bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between 2D- and 3D-Speckle-Tracking Longitudinal Strain and Cardiovascular Magnetic Resonance Evidence of Diffuse Myocardial Fibrosis in Heart Transplant Recipients
Authors: Sun Wei , Shen Xuehua , Wang Jing , Zhu Shuangshuang , Zhang Yanting , Wu Chun , Xie Yuji , Yang Yun , Dong Nianguo , Wang Guohua , Li Yuman , Lv Qing , Liang Bo , Zhang Li , Xie Mingxing 
Published: December 2021

Objective: This study aimed to: (1) evaluate the association between myocardial fibrosis (MF) quantified by extracellular volume fraction (ECV) and myocardial strain measured by two-dimensional (2D)- and three-dimensional speckle-tracking echocardiography (3D-STE) and (2) further investigate which strain parameter measured by 2D- and 3D-STE is the more robust predictor of MF in heart transplant (HT) recipients.Methods: A total of 40 patients with HT and 20 healthy controls were prospectively enrolled. Left ventricular (LV)-global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured by 2D- and 3D-STE. LV diffuse MF was defined by cardiovascular magnetic resonance (CMR)-ECV.Results: The HT recipients had a significantly higher native T1 and ECV than healthy controls (1043.8 ± 34.0 vs. 999.7 ± 19.7 ms, p &lt; 0.001; 26.6 ± 2.7 vs. 24.3 ± 1.8%, p = 0.02). The 3D- and 2D-STE-LVGLS and LVGCS were lower (p &lt; 0.005) in the HT recipients than in healthy controls. ECV showed a moderate correlation with 2D-LVGLS (r = 0.53, p = 0.002) and 3D-LVGLS (r = 0.60, p &lt; 0.001), but it was not correlated with 2D or 3D-LVGCS, or LVGRS. Furthermore, 3D-LVGLS and 2D-LVGLS had a similar correlation with CMR-ECV (r = 0.60 vs. 0.53, p = 0.670). A separate stepwise multivariate linear analysis showed that both the 2D-LVGLS (β = 0.39, p = 0.019) and 3D-LVGLS (β = 0.54, p &lt; 0.001) were independently associated with CMR-ECV.Conclusion: CMR marker of diffuse MF was present in asymptomatic patients with HT and appeared to be associated with decreased myocardial strain by echocardiography. Both the 2D- and 3D-LVGLS were independently correlated with diffuse LVMF, which may provide an alternative non-invasive tool for monitoring the development of adverse fibrotic remodeling during the follow-up of HT recipients.
Pediatric Acute Myocarditis With Short-Term Outcomes and Factors for Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study in Vietnam
Authors: Tuan Ta Anh , Xoay Tran Dang , Phuc Phan Huu , Hung Dau Viet , Dung Nguyen Trong , Truong Nguyen Ly Thinh , Thuan Nguyen Van , Dien Tran Minh 
Published: December 2021

Objective: Data on the management and outcomes of acute myocarditis treated with extracorporeal membrane oxygenation (ECMO) among low- and middle-income countries are limited. This study aimed to determine the short-term outcomes and also identify factors associated with ECMO use among children with acute myocarditis at a tertiary children's hospital in Vietnam.Methods: A single-center, retrospective observational study was conducted between January 2016 and February 2021. Pediatric patients with acute myocarditis, aged 1 month to 16 years, were included.Results: In total, 54 patients (male, 46%; median age, 7 years) with acute myocarditis were included; 37 of them received ECMO support. Thirty percent (16/54) of the patients died, and 12 of them received ECMO. Laboratory variables that differed between survivors and non-survivors included median left ventricular ejection fraction (LVEF) at 48 h (42 vs. 25%; p = 0.001), platelet count (304 g/L [interquartile range (IQR): 243–271] vs. 219 g/L [IQR: 167–297]; p = 0.014), and protein (60 g/dl [IQR: 54–69] vs. 55 [IQR: 50–58]; p = 0.025). Among patients who received ECMO, compared with the survivors, non-survivors had a low LVEF at 48 h (odds ratio (OR), 0.8; 95% confidence interval (CI): 0.6–0.9; p = 0.006) and high vasoactive-inotropic score (OR, 1.0; 95% CI: 1.0–1.0; p = 0.038) and lactate (OR, 2.8; 95% CI, 1.2–6.1; p = 0.013) at 24 h post-ECMO.Conclusions: The case fatality rate among children with acute myocarditis was 30 and 32% among patients requiring ECMO support. Arrhythmia was an indicator for ECMO in patients with cardiogenic shock.
Lower Masticatory Performance Is a Risk for the Development of the Metabolic Syndrome: The Suita Study
Authors: Fushida Shuri , Kosaka Takayuki , Nakai Michikazu , Kida Momoyo , Nokubi Takashi , Kokubo Yoshihiro , Watanabe Makoto , Miyamoto Yoshihiro , Ono Takahiro , Ikebe Kazunori 
Published: December 2021

Objectives: Declined masticatory function has recently been receiving attention as a risk factor for poor general health. The present longitudinal analysis was conducted to clarify the relationship between decreased masticatory performance and the development of the metabolic syndrome (MetS) in a general urban cohort in Japan.Methods: We surveyed 599 participants (254 men, 345 women; mean age at baseline, 65.8 ± 7.8 years) who underwent physical health checkups in the Suita study. We evaluated masticatory performance at baseline using test gummy jelly and divided participants into two groups: a “Lower group,” comprising participants in the lower 25% of the masticatory performance at baseline; and a “Normal group,” comprising all others. We estimated hazard ratios (HRs) for the Lower group by using Cox proportional hazard regression analysis to develop the MetS and the components of the MetS at follow-up, adjusting for age, smoking status, and periodontal status.Results: On Cox proportional hazard regression analysis, the multivariable adjusted hazard ratio for the development of the MetS in the Lower group was 2.24 (95% confidence interval, 1.12–4.50) in men. The multivariable adjusted hazard ratio for the development of high blood pressure was 3.12 (1.42–6.87), for high triglycerides was 2.82 (1.18–6.76), and for high fasting plasma glucose was 2.65 (1.00–7.00) in men.Conclusions: Lower masticatory performance suggested to be a risk factor for the development of the MetS as well as MetS components such as high blood pressure, high triglycerides, and high fasting plasma glucose in Japanese men.
Normalized Cardiac Structure and Function in COVID-19 Survivors Late After Recovery
Authors: Gao Yi-Ping , Zhou Wei , Huang Pei-Na , Liu Hong-Yun , Bi Xiao-Jun , Zhu Ying , Sun Jie , Tang Qiao-Ying , Li Li , Zhang Jun , Sun Rui-Ying , Cheng Xue-Qing , Liu Ya-Ni , Deng You-Bin 
Published: December 2021

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited.Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318–337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients.Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI).Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression
Authors: Feng Dan-dan , Zheng Bin , Yu Jing , Zhang Man-li , Ma Ying , Hao Xiao , Wen Jin-kun , Zhang Xin-hua 
Published: December 2021

Background: Intimal hyperplasia is a major complication of restenosis after angioplasty. The abnormal proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) are the basic pathological feature of neointimal hyperplasia. 17β-Estradiol can inhibit VSMCs proliferation and inflammation. However, it is still unclear whether and how 17β-Estradiol affects intimal hyperplasia.Methods: The neointima hyperplasia was observed by hematoxylin/eosin staining. The expression of PCNA, cyclin D1, NOX1, NOX4 and p47phox in neointima hyperplasia tissues and VSMCs was determined by qRT-PCR and Western blotting. MTS assay, cell counting and EdU staining were performed to detect cells proliferation. The oxidative stress was assessed by ROS staining.Results: 17β-Estradiol suppressed carotid artery ligation-induced intimal hyperplasia, which is accompanied by an increase of BHLHE40 level. Furthermore, loss- and gain-of-function experiments revealed that BHLHE40 knockdown promotes, whereas BHLHE40 overexpression inhibits TNF-α-induced VSMC proliferation and oxidative stress. 17β-Estradiol inhibited TNF-α-induced VSMC proliferation and oxidative stress by promoting BHLHE40 expression, thereby suppressing MAPK signaling pathways. In addition, enforcing the expression of BHLHE40 leads to amelioration of intimal hyperplasia.Conclusions: Our study demonstrates that 17β-Estradiol inhibits proliferation and oxidative stress in vivo and in vitro by promotion of BHLHE40 expression.
Animals for Tools: The Origin and Development of Bone Technologies in China
Authors: Ma Shuwen , Doyon Luc 
Published: December 2021

The origin and development of bone technologies in China are reviewed in the light of recent discoveries and compared to trends emerging from the European and African archaeological records. Three categories of osseous tools are targeted: 1) unmodified bone fragments bearing traces of use in technological activities; 2) bone fragments modified to a variable extent with techniques generally used in stone technologies; 3) osseous fragments entirely shaped with techniques fit for the manufacture of formal bone tools. Early evidence of bone technologies in China are sporadically found in contexts dated between 1.8 and 1.0 Ma. By the late MIS6–early MIS5, bone tools are well-integrated in the technological systems of Pleistocene populations and the rules guiding their use appear increasingly standardized. In addition, the first evidence for the use of osseous material in symbolic activities emerges in the archaeological record during this period. Finally, between 40 and 35 ka, new manufacturing techniques and products are introduced in Late Palaeolithic technological systems. It is first apparent in the manufacture of personal ornaments, and followed by the production and diversification of formal bone tools. By that time, population dynamics seem to become materialized in these items of material culture. Despite regional specificities, the cultural trajectories identified for the evolution of bone technologies in China seem entirely comparable to those observed in other regions of the world.
Deciphering the Irregular Risk of Stroke Increased by Obesity Classes: A Stratified Mendelian Randomization Study
Authors: Zou Xuelun , Wang Leiyun , Xiao Linxiao , Xu Zihao , Yao Tianxing , Shen Minxue , Zeng Yi , Zhang Le 
Published: December 2021

BackgroundTo investigate the relationship between different classes of obesity and stroke, we conducted a stratified Mendelian randomization (MR) study.MethodsThe body mass index (BMI) data of 263,407 Europeans with three classes of obesity (obesity class I, 30 kg/m2 ≤ BMI &lt; 35 kg/m2; obesity class II, 35 kg/m2 ≤ BMI &lt; 40 kg/m2; obesity class III, 40 kg/m2 ≤ BMI) were extracted from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary-level data of stroke and its subtypes [ischemic stroke (IS) and intracerebral hemorrhage (ICH)] were obtained from the genome-wide association study (GWAS) meta-analysis, which was performed by the MEGASTROKE consortium. MR methods were used to identify the causal relationships.ResultsThe MR analysis revealed that both obesity class I [odds ratio (OR) = 1.08, 95% CI: 1.05–1.12, p = 1.0 × 10-5] and obesity class II (OR = 1.06, 95% CI: 1.03–1.09, p = 1 × 10-4) were significantly positively related to IS, while obesity class III was not (OR = 1.01, 95% CI: 0.96–1.06, p = 0.65). In contrast to IS, there was no class of obesity associated with ICH risk. Further examination of the relationship between obesity classification and IS subtypes revealed that certain degrees of obesity were related to large artery stroke (LAS) (OR = 1.14, 95% CI: 1.04–1.24, p = 2.8 × 10-3 for class I; OR = 1.08, 95% CI: 1.01–1.16, p = 0.002 for class II) and cardioembolic stroke (CES) (OR = 1.11, 95% CI: 1.02–1.20, p = 0.02 for class I; OR = 1.08, 95% CI: 1.02–1.15, p = 0.007 for class II).ConclusionsA higher risk of IS, but not ICH, could be linked to obesity classes I and II. A strong association between LAS and CES and obesity was observed among all IS subtypes in the obese population.
Higher Triglyceride–Glucose Index Is Associated With Increased Likelihood of Kidney Stones
Authors: Qin Zheng , Zhao Junjie , Geng Jiwen , Chang Kaixi , Liao Ruoxi , Su Baihai 
Published: December 2021

AimsWe aimed to assess the association between triglyceride–glucose (TyG) index and kidney stones in US adults.MethodsData were obtained from the 2007–2014 National Health and Nutrition Examination Survey (NHANES). Participants aged ≥18 years who were not pregnant and provided complete data about TyG index and kidney stones were included in the analysis. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between TyG index and nephrolithiasis and recurrence.ResultsA total of 20,972 participants were included with the mean TyG index of 8.71 ± 0.72. The prevalence rates of nephrolithiasis and recurrence were 9.30% and 3.17% overall and increased with the higher TyG index tertiles (Nephrolithiasis: Tertile 1, 6.98%; Tertile 2, 9.15%; Tertile 3, 11.98%, p &lt; 0.01; Recurrence: Tertile 1, 1.84%; Tertile 2, 3.27%; Tertile 3, 4.50%, p &lt; 0.01). Each unit increase in TyG index was associated with 12% and 26% higher odds of nephrolithiasis [odds ratio (OR) = 1.12; 95% CI: 1.02–1.22; p = 0.02] and recurrence (OR = 1.26; 95% CI: 1.08–1.46; p &lt; 0.01). Interaction tests indicated no significant effect of gender, age, body mass index, hypertension, and diabetes on this association between TyG index and kidney stones.ConclusionsHigher TyG index was associated with an increased likelihood of nephrolithiasis and recurrence. Considering TyG index is a reliable indicator of insulin resistance (IR). Treatment and management of IR at a younger age may improve or alleviate the occurrence and recurrence of kidney stones.
Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
Authors: Zhu Jiahao , Zhao Huanling , Chen Dingwan , Tse Lap Ah , Kinra Sanjay , Li Yingjun 
Published: December 2021

BackgroundObservational studies have shown possible bidirectional association between type 2 diabetes (T2D) and pulmonary function, but the causality is not well defined. The purpose of this study is to investigate genetic correlation and causal relationship of T2D and glycemic traits with pulmonary function.MethodsBy leveraging summary statistics from large-scale genome-wide association studies, linkage disequilibrium score regression was first implemented to quantify genetic correlations between T2D, glycemic traits, and several spirometry indices. Then both univariable and multivariable Mendelian randomization analyses along with multiple pleiotropy-robust methods were performed in two directions to assess the causal nature of these relationships.ResultsForced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) showed significant genetic correlations with T2D and fasting insulin levels and suggestive genetic correlations with fasting glucose and hemoglobin A1c. In Mendelian randomization analyses, genetically predicted higher FEV1 (OR = 0.77; 95% CI = 0.63, 0.94) and FVC (OR = 0.82; 95% CI = 0.68, 0.99) were significantly associated with lower risk of T2D. Conversely, genetic predisposition to higher risk of T2D exhibited strong association with reduced FEV1 (beta = −0.062; 95% CI = −0.100, −0.024) and FEV1 (beta = −0.088; 95% CI = −0.126, −0.050) and increased FEV1/FVC ratio (beta = 0.045; 95% CI = 0.012, 0.078). We also found a suggestive causal effect of fasting glucose on pulmonary function and of pulmonary function on fasting insulin and proinsulin.ConclusionsThe present study provided supportive evidence for genetic correlation and bidirectional causal association between T2D and pulmonary function. Further studies are warranted to clarify possible mechanisms related to lung dysfunction and T2D, thus offering a new strategy for the management of the two comorbid diseases.
The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
Authors: Wang Ying , Xiao Xiao , Chen Shipeng , Huang Chenjun , Zhou Jun , Dai Erhei , Li Ya , Liu Lijuan , Huang Xianzhang , Gao Zhiyuan , Wu Chuanyong , Fang Meng , Gao Chunfang 
Published: December 2021

BackgroundThis study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.MethodA total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb− patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis.ResultsThe 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb− in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p &lt; 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg.ConclusionBased on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.
Competency-Based Education: Developing an Advanced Competency Framework for Indonesian Pharmacists
Authors: Meilianti Sherly , Smith Felicity , Bader Lina , Himawan Roy , Bates Ian 
Published: December 2021

Introduction: Pharmacists need to be adaptable, flexible, and capable of advancing their practice to adapt to rapidly changing population health needs. We describe an educational approach to pharmacy workforce transformation in Indonesia through an advanced practice competency framework development using an “adopt and adapt” methodology.Methods: The competency framework development process comprised a translation phase, an adopt and adapt phase, validation through a nationwide mapping survey, and a completion phase through leadership consensus panels. We conducted a forward-backwards translation of a previously validated Advanced to Consultancy Level Framework (ACLF) to yield the Indonesian Advanced Development Framework (IADF) draft. The subsequent adoption and adaptation process was conducted through a series of consensus panels. We validated the IADF through a nationwide workforce survey. The final phase included leadership consensus panels with the professional leadership body in Indonesia. We analyzed the qualitative data thematically and the quantitative data using a Multiple Correspondence Analysis (MCA) technique.Results: We identified conceptual challenges in adopting and adapting the existing ACLF, which were addressed by providing a national glossary and concrete examples. A total of 6,212 pharmacists participated in the national workforce survey, of which 43% had &lt;2 years of post-license (post-registration) experience. The MCA results showed that practitioner self-assessment to the IADF could discriminate their career development stages. The results also indicated a four-stage career model (including early years career training). Embedding this model in a structured national training program will enhance the professional workforce development through a more structured career journey.Conclusions: We describe the first validation of an advanced competency development framework for the pharmacy workforce in a non-Anglophone country, showing the possibility of transnational applicability of this framework. We argue that this methodology can be used in Low and Middle-income countries (LMICs) for the more rapid advancement of pharmaceutical care practice.
Boosting Natural Killer Cell Therapies in Glioblastoma Multiforme Using Supramolecular Cationic Inhibitors of Heat Shock Protein 90
Authors: Saha Tanmoy , van Vliet Amanda A. , Cui Chunxiao , Macias Jorge Jimenez , Kulkarni Arpita , Pham Luu Nhat , Lawler Sean , Spanholtz Jan , Georgoudaki Anna-Maria , Duru Adil Doganay , Goldman Aaron 
Published: December 2021

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood–brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays &gt;2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro. Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro. Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34+ hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate &gt;350% relative cell killing is achieved in SCI-101–treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM.