consistent in the stratified and sensitivity analyses.Conclusion: Our findings indicate that lower birth weight is nonlinearly correlated with higher risk of hypertension, and birth weight between 3.43–3.80 kg might represent an intervention threshold. Moreover, lower birth weight may interact with adult obesity to significantly increase hypertension risk.
Acetazolamide Improves Right Ventricular Function and Metabolic Gene Dysregulation in Experimental Pulmonary Arterial Hypertension
Authors: Spyropoulos Fotios , Michael Zoe , Finander Benjamin , Vitali Sally , Kosmas Kosmas , Zymaris Panagiotis , Kalish Brian T. , Kourembanas Stella , Christou Helen 
Published: June 2021

Background: Right ventricular (RV) performance is a key determinant of mortality in pulmonary arterial hypertension (PAH). RV failure is characterized by metabolic dysregulation with unbalanced anaerobic glycolysis, oxidative phosphorylation, and fatty acid oxidation (FAO). We previously found that acetazolamide (ACTZ) treatment modulates the pulmonary inflammatory response and ameliorates experimental PAH.Objective: To evaluate the effect of ACTZ treatment on RV function and metabolic profile in experimental PAH.Design/Methods: In the Sugen 5416/hypoxia (SuHx) rat model of severe PAH, RV transcriptomic analysis was performed by RNA-seq, and top metabolic targets were validated by RT-PCR. We assessed the effect of therapeutic administration of ACTZ in the drinking water on hemodynamics by catheterization [right and left ventricular systolic pressure (RVSP and LVSP, respectively)] and echocardiography [pulmonary artery acceleration time (PAAT), RV wall thickness in diastole (RVWT), RV end-diastolic diameter (RVEDD), tricuspid annular plane systolic excursion (TAPSE)] and on RV hypertrophy (RVH) by Fulton's index (FI) and RV-to-body weight (BW) ratio (RV/BW). We also examined myocardial histopathology and expression of metabolic markers in RV tissues.Results: There was a distinct transcriptomic signature of RVH in the SuHx model of PAH, with significant downregulation of metabolic enzymes involved in fatty acid transport, beta oxidation, and glucose oxidation compared to controls. Treatment with ACTZ led to a pattern of gene expression suggestive of restored metabolic balance in the RV with significantly increased beta oxidation transcripts. In addition, the FAO transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) was significantly downregulated in untreated SuHx rats compared to controls, and ACTZ treatment restored its expression levels. These metabolic changes were associated with amelioration of the hemodynamic and echocardiographic markers of RVH in the ACTZ-treated SuHx animals and attenuation of cardiomyocyte hypertrophy and RV fibrosis.Conclusion: Acetazolamide treatment prevents the development of PAH, RVH, and fibrosis in the SuHx rat model of severe PAH, improves RV function, and restores the RV metabolic profile.
Hypofunction of Circulating Endothelial Progenitor Cells and Aggravated Severity in Elderly Male Patients With Non-ST Segment Elevation Myocardial Infarction: Its Association With Systemic Inflammation
Authors: Zeng Lijin , Zhang Cong , Zhu Yuanting , Liu Zhihao , Liu Gexiu , Zhang Bin , Tu Chang , Yang Zhen 
Published: June 2021

Background: Aging patients easily suffer from non-ST segment elevation myocardial infarction (NSTEMI). Our previous studies revealed declined function of endothelial progenitor cells (EPCs) in the elderly. However, the impact of aging on EPC function and severity in male NSTEMI patients and its possible mechanism is unclear until now.Methods: We measured the circulating EPC function including migration, proliferation, and adhesion in aging or young male patients with NSTEMI. The GRACE and TIMI risk score were evaluated. Plasma levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) were also detected in all patients.Results: Compared with the young group, the old male patients with NSTEMI had higher GRACE score and TIMI score and decreased function of circulating EPCs. EPC function was negatively correlated with GRACE score and TIMI score. IL-6 and IL-17 level were higher in the old group than those in the young group. There was a significant negative correlation between EPC function and IL-6 or IL-17. Moreover, IL-6 and IL-17 positively correlated with GRACE and TIMI score. Age was positively related with GRACE or TIMI score and plasma level of IL-6 or IL-17, but inversely correlated with EPC function.Conclusions: The current study firstly illustrates that the age-related decrement in EPC function is related to the severity of NSTEMI in male patients, which may be connected with systemic inflammation. These findings provide novel insights into the pathogenetic mechanism and intervention target of aging NSTEMI.
Acetate Does Not Affect Palmitate Oxidation and AMPK Phosphorylation in Human Primary Skeletal Muscle Cells
Authors: González Hernández Manuel A. , Blaak Ellen E. , Hoebers Nicole T. H. , Essers Yvonne P. G. , Canfora Emanuel E. , Jocken Johan W. E. 
Published: June 2021

Our recent in vivo human studies showed that colonic administration of sodium acetate (SA) resulted in increased circulating acetate levels, which was accompanied by increments in whole-body fat oxidation in overweight-obese men. Since skeletal muscle has a major role in whole-body fat oxidation, we aimed to investigate effects of SA on fat oxidation and underlying mechanisms in human primary skeletal muscle cells (HSkMC). We investigated the dose (0–5 mmol/L) and time (1, 4, 20, and 24 h) effect of SA on complete and incomplete endogenous and exogenous oxidation of 14C-labeled palmitate in HSkMC derived from a lean insulin sensitive male donor. Both physiological (0.1 and 0.25 mmol/L) and supraphysiological (0.5, 1 and 5 mmol/L) concentrations of SA neither increased endogenous nor exogenous fat oxidation over time in HSkMC. In addition, no effect of SA was observed on Thr172-AMPKα phosphorylation. In conclusion, our previously observed in vivo effects of SA on whole-body fat oxidation in men may not be explained via direct effects on HSkMC fat oxidation. Nevertheless, SA-mediated effects on whole-body fat oxidation may be triggered by other mechanisms including gut-derived hormones or may occur in other metabolically active tissues.
Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction
Authors: Han Falan , Pang Shuchao , Sun Zhaoqing , Cui Yinghua , Yan Bo 
Published: June 2021

BackgroundAcute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 (ATG16L1) is a key regulatory factor of autophagy and plays an important role in induced autophagy. In the cardiovascular system, autophagy is essential to preserve the homeostasis and function of the heart and blood vessels. No studies have hitherto examined the association between AMI and ATG16L1 gene promoter.MethodsWe conducted a case-control study, using polymerase chain reaction and sequencing techniques, dual luciferase reporter assay, and electrophoretic mobility shift assay, to analyze genetic and functional variation in the ATG16L1 gene promoter between AMI and controls. A variety of statistical analyses were used to analyze the allele and genotype frequencies and the relationship between single-nucleotide polymorphisms (SNPs) and AMI.ResultsIn all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three ATG16L1 gene promoter mutations [g.233250693 T &gt; C (rs185213911), g.233250946 G &gt; A (rs568956599), g.233251133 C &gt; G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of ATG16L1 gene promoter in HEH2, HEK-293, and H9c2 cells (P &lt; 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors (P &lt; 0.01).ConclusionATG16L1 gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the ATG16L1 gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors.
Comparison of the Clinical Value of miRNAs and Conventional Biomarkers in AMI: A Systematic Review
Authors: Wang Baofu , Li Yang , Hao Xuezeng , Yang Jingjing , Han Xiaowan , Li Haiyan , Li Tong , Wang Dayang , Teng Yu , Ma Liang , Li Yao , Zhao Mingjing , Wang Xian 
Published: June 2021

Background/Aims:This study aimed to compare the clinical value of the peak time point and area under the curve (AUC) of miRNAs and conventional biomarkers in acute myocardial infarction (AMI).Methods:A literature search was carried out in PubMed, Web of Science, Embase, and Cochrane systematically. Screening studies, extracting data, and assessing article quality were performed independently by two researchers. Also, the names of miRNAs in the included studies were standardized by the miRBase database.Results:A total of 40 studies, encompassing 6,960 participants, were included in this systematic review. The samples of circulating miRNAs were mainly from the plasma. The results of this systematic review displayed that miR-1-3p, miR-19b-3p, miR-22-5p, miR-122-5p, miR-124-3p, miR-133a/b, miR-134-5p, miR-150-5p, miR-186-5p, miR-208a, miR-223-3p, miR-483-5p, and miR-499a-5p reached peak time earlier and showed a shorter time window than the conventional biomarkers despite the different collection times of initial blood samples. miR-1-3p, miR-19b-3p, miR-133a/b, miR-208a/b, miR-223-3p, miR-483-5p, and miR-499a-5p were shown to be more valuable than classical biomarkers for the early diagnosis of AMI, and these miRNAs appeared to have the most potential biomarkers within 4 h of the onset of symptoms except miR-133a/b and miR-208b. Moreover, combined miRNAs or miRNAs combined with classical biomarkers could compensate for the deficiency of single miRNA and conventional biomarker in sensitivity or specificity for an optimal clinical value.Conclusions:miR-1-3p, miR-19b-3p, miR-208a, miR-223-3p, miR-483-5p, and miR-499a-5p are promising biomarkers for AMI due to their satisfactory diagnostic accuracy and short time window (within 4 h of the onset of symptoms).
Driving β2- While Suppressing α-Adrenergic Receptor Activity Suppresses Joint Pathology in Inflammatory Arthritis
Authors: Bellinger Denise L. , Wood Carlo , Wergedal Jon E. , Lorton Dianne 
Published: June 2021

ObjectiveHypersympathetic activity is prominent in rheumatoid arthritis, and major life stressors precede onset in ~80% of patients. These findings and others support a link between stress, the sympathetic nervous system and disease onset and progression. Here, we extend previous research by evaluating how selective peripherally acting α/β2-adrenergic drugs affect joint destruction in adjuvant-induced arthritis.MethodsComplete Freund’s adjuvant induced inflammatory arthritis in male Lewis rats. Controls received no treatment. Arthritic rats then received vehicle or twice-daily treatment with the α-adrenergic antagonist, phentolamine (0.5 mg/day) and the β2-adrenergic agonist, terbutaline (1200 µg/day, collectively named SH1293) from day (D) of disease onset (D12) through acute (D21) and severe disease (D28). Disease progression was assessed in the hind limbs using dorsoplantar widths, X-ray analysis, micro-computed tomography, and routine histology on D14, D21, and D28 post-immunization.ResultsOn D21, SH1293 significantly attenuated arthritis in the hind limbs, based on reduced lymphocytic infiltration, preservation of cartilage, and bone volume. Pannus formation and sympathetic nerve loss were not affected by SH1293. Bone area and osteoclast number revealed high- and low-treatment-responding groups. In high-responding rats, treatment with SH1293 significantly preserved bone area and decreased osteoclast number, data that correlated with drug-mediated joint preservation. SH1293 suppressed abnormal bone formation based on reduced production of osteophytes. On D28, the arthritic sparing effects of SH1293 on lymphocytic infiltration, cartilage and bone sparing were maintained at the expense of bone marrow adipocity. However, sympathetic nerves were retracted from the talocrural joint.Conclusion and SignificanceOur findings support a significant delay in early arthritis progression by treatment with SH1293. Targeting sympathetic neurotransmission may provide a strategy to slow disease progression.
Microstructure Evolution and Shear Property of Cu-In Transient Liquid Phase Sintering Joints
Authors: Jiang Bang , Zhang Qiaoxin , Shi Lin , Zhu Chundong , Chen Zhiwen , Liu Li , Shi Yan 
Published: June 2021

Transient liquid phase sintering (TLPS) is a promising joining technology that can achieve high temperature resistant solder joints at low temperature, showing excellent potential in power electronics. In this work, Cu/Cu-In/Cu solder joints were successfully prepared by TLPS process. The effects of bonding pressure and holding time on the microstructure and shear strength of Cu-In TLPS joints at 260 and 320°C were studied. The results showed that as bonding pressure increased from 0.1–0.6 MPa, the porosity decreased and shear strength increased significantly. No obvious change was found as bonding pressure continued to increase to 1 MPa. As holding time increased at 260°C, Cu11In9 was formed and gradually transformed to Cu2In that can withstand elevated temperature. Meanwhile, the porosity decreased while shear strength increased. It was calculated that volume expansion (12.74%) occurred during the phase transition from Cu11In9 to Cu2In. When bonding temperature increased to 320°C, only Cu2In was detected and then gradually transformed to Cu7In3 with the growing holding time. As holding time reached 120 min, their porosity increased and lead to weak shear strength due to volume shrinkage (15.43%) during the phase transition from Cu2In to Cu7In3.
Long Circulation of PEG-TRAIL Improves Anti-Hepatic Fibrosis Effect of TRAIL Via Targeting Activated Hepatic Stellate Cells
Authors: Lu Bingyun , Peng Lijun , Luo Shenggen , Zhou Jing’e , Xu Nan , Dong Chunxiu , Yan Zhiqiang , Li Huiyi , Li Qinghua 
Published: June 2021

Background: The short half-life of TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) greatly limits its clinical application. This study was aimed to improve its potency on liver fibrosis through PEG (polyethylene glycol) modification prolonging the half-life of TRAIL.Methods: PEG, TRAIL, and the chemically synthesized complex PEG-TRAIL were used to treat 3T3 and LX-2 cells and liver fibrotic mice. In vitro, cell viability, apoptosis, and fibrosis were investigated using CCK-8 (cell counting kit-8) assay, flow cytometry, and Western blotting, respectively. In vivo, Sirius red staining, immunohistochemistry, and α-SMA (α-smooth muscle actin)/TUNEL (terminal deoxynucleotidyl transferase dUTP [2'-deoxyuridine 5'-triphosphate] nick end labeling) double-labeling immunofluorescence (IF) were performed after various treatments for liver fibrotic mice. The fibrotic liver was subjected to DR4 (death receptor 4)/TRAIL double-labeling IF to assess the retention of TRAIL enhanced by PEGylation.Results: The cells treated with PEG-TRAIL showed lower cell viability, higher apoptosis level, and stronger anti-fibrotic effect compared with PEG or TRAIL treatment. In vivo, PEGylated TRAIL exhibited a longer circulation than TRAIL did. Compared with TRAIL treatment, PEG-TRAIL caused a significant reduction of α-SMA and a markedly increase of apoptotic aHSCs. PEGylation is more likely to prolong the retention of TRAIL in circulation and enhance the possibility to target aHSCs and DR4-positive (DR4+) cells in the liver.Conclusion: PEG-TRAIL presents better anti-fibrotic and proapoptotic effects, for which, the prolonged circulation half-life in vivo may account. The PEG-TRAIL may serve as a new clinical therapeutic for liver fibrosis in the future.
Regional Spontaneous Neural Activity Alterations in Type 2 Diabetes Mellitus: A Meta-Analysis of Resting-State Functional MRI Studies
Authors: Liu Jieke , Li Yong , Yang Xi , Xu Hao , Ren Jing , Zhou Peng 
Published: June 2021

Objective: Resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed inconsistent regional spontaneous neural activity alterations in patients with type 2 diabetes mellitus (T2DM). The aim of our meta-analysis was to identify concordant regional spontaneous neural activity abnormalities in patients with T2DM.Methods: A systematic search was conducted to identify voxel-based rs-fMRI studies comparing T2DM patients with healthy controls. The permutation of subject images seed-based d mapping (SDM) was used to quantitatively estimate the regional spontaneous neural activity abnormalities in patients with T2DM. Metaregression was conducted to examine the associations between clinical characteristics and functional alterations.Results: A total of 16 studies with 19 datasets including 434 patients with T2DM and 391 healthy controls were included. Patients with T2DM showed hypoactivity in the right medial superior frontal gyrus, right superior temporal gyrus, and left lingual gyrus, whereas hyperactivity in the right cerebellum. Metaregression analysis identified negative correlation between regional activity in the medial superior frontal and anterior cingulate gyri and illness duration of patients with T2DM.Conclusion: The patterns of regional spontaneous neural activity alterations, characterized by hypoactivity in the medial pre-frontal cortex, visual cortex, and superior temporal gyrus, whereas hyperactivity in the cerebellum, might represent the underlying neuropathological mechanisms of T2DM.
Lipid Levels and 3-Month Prognosis After Spontaneous Intracerebral Hemorrhage in Women
Authors: Feng Hao , Wang Xin , Wang Wenjuan , Zhao Xingquan 
Published: June 2021

Background: The relationship between serum lipids levels and prognosis after spontaneous intracerebral hemorrhage (ICH) is still unclear. We aim to examine the association between lipid levels and 3-month ICH prognosis in women.Method: We went through a registry of spontaneous ICH cases and selected female patients to study according to our criteria. We collected demographic, clinical, and laboratory information and evaluated serum triglyceride (TG) levels, total cholesterol (TC) levels, low-density cholesterol (LDLC) levels, high-density cholesterol (HDLC) levels, non-high-density cholesterol (non-HDLC) levels, and 3-month modified Rankin Scale (mRS). Multivariate logistic regression was performed, and receiver operating characteristic (ROC) curves were plotted to explore the relationship between serum lipid levels and 3-month ICH clinical outcomes.Results: Two hundred six female patients were included in this study, and 96 (46.6%) of them had poor functional outcomes. In the univariate analysis, low TG (p = 0.006), TC (p = 0.025), LDLC (p = 0.001), non-HDLC (p &lt; 0.001) levels, and high HDL (p = 0.036) levels were associated with poor 3-month clinical outcomes in women. In the multivariate logistic regression, low levels of TG (OR = 0.711, 95% CI = 0.542–0.933, p = 0.014), TC (OR = 0.523, 95% CI = 0.304–0.903, p = 0.020), LDLC (OR = 0.538, 95% CI = 0.307–0.942, p = 0.030), non-HDLC (OR = 0.327, 95% CI = 0.177–0.603, p &lt; 0.001), and a high level of HDLC (OR = 2.075, 95% CI = 1.064–4.047, p = 0.032) with area under the curve (AUC) of 0.610, 0.590, 0.630, 0.645, and 0.415, respectively, remained as independent indicators of poor prognosis at 3 months after adjusting for confounding factors.Conclusion: Low levels of TG, TC, LDLC, non-HDLC, and high levels of HDLC were independently associated with poor prognosis of spontaneous ICH in women.
Dual Task Effects on Speed and Accuracy During Cognitive and Upper Limb Motor Tasks in Adults With Stroke Hemiparesis
Authors: Kim Hogene , Kim Hyun-Ki , Kim Nayoung , Nam Chang S. 
Published: June 2021

BackgroundAdults with stroke need to perform cognitive–motor dual tasks during their day-to-day activities. However, they face several challenges owing to their impaired motor and cognitive functions.ObjectiveThis case-controlled pilot study investigates the speed and accuracy tradeoffs in adults with stroke while performing cognitive–upper limb motor dual tasks.MethodsTen adults with stroke and seven similar-aged controls participated in this study. The participants used a robotic arm for the single motor task and participated in either the serial sevens (S7) or the controlled oral word association test (COWAT) for single-cognitive task. For the dual task, the participants performed the motor and cognitive components simultaneously. Their speed and accuracy were measured for the motor and cognitive tasks, respectively.ResultsTwo-sample t-statistics indicated that the participants with stroke exhibited a lower motor accuracy in the cross task than in the circle task. The cognitive speed and motor accuracy registered by the subjects with stroke in the dual task significantly decreased. There was a negative linear correlation between motor speed and accuracy in the subjects with stroke when the COWAT task was performed in conjunction with the cross task (ρ = −0.6922, p = 0.0388).ConclusionsThis study proves the existence of cognitive–upper limb motor interference in adults with stroke while performing dual tasks, based on the observation that their performance during one or both dual tasks deteriorated compared to that during the single task. Both speed and accuracy were complementary parameters that may indicate clinical effectiveness in motor and cognitive outcomes in individuals with stroke.