bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of 3D Hepatic Plate-Like Liver Model for Statin-Induced Hepatotoxicity Evaluation
Authors: Xu Jiecheng , Pan Daogang , Liao Wei , Jia Zhidong , Pan Mingxin , Weng Jun , Han Xu , Li Shao , Li Yang , Liang Kangyan , Zhou Shuqin , Peng Qing , Gao Yi 
Published: March 2022

Background: Drug-induced liver injury is one of the main reasons of withdrawals of drugs in postmarketing stages. However, an experimental model(s) which can accurately recapitulates liver functions and reflects the level of drug hepatotoxicity is lack. In this study, we assessed drug hepatotoxicity using a novel three-dimensional hepatic plate-like hydrogel fiber (3D-P) co-culture system.Methods: During the 28-days culture period, the liver-specific functions, hepatocyte polarity, sensitivity of drug-induced toxicity of 3D-P co-culture system were evaluated with 2D co-culture, collagen sandwich co-culture, 3D hybrid hydrogel fiber co-culture and human primary hepatocytes as controls. High-content imaging and analysis (HCA) methods were used to explore the hepatotoxicity mechanism of five statins.Results: The 3D-P co-culture system showed enhancing liver-specific functions, cytochrome P450 enzymes (CYPs) metabolic activity and bile excretion, which were considered to result from improved hepatocyte polarity. Three of the statins may cause acute or chronic hepatotoxicity by via different mechanisms, such as cholestatic liver injury.Conclusion: Our 3D-P co-culture system is characterized by its biomimetic hepatic plate-like structure, long-term stable liver specificity, and prominent bile secretion function, making it applicable for acute/chronic drug hepatotoxicity assessments.
Knee Joint Menisci Are Shock Absorbers: A Biomechanical In-Vitro Study on Porcine Stifle Joints
Authors: Seitz Andreas M. , Schwer Jonas , de Roy Luisa , Warnecke Daniela , Ignatius Anita , Dürselen Lutz 
Published: March 2022

The aim of this biomechanical in vitro study was to answer the question whether the meniscus acts as a shock absorber in the knee joint or not. The soft tissue of fourteen porcine knee joints was removed, leaving the capsuloligamentous structures intact. The joints were mounted in 45° neutral knee flexion in a previously validated droptower setup. Six joints were exposed to an impact load of 3.54 J, and the resultant loss factor (η) was calculated. Then, the setup was modified to allow sinusoidal loading under dynamic mechanical analysis (DMA) conditions. The remaining eight knee joints were exposed to 10 frequencies ranging from 0.1 to 5 Hz at a static load of 1210 N and a superimposed sinusoidal load of 910 N (2.12 times body weight). Forces (F) and deformation (l) were continuously recorded, and the loss factor (tan δ) was calculated. For both experiments, four meniscus states (intact, medial posterior root avulsion, medial meniscectomy, and total lateral and medial meniscectomy) were investigated. During the droptower experiments, the intact state indicated a loss factor of η = 0.1. Except for the root avulsion state (−15%, p = 0.12), the loss factor decreased (p &lt; 0.046) up to 68% for the total meniscectomy state (p = 0.028) when compared to the intact state. Sinusoidal DMA testing revealed that knees with an intact meniscus had the highest loss factors, ranging from 0.10 to 0.15. Any surgical manipulation lowered the damping ability: Medial meniscectomy resulted in a reduction of 24%, while the resection of both menisci lowered tan δ by 18% compared to the intact state. This biomechanical in vitro study indicates that the shock-absorbing ability of a knee joint is lower when meniscal tissue is resected. In other words, the meniscus contributes to the shock absorption of the knee joint not only during impact loads, but also during sinusoidal loads. The findings may have an impact on the rehabilitation of young, meniscectomized patients who want to return to sports. Consequently, such patients are exposed to critical loads on the articular cartilage, especially when performing sports with recurring impact loads transmitted through the knee joint surfaces.
Myocardial Extracellular Volume Fraction Measured by Cardiac Magnetic Resonance Imaging Negatively Correlates With Cardiomyocyte Breadth in a Healthy Porcine Model
Authors: Zhang Shi-Jun , Chang Di , Jin Ji-Yang , Wang Ya-Ling , Wang Lin , Wang Yuan-Cheng , Wang Zhen , Ju Shenghong 
Published: March 2022

BackgroundThe extracellular volume fraction (ECV) derived from cardiac magnetic resonance imaging (MRI) is extensively used to evaluate myocardial fibrosis. However, due to the limited histological verification in healthy individuals, it remains unclear whether the size of cardiomyocytes may play a potential role in the physiological changes of ECV. The aim of this study was to examine the association between cardiomyocyte size and myocardial ECV by using a healthy porcine model.MethodsSixteen domestic healthy pigs were anesthetized and underwent cardiac MRI with mechanical controlled breathing. Intravenous contrast medium was introduced at a dose of 0.2–0.25 mmol/kg. The interventricular septum ECV was calculated using an established MRI procedure, which was based on the pre- and post-contrast T1 values of the heart and individual blood hematocrit. The cardiomyocyte breadth (CmyB) in cross section was measured by hematoxylin and eosin staining to reflect the cardiomyocyte size.ResultsData were successfully acquired from 14 pigs. The CmyB was obtained from the myocardial tissues corresponding to the region of interest on cardiac MRI. The mean ± SD of the ECV was 0.253 ± 0.043, and the mean ± SD of the CmyB was 10.02 ± 0.84 μm. The ECV exhibited a negative correlation with the CmyB (r = −0.729, p = 0.003).ConclusionThe myocardial ECV detected by cardiac MRI is negatively correlated with the CmyB in healthy pigs, demonstrating that the size of cardiomyocytes is potentially associated with the ECV under physiological conditions.
Association Between Circulating Retinol-Binding Protein 4 and Adverse Cardiovascular Events in Stable Coronary Artery Disease
Authors: Qian Ke , Yan Xin , Xu Cheng , Fang Yijia , Ma Moshuang 
Published: March 2022

BackgroundThe predictive role of retinol-binding protein 4 (RBP4) in the adverse prognosis of patients with stable coronary artery disease (CAD) has not been well-defined. We thus conducted this cohort study to investigate the association between circulating RBP4 level and major adverse cardiovascular events (MACEs) in Chinese patients with stable CAD.MethodsPatients with stable CAD and serum RBP4 concentration measurement at admission between July 2012 and January 2015 were included. The primary outcome in this study was incident MACEs, which included acute coronary syndrome, heart failure, stroke, peripheral vascular disease, and cardiovascular death. Cox proportional hazards regression was adopted to investigate the association between RBP4 and the incidence of MACEs.ResultsA total of 840 patients with stable CAD were analyzed. The mean age of patients was 61.2 ± 15.9 years, and 56.1% of them were men. After a median follow-up of 2.3 years, 129 MACEs were observed. Compared to participants exposed to the first quartile of serum RBP4 level, those in the second, the third, and the fourth quartiles had associated hazard ratios (HRs) of 2.38 [95% confidence interval (CI): 1.33–4.26], 2.35 (95% CI: 1.31–4.21), and 2.27 (95% CI: 1.28–4.04) after adjusted for confounders, respectively. Every 5 μg/ml increment in serum RBP4 concentration was associated with an adjusted HR of 1.13 (95% CI: 1.05–1.22) for the occurrence of MACEs. Subgroup analyses suggested no significant modifying effects of baseline characteristics for the association between RBP4 and MACEs in patients with stable CAD.ConclusionOur finding suggested that the higher circulating RBP4 level was significantly associated with an increased risk of MACEs in patients with stable CAD.
Methodological Quality and Risk of Bias Assessment of Cardiovascular Disease Research: Analysis of Randomized Controlled Trials Published in 2017
Authors: Baasan Odgerel , Freihat Omar , Nagy David U. , Lohner Szimonetta 
Published: March 2022

BackgroundAll randomized-controlled trials (RCTs) are required to follow high methodological standards. In this study, we aimed to assess the methodological quality of published cardiovascular clinical research trials in a representative sample of RCTs published in 2017.MethodsCochrane Central Register of Controlled Trials was used to identify cardiovascular clinical research trials with adult participants published in 2017. Overall, 250 (10%) RCTs were randomly selected from a total of 2,419 studies. Data on general trial characteristics were extracted and the risk of bias (RoB) was determined.ResultsOverall, 86% of RCTs have reported at least one statistically significant result, with the primary outcome significant in 69%, treatment favored in 55%, and adverse events reported in 68%. Less than one-third (29%) of trials were overall low RoB, while the other two-thirds were rated unclear (40%) or with high RoB (31%). Sequence generation, allocation concealment, and selective reporting were the domains most often rated with high RoB. Drug trials were more likely to have low RoB than non-drug trials. Significant differences were found in RoB for the allocation concealment and blinding of participants and personnel between industry-funded and non-industry-funded trials, with industry-funded trials more often rated at low RoB.ConclusionAlmost two-thirds of RCTs in the field of cardiovascular disease (CVD) research, were at high or unclear RoB, indicating a need for more rigorous trial planning and conduct. Prospective trial registration is a factor predicting a lower risk of bias.
Clinical Outcomes of Permanent Left Bundle Branch Area Pacing in Patients With Left Bundle Branch Block and Left Ventricular Ejection Fraction >35 vs. ≤35%
Authors: Jiang Zhixin , Wu Tian , Wu Yixian , Chen Zenghong , Yang Wen , Chen Chongchong , Zhou Xiujuan , Shan Qijun 
Published: March 2022

AimsThe present study aimed to compare the effects of left bundle branch area pacing (LBBAP) on cardiac function and clinical outcomes in patients with left bundle branch block (LBBB) and left ventricular ejection fraction (LVEF) &gt;35 vs. ≤35%.Methods and ResultsThirty-six consecutive patients with LBBB and LVEF &lt;50% were enrolled. All patients were followed up for a mean of 6 months. The successful LBBAP was defined as a paced QRS complex presented as right bundle branch block (RBBB) morphology and QRSd &lt; 130 ms. Echocardiography parameters, pacing parameters and clinical outcomes were collected. The successful LBBAP was achieved in 77.8% of all cases (28/36). In LVEF &gt; 35% group (70 ± 8 years, 9 male), the success rate was 81.0% (17/21). QRSd significantly decreased from 174 ± 23 ms to 108 ± 13 ms (P &lt; 0.001). The pacing threshold and R-wave amplitude were 0.6 ± 0.2 V @ 0.5 ms and 12 ± 7 mV, respectively. In LVEF ≤ 35% group (69 ± 5 years, 9 male), the success rate was 73.3% (11/15) with QRSd decreasing from 188 ± 25 ms to 107 ± 11 ms (P &lt; 0.001). The hyperresponders to LBBAP (functional recovery and LVEF ≥ 50%) in LVEF &gt; 35% group was 52.9%, which were almost twice of that in LVEF ≤ 35% group (33.3%). Whether patients had LBBAP or left ventricular septal pacing (LVSP), patients in the LVEF &gt; 35% group showed significantly lower incidence of heart failure hospitalizations or death from any cause (hazard ratio in LVEF &gt; 35% group, 0.22; 95%CI, 0.06 to 0.75, P = 0.011).ConclusionsLBBAP can significantly shorten the QRSd and improve cardiac function in LBBB patients with either LVEF &gt; 35 or ≤ 35%. LBBAP should be considered as an effective therapy for preventing the deterioration of cardiac function in early-stage heart failure patients with LBBB and LVEF &gt; 35%.
Effects of Antidiabetic Drugs on Endothelial Function in Patients With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis
Authors: Wang Yuhan , Yao Mingyan , Wang Jincheng , Liu Hongzhou , Zhang Xuelian , Zhao Ling , Hu Xiaodong , Guan Haixia , Lyu Zhaohui 
Published: March 2022

BackgroundThe changes of endothelial function in type 2 diabetes mellitus (T2DM) patients are closely associated with the development of cardiovascular disease (CVD). However, it is still unclear whether commonly used antidiabetic drugs can improve endothelial function. Flow-mediated dilation (FMD) is a noninvasive tool for evaluating endothelial function, which typically examines changes in the brachial artery diameter in response to ischemia using ultrasound. We performed a network meta-analysis (NMA) to explore the associations between changes in endothelial function and antidiabetic drugs by evaluating FMD in T2DM patients.MethodsWe systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until January 25, 2022 with no language restriction. The primary outcome was FMD change in all studies, and we performed subgroup analysis in T2DM patients without CVD. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs).ResultsFrom the 1,987 candidate articles identified in the initial search, 30 RCTs were eventually included in the analysis. In all studies, glucagon-like peptide-1 receptor (GLP-1R) agonists [MD = 3.70 (1.39–5.97)], TZD [MD = 1.96 (0.006–3.89)] produced improvement of FMD change compared to lifestyle intervention. GLP-1R agonists [MD = 3.33 (1.36–5.34) and MD = 3.30 (1.21–5.43)] showed significantly greater improvements in FMD change in pairwise comparisons with sulfonylureas and placebo. SGLT-2i also showed efficacy compared to sulfonylureas (MD = 1.89, 95% CI, 0.10, 3.75). In studies of T2DM patients without CVD, GLP-1R agonists [MD = 3.53 (1.24–5.76)], and TZD [MD = 2.30 (0.27–3.24)] produced improvements in FMD change compared to lifestyle treatment. GLP-1R agonists [MD = 3.25 (1.13–5.40), and MD = 3.85 (1.68–6.13)] showed significantly greater improvements in pairwise comparisons with sulfonylureas, and placebo.ConclusionIn T2DM patients, both GLP-1R agonists, SGLT-2i and TZD have favorable effects to improve endothelial function in T2DM patients. In T2DM patients without CVD, GLP-1R agonists had a greater effect to improve endothelial function than sulfonylureas. These suggested that GLP-1R agonists are associated with significantly improved endothelial function in T2DM patients.
First Assessment of Mercury (Hg) Concentrations in Skin and Carapace of Flatback Turtles (Natator depressus) (Garman) From Western Australia
Authors: Schneider Larissa , Tucker Anton D. , Vincent Kathryn , Fossette Sabrina , Young Erina J. , Whiting Scott D. 
Published: March 2022

Mercury pollution in the surface ocean has more than doubled over the past century. Within oceanic food webs, sea turtles have life history characteristics that make them especially vulnerable to mercury (Hg) accumulation. In this study we investigated Hg concentrations in the skin and carapace of nesting flatback turtles (Natator depressus) from two rookeries in Western Australia. A total of 50 skin samples and 52 carapace samples were collected from nesting turtles at Thevenard Island, and 23 skin and 28 carapace samples from nesting turtles at Eighty Mile Beach. We tested the influence of turtle size on Hg concentrations, hypothesising that larger and likely older adult turtles would exhibit higher concentrations due to more prolonged exposure to Hg. We compared the rookeries, hypothesising that the turtles from the southern rookery (Thevenard Island) were more likely to forage and reside in the Pilbara region closer to industrial mining activity and loading ports (potential exposure to higher environmental Hg concentrations) with turtles from the northern rookery (Eighty Mile Beach) more likely to reside and feed in the remote Kimberley. Turtles from the Eighty Mile Beach rookery had significantly higher skin Hg concentrations (x̄ = 19.4 ± 4.8 ng/g) than turtles from Thevenard Island (x̄ = 15.2 ± 5.8 ng/g). There was no significant difference in carapace Hg concentrations in turtles between Eighty Mile Beach (x̄ = 48.4 ± 21.8 ng/g) and Thevenard Island (x̄ = 41.3 ± 16.5 ng/g). Turtle size did not explain Hg concentrations in skin samples from Eighty Mile Beach and Thevenard Island, but turtle size explained 43.1% of Hg concentrations in the carapace of turtles from Eighty Mile Beach and 44.2% from Thevenard Island. Mercury concentrations in the flatback turtles sampled in this study are relatively low compared to other sea turtles worldwide, likely a result of the generally low concentrations of Hg in the Australian environment. Although we predicted that mining activities would influence flatback turtle Hg bioaccumulations, our data did not support this effect. This may be a result of foraging ground overlap between the two rookeries, or the predominant wind direction carrying atmospheric Hg inland rather than seaward. This is the first Hg study in skin and carapace of flatback turtles and represents a baseline to compare Hg contamination in Australia’s surrounding oceans.
Case Report: Novel Mutations in the PCCB Gene Causing Late-Onset Propionic Acidemia
Authors: Ji Guang , Liu Yaling , Song Xueqin , Li Zhenfei 
Published: March 2022

Introduction: Propionic acidemia is an autosomal recessive metabolic disorder and the patients with adult onset are very rare.Methods: Two PCCB mutations were identified. Clinical data were collected from a patient, and metabolic screening and clinical exome sequencing analysis were performed.Results: Two novel mutations were identified in the PCCB gene: M1:c.404_406del:p.G135del and M2:c.632C&gt;T:p.T211I.Conclusion: Late-onset propionic acidemia should be taken into account, and metabolic screening as well as gene analysis should be performed to make a definite diagnosis timely.
Long Non-coding RNA HOXA11-AS Facilitates Proliferation of Lung Adenocarcinoma Cells via Targeting the Let-7c-5p/IGF2BP1 Axis
Authors: Lv Xiaodong , Fang Zhixian , Qi Weibo , Xu Yufen , Chen Wenyu 
Published: March 2022

Objective: This study investigates the relationship between the HOXA11-AS/let-7c-5p/IGF2BP1 regulatory axis and lung adenocarcinoma.Methods: The expression levels of HOXA11-AS, let-7c-5p, and IGF2BP1 were evaluated in LUAD tissue and cell lines. Subcellular fractionation detection assay was adopted to verify the HOXA11-AS distribution in LUAD cells. The interaction relationship between let-7c-5p and HOXA11-AS or IGF2BP1 was validated by dual-luciferase reporter detection. In RNA binding protein immunoprecipitation assay, the binding relationship between HOXA11-AS and let-7c-5p was identified. The cell viability of transfected cells was tested by the Cell Counting Kit-8 assay. The mouse xenograft model was used to identify the effect of HOXA11-AS on tumor growth in vivo.Results: Upregulation of lncRNA HOXA11-AS was found in LUAD, and suppression of HOXA11-AS could suppress the proliferative ability of LUAD cells. The let-7c-5p was expressed to be downregulated, which played an inhibitory role in LUAD cell proliferation. Let-7c-5p was negatively regulated by HOXA11-AS. HOXA11-AS promoted LUAD cell proliferation, while let-7c-5p had an inverse effect. Besides, IGF2BP1, regulated by let-7c-5p, had a positive relation with HOXA11-AS, while overexpression of IGF2BP1 could suppress the inhibition of silencing HOXA11-AS on LUAD cell proliferation. Experiments on mice confirmed that HOXA11-AS facilitated LUAD cell growth in vivo through regulating the let-7c-5p/IGF2BP1 axis.Conclusion: HOXA11-AS promoted LUAD cell proliferation by targeting let-7c-5p/IGF2BP1, which could be potential molecular targets for LUAD.
Case Report: Severe Rhabdomyolysis and Multiorgan Failure After ChAdOx1 nCoV-19 Vaccination
Authors: Cirillo Emilia , Esposito Ciro , Giardino Giuliana , Azan Gaetano , Fecarotta Simona , Pittaluga Stefania , Ruggiero Lucia , Barretta Ferdinando , Frisso Giulia , Notarangelo Luigi Daniele , Pignata Claudio 
Published: March 2022

BackgroundSevere skeletal muscle damage has been recently reported in patients with SARS-CoV-2 infection and as a rare vaccination complication.Case summaryOn Apr 28, 2021 a 68-year-old man who was previously healthy presented with an extremely severe rhabdomyolysis that occurred nine days following the first dose of SARS-CoV-2 ChAdOx1 nCov-19 vaccination. He had no risk factors, and denied any further assumption of drugs except for fermented red rice, and berberine supplement. The clinical scenario was complicated by a multi organ failure involving bone marrow, liver, lung, and kidney. For the rapid increase of the inflammatory markers, a cytokine storm was suspected and multi-target biologic immunosuppressive therapy was started, consisting of steroids, anakinra, and eculizumab, which was initially successful resulting in close to normal values of creatine phosphokinase after 17 days of treatment. Unfortunately, 48 days after the vaccination an accelerated phase of deterioration, characterized by severe multi-lineage cytopenia, untreatable hypotensive shock, hypoglycemia, and dramatic increase of procalcitonin (PCT), led to patient death.ConclusionPhysicians should be aware that severe and fatal rhabdomyolysis may occur after SARS-CoV2 vaccine administration.
Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases
Authors: Feng Yi , Chen Zheng , Tu Shao-Qin , Wei Jia-Ming , Hou Yu-Luan , Kuang Zhi-Li , Kang Xiao-Ning , Ai Hong 
Published: March 2022

Periodontitis is a chronic inflammatory and destructive disease caused by periodontal microbial infection and mediated by host immune response. As the main cause of loosening and loss of teeth in adults, it is considered to be one of the most common and serious oral diseases in the world. The co-existence of periodontitis and systemic chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, diabetes and so on is very common. It has been found that interleukin-17A (IL-17A) secreted by various innate and adaptive immune cells can activate a series of inflammatory cascade reactions, which mediates the occurrence and development of periodontitis and related systemic chronic inflammatory diseases. In this work, we review the role of IL-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases, and briefly discuss the therapeutic potential of cytokine targeted agents that modulate the IL-17A signaling. A deep understanding of the possible molecular mechanisms in the relationship between periodontitis and systemic diseases will help dentists and physicians update their clinical diagnosis and treatment ideas.