bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Nonalcoholic Steatohepatitis on a Chip
Authors: Freag May S. , Namgung Bumseok , Reyna Fernandez Maria E. , Gherardi Ermanno , Sengupta Shiladitya , Jang Hae Lin 
Published: November 2020

We developed a NASH-on-a-chip where human primary hepatocytes (HCs), Kupffer cells (KCs), and hepatic stellate cells (HSCs) were cultured in the 3D hydrogel scaffold, while a blood vessel mimetic endothelialized inlet channel was engineered using human liver sinusoidal endothelial cells (LSECs), via which the system was exposed to metabolic and inflammatory stressors. Exposing liver chips to a lipotoxic environment led to the gradual development of NASH phenotypic characteristics, including intracellular lipids accumulation, hepatocellular ballooning, HSC activation, and elevation of inflammatory and profibrotic molecular markers. We demonstrate that the NASH-on-a-chip can be used to test the efficacy of pharmacological agents to inhibit the development of NASH.
Nonalcoholic steatohepatitis (NASH), an advanced stage of nonalcoholic fatty liver disease (NAFLD), is a rapidly growing and global health problem compounded by the current absence of specific treatments. A major limiting factor in the development of new NASH therapies is the absence of models that capture the unique cellular structure of the liver microenvironment and recapitulate the complexities of NAFLD progression to NASH. Organ-on-a-chip platforms have emerged as a powerful approach to dynamically model diseases and test drugs. Herein, we describe a NASH-on-a-chip platform. Four main types of human primary liver cells (hepatocytes [HCs], Kupffer cells, liver sinusoidal endothelial cells, and hepatic stellate cells [HSCs]) were cocultured under microfluidic dynamics. Our chip-based model successfully recapitulated a functional liver cellular microenvironment with stable albumin and urea secretion for at least 2 weeks. Exposing liver chips to a lipotoxic environment led to gradual development of NASH phenotypic characteristics, including intracellular lipid accumulation, hepatocellular ballooning, HSC activation, and elevation of inflammatory and profibrotic markers. Further, exposure of the chip to elafibranor, a drug under study for the therapy of NASH, inhibited the development of NASH-specific hallmarks, causing an ˜8-fold decrease in intracellular lipids, a 3-fold reduction in number of ballooned HCs, a significant reduction in HSC activation, and a significant decrease in the levels of inflammatory and profibrotic markers compared with controls. Conclusion: We have successfully developed a microfluidic NASH-on-a-chip platform that recapitulates the main NASH histologic endpoints in a single chip and that can emerge as a powerful noninvasive, human-relevant, in vitro platform to study disease pathogenesis and develop novel anti-NASH drugs.
Knowledge of social distancing measures and adherence to restrictions during the COVID‐19 pandemic
Authors: Sturman Daniel , Auton Jaime C. , Thacker Jemma 
Published: November 2020

AbstractIssue addressedWith no efficacious treatments or vaccines available, social distancing measures remain the most effective approach for reducing the transmission of the COVID‐19 virus. However, adherence to social distance measures presumably requires knowledge and understanding of the current social distancing restrictions.MethodsA modified version of the Theory of Planned Behaviour examined the role of knowledge and understanding of current social distancing measures in predicting intentions to adhere to social distancing restrictions. An online survey was administered to respondents (N = 374) in Melbourne, Australia during a period of heightened social distancing restrictions. In addition to measuring respondents’ general intentions to adhere to restrictions, vignettes were used to assess intended behaviour in specific situations.ResultsKnowledge of social distancing restrictions predicted intentions to adhere in specific situations, but not general intentions to adhere. Knowledge of restrictions also predicted positive attitudes towards current restrictions and a greater perceived ability to adhere to the restrictions, while positive attitudes was a good predictor of both general and specific intentions to adhere.ConclusionsThe findings suggest that attitudes towards restrictions may influence whether individuals attempt to adhere to restrictions, but knowledge of the restrictions influences whether the intended behaviour actually adheres to current restrictions.So what?These outcomes indicate that members of the public should be educated regarding the negative consequences associated with the COVID‐19 virus and the capacity of social distancing to reduce transmission of the virus, and a need for social distancing restrictions to be uncomplicated and clearly communicated.
Data entry quality of double data entry vs automated form processing technologies: A cohort study validation of optical mark recognition and intelligent character recognition in a clinical setting
Authors: Paulsen Aksel , Harboe Knut , Dalen Ingvild 
Published: November 2020

AbstractBackground and AimsPatient‐reported outcome measures (PROMs) are increasingly used in health services. Paper forms are still often used to register such data. Manual double data entry (DDE) has been defined as the gold standard for transferring data to an electronic format but is laborious and costly. Automated form processing (AFP) is an alternative, but validation in a clinical context is warranted. The study objective was to examine and validate a local hospital AFP setup.MethodsPatients over 18 years of age who were scheduled for knee or hip replacement at Stavanger University Hospital from 2014 to 2017 who answered PROMs were included in the study and contributed PROM data. All paper PROMs were scanned using the AFP techniques of optical mark recognition (OMR) and intelligent character recognition (ICR) and were processed by DDE by health secretaries using a data entry program. OMR and ICR were used to capture different types of data. The main outcome was the proportion of correctly entered numbers, defined as the same response recorded in AFP and DDE or by consulting the original paper questionnaire at the data field, item, and PROM level.ResultsA total of 448 questionnaires from 255 patients were analyzed. There was no statistically significant difference in error proportions per 10 000 data fields between OMR and DDE for data from check boxes (3.52 95% confidence interval (CI) 2.17 to 5.72 and 4.18 (95% CI 2.68‐6.53), respectively P = .61). The error proportion for ICR (nine errors) was statistically significantly higher than that for DDE (two errors), that is, 3.53 (95% CI 1.87‐6.57) vs 0.78 (95% CI 0.22‐2.81) per 100 data fields/items/questionnaires; P = .033. OMR (0.04% errors) outperformed ICR (3.51% errors; P < .001), Fisher's exact test.ConclusionsOMR can produce an error rate that is comparable to that of DDE. In our setup, ICR is still problematic and is highly dependent on manual validation. When AFP is used, data quality should be tested and documented.
ATF4‐modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy
Authors: Wang Yan , He Shi‐Hao , Liang Xu , Zhang Xin‐Xin , Li Shan‐Shan , Li Tian‐Fang 
Published: November 2020

AbstractActivating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene‐delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum‐derived exosomes from OA mice as the gene‐delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury‐induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham‐Exo and OA‐Exo, respectively. ATF4‐overexpressing OA‐Exo (ATF4‐OA‐Exo) was developed by introducing ATF4 mRNA into OA‐Exo via electroporation. Four weeks after surgery, OA mice received intra‐articular injections of sham‐Exo, OA‐Exo, and ATF4‐OA‐Exo, respectively. The results showed that intra‐articular injection of ATF4‐OA‐Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra‐articular injection of ATF4‐OA‐Exo. Further in vitro assays revealed that ATF4‐OA‐Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF‐α‐ or tunicamycin‐treated chondrocytes. Together, ATF4‐modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.
Oxidized low‐density lipoprotein accelerates the injury of endothelial cells viacirc‐USP36/miR‐98‐5p/VCAM1axis
Authors: Peng Kuang , Jiang Peiyong , Du Yafang , Zeng Dianmei , Zhao Junbi , Li Meiling , Xia Chunchen , Xie Zhong , Wu Jie 
Published: November 2020

AbstractCircular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ‐ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low‐density lipoprotein (ox‐LDL). The levels of circ‐USP36, microRNA‐98‐5p (miR‐98‐5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real‐time polymerase chain reaction (qRT‐PCR). The viability, apoptosis and inflammation were detected by (4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme‐linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation‐related markers and VCAM1 protein level. The targets of circ‐USP36 and miR‐98‐5p were searched using starBase website, and dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox‐LDL exposure induced the upregulation of circ‐USP36 in HUVEC cells. Circ‐USP36 accelerated ox‐LDL‐induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR‐98‐5p was a direct downstream gene of circ‐USP36. Circ‐USP36 promoted the injury of ox‐LDL‐induced HUVEC cells through targeting miR‐98‐5p. VCAM1 could bind to miR‐98‐5p, and the protective effects of miR‐98‐5p accumulation on ox‐LDL‐induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ‐USP36/miR‐98‐5p signaling in HUVEC cells. Ox‐LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ‐USP36, thus elevating the expression of VCAM1 via miR‐98‐5p.
Parathyroid hormone ameliorates osteogenesis of human bone marrow mesenchymal stem cells against glucolipotoxicity through p38 MAPK signaling
Authors: Wang Yuli , Huang Lintong , Qin Ziyue , Yuan Hua , Li Bing , Pan Yongchu , Wang Xiaoqian , Du Xin , Hao Shushu , Du Yifei , Wang Ruixia , Shen Yi 
Published: November 2020

AbstractDiabetes mellitus (DM)‐induced glucolipotoxicity is a factor strongly contributing to alveolar bone deficiency. Parathyroid hormone (PTH) has been identified as a main systemic mediator to balance physiological calcium in bone. This study aimed to uncover PTH's potential role in ameliorating the osteogenic capacity of human bone marrow mesenchymal stem cells (HBMSCs) against glucolipotoxicity. Optimal PTH concentrations and high glucose and palmitic acid (GP) were administered to cells, followed by alkaline phosphatase (ALP) staining and ALP activity assay. Quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and Immunoblot were carried out for assessing mRNA and protein amounts, respectively. Cell counting kit‐8 (CCK‐8) and flow cytometry were performed for quantitating cell proliferation. Osteogenesis and oxidative stress were determined, and the involvement of mitogen‐activated protein kinase (MAPK) signaling was further verified. About 1–50 mmol/ml GP significantly inhibited the osteogenic differentiation of HBMSCs. 10−9 mol/L PTH was found to be the optimal concentration for HBMSC induction. PTH had no effects on HBMSC proliferation, with or without GP treatment. PTH reversed inadequate osteogenesis and excessive oxidative stress in GP‐treated HBMSCs. Mechanistically, PTH activated p38 MAPK signaling, while inhibiting p38 MAPK‐suppressed PTH's beneficial impacts on HBMSCs. Collectively, PTH promotes osteogenic differentiation in HBMSCs against glucolipotoxicity via p38 MAPK signaling.
Facilitation Literacy: Circulating Power in Professional Learning Conversations With Teacher Colleagues
Authors: Lillge Danielle 
Published: November 2020

AbstractThe author describes how and why a team of literacy leaders fruitfully studied their own efforts to address the challenges they faced in supporting teacher colleagues’ learning and teaching. Actively resisting facilitation models that privilege facilitators’ power to fix colleagues’ dilemmas and consistent with their belief that professional learning is socially constructed, the facilitators adopted a view of power as a resource that, when circulated, offers people opportunities to be who they wish, and be seen as knowledgeable without challenge. To explore ways of circulating power, the facilitators studied transcripts of their interactions with colleagues. Through co‐analysis of their transcripts, the team identified five discursive strategies supporting circulation of power: identifying sticking points, listening, posing clarifying questions, reframing the challenge, and soliciting feedback. The facilitators’ efforts to circulate power cultivated generative social and discursive spaces, which afforded their colleagues opportunities to negotiate self‐identified dilemmas to advocate for themselves and their students’ literacy learning.
A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations
Authors: Yau Michelle S , Kuipers Allison L , Price Ryan , Nicolas Aude , Tajuddin Salman M , Handelman Samuel K , Arbeeva Liubov , Chesi Alessandra , Hsu Yi-Hsiang , Liu Ching-Ti , Karasik David , Zemel Babette S , Grant Struan FA , Jordan Joanne M , Jackson Rebecca D , Evans Michele K , Harris Tamara B , Zmuda Joseph M , Kiel Douglas P 
Published: November 2020

ABSTRACT
Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index &gt;60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10−4), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10−4) and 7q31 (WNT16, p = 2.96 × 10−5), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p &lt; 2.23 × 10−4), 11q14 (DCDC5, p &lt; 5.35 × 10−5), and 17p13 (SMG6, p &lt; 6.78 × 10−5) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10−2), MBL2 (p = 4.09 × 10−2), MEPE (p = 3.15 × 10−2), SLC25A13 (p = 3.03 × 10−2), STARD3NL (p = 3.35 × 10−2), and TNFRSF11A (p = 3.18 × 10−3) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).
Impact of Genetic and Pharmacologic Inhibition of Myostatin in a Murine Model of Osteogenesis Imperfecta
Authors: Omosule Catherine L , Gremminger Victoria L , Aguillard Ashley M , Jeong Youngjae , Harrelson Emily N , Miloscio Lawrence , Mastaitis Jason , Rafique Ashique , Kleiner Sandra , Pfeiffer Ferris M , Zhang Anqing , Schulz Laura C , Phillips Charlotte L 
Published: November 2020

ABSTRACT
Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-β superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild–moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).
Ferritin as a key risk factor for nonalcoholic fatty liver disease in children with obesity
Authors: Zhang Junfeng , Cao Jiajia , Xu Hui , Dong Guanping , Huang Ke , Wu Wei , Ye Jingjing , Fu Junfen 
Published: November 2020

AbstractBackgroundThe association between serum ferritin and nonalcoholic fatty liver disease (NAFLD) in children with obesity is not clear. This study was designed to investigate whether serum ferritin can be an independent predictor for NAFLD.MethodsAccording to the hepatic ultrasound results, a total of 347 children with obesity were enrolled in this study. Among them, 95 patients with NAFLD and 95 without NAFLD were matched for gender, age, blood pressure and body mass index, the odds ratios (OR) and 95% confidence intervals (CI) for the association of ferritin and the risk of NAFLD were analyzed.ResultsAfter propensity score matching, ferritin values of the patients with NAFLD were significantly higher than those without NAFLD group. Alanine aminotransferase and ferritin were strongly associated with NAFLD in multivariate stepwise logistic regression analysis. The medium and high levels of ferritin increased risk of NAFLD, and the adjusted ORs were 3.298 (95% CI:1.326‐8.204), 7.322 (95% CI:2.725‐19.574) across the ferritin concentration tertiles after adjustment for confounders. Ferritin was shown to be the best predictor for NAFLD with sensitivity and specificity of 60.0% and 77.9%, respectively, area under the curve was 0.733.ConclusionThe results show that serum ferritin can usefully be considered as a predictor of NAFLD in children with obesity.
Current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced ejection fraction: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Ishibashi Kohei , Kabutoya Tomoyuki , Yoshiga Yasuhiro , Kohno Ritsuko , Abe Haruhiko , Nogami Akihiko ,   Members of the Implantable Cardioverter‐Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: November 2020

AbstractBackgroundThe aim of this study was to clarify the current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced left ventricular ejection fraction (LVEF).MethodsThe follow‐up data of the Japan cardiac device treatment registry (JCDTR) was analyzed in 746 patients with LVEF ≦35% and no prior history of sustained ventricular arrhythmias who underwent de novo implantable cardioverter‐defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT‐D) implantation between January 2011 and August 2015.ResultsElectrophysiological study (EPS) with programmed ventricular stimulation had been performed before the device implant in 118 patients (15.8%, EPS group). During the mean follow‐up of 21 ± 12 months, the rate of freedom from any death and appropriate defibrillator therapy was not significantly different between EPS group (n = 118) and No EPS group (n = 628). NYHA class II‐IV, and QRS duration were negatively associated with performing EPS. Among patients in the EPS group, the rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) induction was 48%. The inducibility was not a predictor of appropriate defibrillator therapy, whereas BNP ≧535 pg/mL and no use of amiodarone were significantly associated with a risk of the appropriate therapy.ConclusionEPS for induction of VT/VF had been performed in about 16% of patients with reduced LVEF before primary prevention ICD/CRT‐D implantation. Elevated BNP levels and no use of amiodarone, but not inducibility of VT/VF, appeared to be associated with appropriate defibrillator therapy in these populations.