bluuebunny/crossref_metadata_2025 huggingface dataset:
Rbm24 Displays Dynamic Functions Required for Myogenic Differentiation During Muscle Regeneration
Authors: Grifone Raphaëlle , Saquet Audrey , Desgres Manon , Sangiorgi Claudia , Gargano Caterina , Li Zhenlin , Coletti Dario , Shi De-Li
Published: December 2020

Skeletal muscle has a remarkable capacity of regeneration after injury, but the cellular behavior and the regulatory network coordinating different steps of this repair process remain elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and are implicated in the maintenance of tissue homeostasis and plasticity. Rbm24 is required for myogenic differentiation during early development, but its function in adult muscle is open for investigation. Here we show that it exerts dynamic functions during muscle regeneration in mice. Consistent with its dynamic subcellular localization during embryonic muscle development, Rbm24 also displays cytoplasm to nucleus translocation during the differentiation of C2C12 myoblasts. In adult mice, Rbm24 mRNA is highly expressed in slow-twitch muscles, and Rbm24 protein is restricted to the myonucleus of myofibers. Upon injury, Rbm24 protein is upregulated in regenerating myofibers and rapidly accumulates in the myonucleus of nascent myofibers. By using satellite cell transplantation, we find that Rbm24 functions sequentially to regulate the differentiation of myofibers and the regeneration of damaged tissues. It is required for myogenin mRNA expression at early stages of muscle injury and for muscle-specific pre-mRNA alternative splicing at late stages of regeneration. These results identify Rbm24 as a multifaceted regulator of myoblast differentiation and function. They also provide insights into the molecular pathway orchestrating the expression of myogenic factors and muscle functional proteins during regeneration.
COVID-19 Associated Mortality and Cardiovascular Disease Outcomes Among U.S. Women Veterans
Authors: Tsai Shirling , Nguyen Hang , Ebrahimi Ramin , Barbosa Monica , Ramanan Bala , Heitjan Daniel , Hastings Jeffrey , Modrall John , Jeon-Slaughter Haekyung
Published: December 2020

BackgroundThe burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. MethodsWe conducted a case-control cohort study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We drew data from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020. Kaplan-Meier curves and the Cox proportional hazards model were employed to examine the distribution of time to death and the effects of baseline predictors on mortality risk. Generalized linear models were used to examine 60-day cardiovascular disease outcomes. Covariates studied included age, body mass index (BMI), and active smoking status at index, and pre-existing conditions of diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and a history of treatment with antiplatelet or anti-thrombotic drug at any time in the 2 years prior to the index date.ResultsWomen veterans who tested positive for SARS-CoV-2 had 4 times higher mortality risk than women veterans who tested negative (Hazard Ratio 3.8, 95% Confidence Interval CI 2.92 to 4.89) but had lower risk of cardiovascular events (Odds Ratio OR 0.78, 95% CI 0.66 to 0.92) and developing new heart disease conditions within 60 days (OR 0.67, 95% CI 0.58 to 0.77). Older age, obesity (BMI > 30), and prior CVD and COPD conditions were positively associated with increased mortality in 60 days. Despite a higher infection rate among minority women veterans, there was no significant race difference in mortality, cardiovascular events, or onset of heart disease. Conclusions and RelevanceSARS-CoV-2 infection increased short-term mortality risk among women veterans similarly across race groups. However, there was no evidence of increased cardiovascular disease incidence in 60 days. A longer follow-up of women veterans who tested positive is warranted.
Study on Influencing Factors to HIV Health Services Among MSM: Based on Andersen Behavioral Model
Authors: Lin Bing , Zhong Xiaoni , Ma Yingjie , Pan Hong , Dai Jianghong , Liang Hao , Huang Ailong
Published: December 2020

Background: We assessed the utilization of HIV health services and its influencing factors on consistent condom use, HIV testing and HIV counseling among men who have sex with men (MSM), so as to provide a theoretical basis for future infectious disease prevention and control strategies and health services policy formulation. Methods: This study is a cross-sectional study. From April 2013 to October 2014, a sample survey was conducted in southwest China including Chongqing, Sichuan, Xinjiang and Guangxi, and an anonymous self-administered questionnaire survey was conducted among MSM who met the requirements and were recruited. Based on Anderson Behavioral Model, the questionnaire divided the influencing factors into predisposing factor, enabling factor and need factor. There were 1727 valid questionnaires. SAS 9.4 was used for univariate analysis and multivariate Logistic regression analysis to explore the factors influencing the utilization of health services. AMOS Graphics 24.0 was used to construct the path diagram through path analysis to explore the effect among various factors. Results: In the survey of HIV health services, 9.96% of respondents consistently used condoms, 78.00% had HIV testing, and 60.63% had HIV counseling. Among the predisposing factor, the older respondents are, the easier it is to be tested for HIV(β=0.078, p＜0.001). Among the enabling factor, urban registration is a factor that promotes HIV testing and counseling(β=0.064,p=0.003 and β=0.072, p=0.002). Among the need factor, HIV knowledge score is also a key point affecting testing and counseling(β=0.157, p＜0.001 and β=0.184, p＜0.001). The diagnosis of STD can promote respondents counseling(β=0.051, p=0.031). Depression is a contributing factor to consistent condom use(β=0.051,p=0.033), but negative to HIV counseling(β=-0.119, p＜0.001). Conclusions: For these groups, MSM with high-risk characteristics should be identified as a priority in the future public health services. HIV knowledge should be promoted in health education, physical and mental health diagnosis and treatment should also be strengthened.
Survey Analysis to Determine the Impact of Evidence Informed Practice Education upon Faculty Clinical Instruction and East Asian Medicine Student’s Skills, Knowledge, Attitudes and Behaviors
Authors: Anderson Belinda , Dudla Sai , Marantz Paul , Kligler Benjamin , Leininger Brent , Evans Roni
Published: December 2020

BackgroundBetween 2013-2018 Pacific College of Health and Science (formerly Pacific College of Oriental Medicine) trained faculty and developed curriculum in evidence informed practice (EIP), with support from a grant from the National Institutes of Health (NIH). A three-credit (45 hour) Foundations of EIP course, and online EIP learning modules (developed as part of a previous NIH R25 award), were used for faculty and student training. In addition, EIP was incorporated into 73% of the East Asian medicine degree program. Clinical integration of EIP in the College clinic was enhanced by improving access to reference sources, including additional EIP-related questions to the patient intake forms, requiring the use of a patient-centered outcome instrument, and assessing student’s clinical EIP competencies. MethodsMaster’s degree student’s EIP skills, knowledge, attitudes and behaviors were assessed before and after taking the Foundations of EIP course using a 17-question paper-based survey with an additional open-ended comments section. The survey was administered in 29 courses across all three Pacific College campuses. Clinical faculty EIP instruction was evaluated on the New York City campus using a paper-based survey before and after changes were made to enhance the clinical integration of EIP. ResultsA total of 1181 completed EIP-course surveys consisting of 657 pre-EIP course surveys and 524 post-EIP course surveys were analyzed. There was a statistically significant improvement in student’s EIP skills, knowledge and behaviors after completing the EIP course. Students’ perception of the importance of EIP was high before and after the EIP course. Little change in Faculty’s EIP-related clinical instruction was evident following the EIP-related changes that were made to the Clinic. Conclusion Students’ self-assessed EIP skills, knowledge and behaviors improved after EIP training. Different approaches may be required to improve implementation of EIP in clinical settings.
Structural Inequities in Seasonal Influenza Vaccination Rates
Authors: Brewer Lara , Ommerborn Mark , Nguyen Augustina , Clark Cheryl
Published: December 2020

BackgroundInfluenza immunization is a highly effective method of reducing illness, hospitalization and mortality from this disease. However, influenza vaccination rates in the U.S. remain below public health targets. MethodsWe analyzed correlates of influenza vaccination rates using the 2019 Behavioral Risk Factor Surveillance System (BRFSS) in the year 2020. Our analysis compared influenza vaccination as the outcome of interest with the variables age, sex, race, education, income, geographic location, health insurance status, access to primary care, and history of delaying care due to cost.ResultsOur results showed that several persistent structural inequities predict influenza vaccination, within and across racial and ethnic groups, including geographic location, health insurance status, regular access to primary care, and the need to delay medical care due to cost.ConclusionWith the impending rollout of a COVID-19 vaccine, it is important for physicians and policymakers to recognize and eliminate structural racism and inequities in U.S. influenza vaccination rates so that future vaccination campaigns are not impeded by these barriers to immunization.
IGF-2 Modified by the m6A Demethylation Enzyme ALKBH5 in the Ossification of the Ligamentum Flavum
Authors: Kuang Ming-jie , Wang Hai-Feng , Qiu Jie , Wang An-bang , Wang Feng , Tan Bing-yi , Han Shi-jie , Li Xiao-ming , Wang Da-Chuan
Published: December 2020

Background: Ossification of the ligamentum flavum (OLF) is a pathological heterotopic ossification of the paravertebral ligament. However, the specific pathophysiology mechanism of this disease is still unknown. The m6A methylation and its potential functions in OLF remain to be unexplored. Method: In this study, we performed a transcriptome-wide methylation analysis using the OLF and normal ligaments to explore the mechanism of OLF. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. We screened out the methylase-ALKBH5, and by promoting or inhibiting its expression, observing the content of m6A, and measuring the ossification of ligaments, and then measuring IGF expression situation by alizarin red staining, alkaline phosphatase, immunofluorescence, immunohistochemistry, etc. Result: MeRIP-seq and qPCR showed that the m6A methylation level of OLF group was usually higher than that of control group. In addition, we found that ALKBH5 is an important demethyltransferase in OLF, which promotes the expression of m6A. ALKBH5 promotes the expression of IGF-2, which in turn promotes osteogenesis in OLF.Conclusion: Overall, we provided a region-specific map of m6A methylation and characterized the distinct features of specific and common methylation in OLF, and we proved that IGF-2 can be regulated by ALKBH5 to promote the process of OLF.
Serial Serum Creatinine and Urinary Acute Kidney Injury Biomarker Measurements in Dogs Envenomated by the European Adder (Vipera Berus).
Authors: Harjen Hannah , Nicolaysen Tove , Negard Tale , Lund Hege , Sævik Bente , Anfinsen Kristin , Moldal Elena , Zimmer Karin , Rørtveit Runa
Published: December 2020

Background Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 hours after bite, as well as 14 days later, using sCr and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs.Results Thirty-five envenomated dogs and 37 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Compared to controls, urinary albumin /uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1 /uCr were significantly elevated 12 hours (p < 0.001, p< 0.001, p = 0.01), 24 hours (p < 0.001, p < 0.001, p = 0.003) and 36 hours ( p < 0.001, p< 0.001, p = 0.001) after bite. Osteopontin /uCr was higher 24 and 36 hours after bite (p < 0.001), kidney injury molecule-1 /uCr, interleukin-8 /uCr and γ- glutamyl transferase /uCr were significantly higher 36 hours after bite (p = 0.0007, p = 0.0005, p= 0.001). Urinary cystatin C /uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls. Conclusion Urinary biomarker/Cr ratios are indicative of transient non-azotaemia AKI in dogs envenomated by V. berus.
Literacy as Part of Professional Knowing in a Swedish Dental Education  
Authors: Lindberg Viveca , Jounger Sofia Louca , Christidis Maria , Christidis Nikolaos
Published: December 2020

Background: Academic reading and writing are seen as self-evident literacy competences in most contemporary higher educations, and professional literacy is no exception for dental work. The purpose of this study was to analyze a Swedish dental programme, with respect to its design, in relation to content of relevance for academic and professional literacy. Secondarily, to identify and analyze what these students are expected to read and write, and what they write.Methods: Data, for this ethnographically inspired case-study, was produced by observations and audio-recordings of lectures, copies of teachers’ handouts and of volunteering students’ notes, and a multiple-choice-test. Data-analysis was made in five steps, starting with macro-level data, i.e. curriculum and syllabuses, followed by the syllabuses for the two observed modules, the teacher-provided material, analysis of the students’ notes, while in the fifth and final step, the results from the previous steps were compared, to find patterns of what students were expected to read and write, and what in the teacher-provided multimodal material that was emphasized in teachers’ talk.Results: This study showed that students were engaged in literacy events of reading, finding and watching videos on their learning platform, writing, and following instructions. Recurrent academic content comprised anatomy, physiology and pathology, while professional content comprised patient communication and anamnesis. Integrated content was initiated in teacher-constructed PowerPoints and by student-questions. Notetaking patterns varied between individual students, but the general pattern discerned for the group of students who shared their notes with us were complementary notes, to make available further descriptions of teacher-constructed text, and independent text describing pictures shown on teachers’ PowerPoints.Conclusion: Findings from this study indicate that academic literacy in dental education has a professional basis for reading, writing, and communicative purposes. The study also showed that academic and professional literacy were closely connected through recurrent integration.
NAT2 genetic polymorphism and age dependent efficacy of neurotropin® for the enhancement of aggrecan gene expression in nucleus pulposus cells
Authors: Nakai Tomoko , Sakai Daisuke , Nakamura Yoshihiko , Horikita Natsumi , Matsushita Erika , Naiki Mitsuru , Watanabe Masahiko
Published: December 2020

Background
Intervertebral disc degeneration, one of the major causes of low-back pain, results from altered biosynthesis/turnover of extracellular matrix in the disc. Previously, we reported that the analgesic drug Neurotropin® (NTP) had an anabolic effect on glycosaminoglycan synthesis in cultured nucleus pulposus (NP) cells via the stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1. However, its effect on the aggrecan core protein was not significantly detected, because of the data variance. A microarray analysis suggested that the effect of NTP on aggrecan was correlated with N-acetyltransferase 2 (NAT2), a drug-metabolizing enzyme. Specific NAT2 alleles are known to correlate with rapid, intermediate, and slow acetylation activities and side effects of various drugs. We investigated the association between the efficacy of NTP on aggrecan expression and the NAT2 genotype in cell donors.
Methods
NP cells were isolated from intervertebral disc tissues donated by 31 Japanese patients (28–68 years) who underwent discectomy. NTP was added to the primary cell cultures and its effect on the aggrecan mRNA was analyzed using real-time quantitative PCR. To assess acetylator status, genotyping was performed based on the inferred NAT2 haplotypes of five common single-nucleotide polymorphisms using allele-specific PCR.
Results
The phenotype frequencies of NAT2 in the patients were 0%, 42.0%, and 58.0% for slow, intermediate, and rapid acetylators, respectively. The proportions of responders to NTP treatment (aggrecan upregulation, ≥1.1-fold) in the intermediate and rapid acetylators were 76.9% and 38.9%, respectively. The odds ratio of the comparison of the intermediate acetylator status between responders and nonresponders was 5.2 (95% CI, 1.06–26.0, P = 0.036), and regarding the 19 male patients, this was 14.0 (95% CI, 1.54–127.2, P = 0.012). In the females, the effect was not correlated with NAT2 phenotype, but was negatively correlated with age (r = − 0.773, P = 0.006).
Conclusions
An intermediate acetylator status significantly favored the efficacy of NTP treatment to enhance aggrecan production in NP cells. In males, this tendency was detected with higher significance. Sex and age were also implicated in NTP efficacy. This study provides evidence of the association between NAT2 variants and the efficacy of NTP treatment.
Preparation and Characterization of Paclitaxel Palmitate Albumin Nanoparticles With High Loading Efficacy: an in Vitro and in Vivo Anti-tumor Study in Mouse Models
Authors: Chen Hang , Huang Sifan , Wang Heyi , Chen Xinmei , Zhang Haiyan , Xu Youfa , Fan Wei , Pan Yun , Wen Qiuyan , Lin Zhizhe , Wang Xuena , Gu Yongwei , Ding Baoyue , Chen Jianming , Wu Xin
Published: December 2020

Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.
Study on the Therapeutic Effects of Traditional Chinese Medicine on Insulin Resistance in Obese Mice by Modulating Intestinal Function
Authors: Ma Lirong , Bai Yongquan , Wang Wenwen , Shi Rui , Wang Furong , Liu Jun , Liu Chaoyang , Deng Hui , Xu Qing , Wenli Zhang , Guo Chen , Lu Zifan
Published: December 2020

Background: Obesity, in particular with the excessive visceral fat distribution which accompanied by several alterations at hormonal, inflammatory and endothelial level, was great to the detriment to human health. Although there were many treatments for obesity, most of them fail to had a radical effect or were accompanied with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipids, and inflammation were considered to be effective. Based on previous research, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were eventually selected to form an innovative herbal formula.Methods: The anti-inflammatory and lipid-lowering effects of the TCM were evaluated in an obese mouse models fed with a high-fat diet, and the effects of the TCM on the intestinal flora were further investigated.Results: The weights and insulin resistant of mice, as well as the inflammation, decreased after treatment. At the same time, the lipid metabolism increased after the mice were gavage with the TCM formula for 2 weeks. The intestinal motility of mice in the drug administration group was enhanced, and the intestinal flora was partially restored.Conclusion: In summary, our innovative Chinese herbal formula could significantly reduce the weight of obese mice, reduce the intestinal inflammation, improve intestinal motility, and improve the lipid metabolism in mice. Furthermore, the innovative formular could effectively prevent relevant metastasis diseases induced by obesity in mice.
Neutral Theory: Applicability and Neutrality of Using Generic Health-related Quality of Life Tools in Diseases or Conditions Where Specific Tools Are Available
Authors: Jandhyala Ravi
Published: December 2020

Background:Health-related quality of life (HRQoL) tools are limited by the indicators included in the construct and variation in interpretation by different researchers. Neutral Theory describes the ideal construct that includes all relevant indicators and, therefore, complete accuracy, or Neutrality. Neutral Theory can thereby provide the framework to develop or test constructs. To assess the application of Neutral Theory, the Neutrality of generic tools (SF-36 and EQ-5D) at measuring HRQoL was compared to disease/condition-specific tools, with the latter considered surrogates for the Neutral construct. Methods:Full descriptions of all disease/condition-specific HRQoL tools published on PubMed (to 01-Jul-19) were sourced. For each tool, the number of items with and without a direct match within the SF-36 and EQ-5D was recorded and the sensitivity/specificity calculated. Results:The SF-36 and EQ-5D did not achieve a sensitivity/specificity both >50% against any of the 163 disease/condition-specific tools identified. At 20% prevalence of poor HRQoL, the false positive rate (FPR) was >75% for all but two tools against the SF-36 and six tools against the EQ-5D. Increasing poor HRQoL to 80%, 47 tools for the SF-36 and 48 tools for the EQ-5D had a FPR <50%. For rare disease tools (<1/2,000 population; n=17), sensitivity/specificity ranged from 0-40%/5-31% for the SF-36 and 0-22%/29-100% for the EQ-5D. For non-rare (n=75) and symptom-specific tools (n=71) sensitivity/specificity was: 0-100%/0-100% (SF-36) and 0-50%/0-100% (EQ-5D); and 0-60%/0-19% (SF-36) and 0-25%/0-100% (EQ-5D), respectively. No concordance was recorded for 18% (2/11) of results from studies of rare disease tools versus the SF-36 (no data vs EQ-5D). For non-rare, disease-specific tools, results were discordant for 30% (25/84) and 35% (23/65) of studies against the SF-36 and EQ-5D, respectively. For symptom-specific tools, corresponding results were 36% (24/66) and 16% (5/31).Conclusions:Generic HRQoL tools appear poorly correlated with disease/condition-specific tools, which indicates that adoption of Neutral Theory in the development and assessment of HRQoL tools could improve their relevance, accuracy, and utility in economic evaluations of health interventions.
Inter-Vendor Performance of Deep Learning in Segmenting Acute Ischemic Lesions on Diffusion-Weighted Imaging: A Multicenter Study
Authors: Alis Deniz , Yergin Mert , Alis Ceren , Topel Cagdas , Asmakutlu Ozan , Bagcilar Omer , Senli Yeseren , Ustundag Ahmet , Salt Vefa , Dogan Sebahat , Velioglu Murat , Selcuk Hakan , Kara Batuhan , Oksuz Ilkay , Kizilkilic Osman , Karaarslan Ercan
Published: December 2020

There is little evidence on the applicability of deep learning (DL) in segmentation of acute ischemic lesions on diffusion-weighted imaging (DWI) between magnetic resonance imaging (MRI) scanners of different manufacturers. We retrospectively included DWI data of patients with acute ischemic lesions from six centers. Dataset A (n=2986) and B (n=3951) included data from Siemens and GE MRI scanners, respectively. The datasets were split into the training (80%), validation (10%), and internal test (10%) sets and six neuroradiologist created ground-truth masks. Models A and B were the proposed neural networks trained on datasets A and B and also fine-tuned across the datasets using their validation data. Another radiologist performed the segmentation on the test sets for comparisons. The median Dice scores of models A and B were 0.858 and 0.857 for the internal tests, which were non-inferior to the radiologist’s performance, but demonstrated lower performance than the radiologist on the external tests. Fine-tuned models A and B achieved median Dice scores of 0.832 and 0.846, which were non-inferior to the radiologist's performance on the external tests. The present work shows that inter-vendor operability of deep learning for the segmentation of ischemic lesions on DWI might be enhanced via transfer learning; thereby, their clinical applicability and generalizability could be improved.
High Cytoplasmic and Membranous Versus Nuclear Talin-1 Expression Associated With Malignancy Potential and Determine Survival and Metastasis of Clear Cell Renal Cell Carcinoma
Authors: Zanjani Leili Saeednejad , Vafaei Somayeh , Abolhasani Maryam , Fattahi Fahimeh , Madjd Zahra
Published: December 2020

Background: Talin-1 as a cytoskeleton protein participates in cell migration and has an essential role in cell adhesion, proliferation, tumorigenesis, invasion, and metastasis in various types of malignancies.Methods: Bioinformatics analysis has been performed by a using protein-protein interaction network, analyses among PRIDE databases, and indicated that Talin-1 protein as a potential prognostic focal adhesion factor in renal cell carcinoma (RCC). We, therefore, examined the protein expression levels and prognostic significance of Talin-1 with clinical follow-up in a total of 269 formalin-fixed paraffin-embedded tissue specimens from three important subtypes of RCC undergone radical nephrectomy and 30 adjacent normal tissues in three levels including, membrane, cytoplasm, and nucleus using immunohistochemistry on tissue microarrays. Then, we used a combined analysis with B7-H3 to confirm that Talin-1 may be related to metastasis.Results: The results showed that the expression of Talin-1 is significantly upregulated in most RCCs compared to adjacent normal tissues in protein levels. Further, there was a statistically significant difference between the membranous and cytoplasmic expression of Talin-1 and different subtypes of RCC (P < 0.001, P = 0.003, respectively). High membranous and cytoplasmic expression of Talin-1 was significantly associated with advanced nucleolar grade (P < 0.001, all), microvascular invasion (P = 0.007, P = 0.004), histological tumor necrosis (P = 0.020, P = 0.018), and invasion to Gerota’s fascia (P = 0.025, P = 0.050) in clear cell RCC (ccRCC). In addition, high membranous and cytoplasmic expression of Talin-1 was associated with significantly poorer disease-specific survival (DSS) (P = 0.043, P = 0.024, respectively) and progression-free survival (PFS) (P = 0.046, only in cytoplasmic expression). The co-expression of cytoplasmic Talin-1High /B7-H3High was observed to be associated with more aggressive tumor behavior and metastasis. Moreover, increased cytoplasmic expression of Talin-1High/B7-H3High compared to the other phenotypes was associated with poor prognosis and progression of the disease in patients with distant metastasis. Conclusion: Collectively, these observations indicate that Talin-1 is an important molecule involved in the spread and progression of ccRCC when expressed particularly in the cytoplasm and may serve as a novel prognostic biomarker in ccRCC if follow up time more prolonged.
Circular RNA circASPM Promotes the Progression of Glioblastoma by Acting as a Competing Endogenous RNA to Regulate miR-130b–3p/E2F1 Axis
Authors: Hou Dianqi , Wang Zhenlin , Li Haimeng , Liu Juan , Liu Yaohua , Jiang Yang , Lou Meiqing
Published: December 2020

background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.
Acidified Pepsin Promotes Laryngeal Precancerosis by Upregulating H+/K+-ATPase and Activating Mitophagy in Laryngeal Epithelial Cells
Authors: Cheng Ke-Jia , Xu Qiong , Li Zhi-Mei , Zhou Shui-Hong , Bao Yang-Yang , Chen Zhe , Fan Jun
Published: December 2020

Background: Although laryngopharyngeal reflux (LPR) has been implicated in various upper aerodigestive tract and laryngeal diseases, the underlying mechanisms remain elusive. In this study, we investigated the role of gastric acidified pepsin in laryngeal precancerosis. Results: Acidified pepsin (pH=3) enhanced the growth and survival of mouse laryngeal epithelial cells in vitro and promoted laryngeal mucosal thickening and laryngeal epithelial cell growth in vivo. Furthermore, acidified pepsin promoted autophagy/mitophagy induction, accompanied by a significant decrease in mitochondrial membrane potential (MMP). Inhibition of autophagy by chloroquine abolished the ability of acidified pepsin to promote mitophagy and cell growth in laryngeal epithelial cells. Additionally, chloroquine promoted cell apoptosis and further reduced MMP in laryngeal epithelial cells treated with acidified pepsin. The expression levels of pepsin and H+/K+-ATPase α and β subunits in 31 human laryngeal mucosa specimens were 51.6%, 48.4%, and 48.4%, respectively. Importantly, the pepsin level was correlated with the H+/K+-ATPase β subunit level. H+/K+-ATPase upregulation in laryngeal epithelial cells in response to acidified pepsin was essential for the mitophagy-promoting effect of acidified pepsin. H+/K+-ATPase knockout or inhibition further reduced MMP in the presence of acidified pepsin. Conclusions: Our findings suggest that in an acidic environment, pepsin promotes laryngeal epithelial cell growth and survival by upregulating H+/K+-ATPase and activating mitophagy, potentially leading to laryngeal precancerosis.
Effects of Empagliflozin in Different Phases of Diabetes Mellitus-Related Cardiomyopathy
Authors: Oka Satoshi , Kai Takahiko , Hoshino Katsuomi , Watanabe Kazunori , Nakamura Jun , Abe Makoto , Watanabe Akinori
Published: December 2020

Background: In diabetes mellitus-related cardiomyopathy (DMCMP), hyperglycemia causes endothelial dysfunction, fibrosis, and myocardial injury, which result in left ventricular (LV) dysfunction. Treatment with sodium–glucose co-transporter 2 inhibitor (SGLT2i) reduces the risk of exacerbation of heart failure (HF). The beneficial effects of SGLT2i on HF depend not only on indirect actions such as osmotic diuresis but also direct actions on the myocardium leading to improvements in LV function. However, it remains unclear whether SGLT2i treatment is equally effective in any phase of DMCMP. The aim of this observational study was to compare the efficacy of SGLT2i treatment on LV dysfunction between early and advanced DMCMP.Methods: Thirty-five symptomatic non-ischemic HF patients with LV ejection fraction (EF) greater than 40% and type 2 diabetes mellitus (T2DM) treated with administration of empagliflozin (10 mg/day) were enrolled. According to the myocardial extracellular volume fraction (ECV), a reliable marker of cardiac fibrosis quantified by cardiac magnetic resonance, the patients were divided into the early DMCMP group (n = 16, ECV ≤ 30%) and advanced DMCMP group (n = 19, ECV > 30%) and followed-up prospectively. Echocardiography was performed at baseline and after 12 months. LV systolic function assessed as LV global longitudinal strain (GLS) and diastolic function assessed as the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e’) were compared.Results: ECV was strongly correlated with T2DM duration (r2 = 0.65, p < 0.001). At baseline, both groups had similar backgrounds (LVGLS: 7.9 ± 2.4% vs. 6.7 ± 3.0%, p = 0.207, and E/e’: 13.2 ± 6.1 vs. 12.6 ± 3.8, p = 0.694). After 12 months, the early DMCMP group showed greater improvement in LVGLS (ΔLVGLS: 4.6 ± 1.5% vs. 1.6 ± 3.3%, p = 0.003) and E/e’ (ΔE/e’: -3.4 ± 5.5 vs. -0.1 ± 3.5, p = 0.043) than in the advanced DMCMP group.Conclusions: The positive effects of empagliflozin on LV dysfunction were more remarkable in DMCMP with mild cardiac fibrosis than with advanced fibrosis. Early intervention of SGLT2i for DMCMP is preferable.
Uncertainty Management Associated With Project Scheduling in Mine Construction: A Coal Mining Case Study
Authors: Renaud Matt , Kumral Mustafa
Published: December 2020

Due to the cyclical nature of commodity prices, the profitability of mining projects relies on proper timing. To ensure optimal profits, mines should be brought online at the time, which maximizes the potential value of the asset. In this paper, a coking coal mine construction case is used to demonstrate the effectiveness of scheduling large-scale construction projects with uncertain durations under price cyclicality. Project parameters are obtained stochastically via Monte Carlo sampling, allowing for the influence of uncertainty to be quantified. The critical path method and linear programming are employed to analyze the results and to optimize the construction process, ensuring the maximum value of the mining project. The parameters are repeatedly sampled to obtain distributions of possible project outcomes, allowing for risk and sensitivity quantification. The optimal schedule for construction was determined to be 247 weeks, with a most likely value of $813 million.
Reconstruction of Aesthetic Stomatognathic Function After a High-energy Maxillo-orofacial Fracture: a Case Report
Authors: Kataoka Toshiyuki , Amemiya Kei , Udagawa Gen , Akagi Yuichi , Kagawa Chie , Okamoto Toshihiro
Published: December 2020

Background: High-energy injury patients with head trauma often present with pan-jaw fractures involving loss of teeth and alveolar bone. They experience a significant decrease in their quality of life due to masticatory disorders, dysarthria, and poor aesthetics. In most cases, they are treated separately by a medical team and a prosthodontist. Moreover, removable dentures provide little satisfaction to the patients.Case presentation: A 29-year-old young woman suffered a high-energy trauma from a fall accident. Following surgery for a jaw fracture, she underwent occlusal reconstruction with osseointegrated implants. The same team performed maxillofacial surgery and prosthetic treatments, and the series of treatment plans included bone grafting and periodontal plastic surgery.Conclusions: The treatment proved successful after more than two years with no signs of peri-implantitis. The patient was highly satisfied with the results. Early intervention by an oral and maxillofacial surgeon in such patients is essential for a good prognosis. Surgeons and prosthodontists who belong to the same team could complete the treatment with fewer surgical procedures. Furthermore, implant treatment in a patient with oral and maxillofacial fractures might improve aesthetics and function.
Possible Case of Children Onset Systemic Lupus Erythematosus Triggered by Covid-19
Authors: Bettiol Clémence Odile , Ntagerwa Joseph , Greef Axel De , Tuerlinckx David , Boutsen Yves
Published: December 2020

This case report will present the case of an 11 years old child diagnosed with childhood-onset systemic lupus erythematosus (cSLE) during the coronavirus Covid-19 pandemic. Her initial symptoms were compatible with a Covid-19 infection but repeated PCR on naso-pharyngeal swabs were negative. Two serological assays were carried out but only one showed doubtful IgG results.Considering that viral infection could be responsible for autoimmune disease outbreaks and with increasing evidences of SARS Cov 2 actions on human inflammatory and immune systems; we discuss here a potential cSLE diagnosis triggered by Covid-19 infection.
The Relationship of Anti-Mullerian Hormone in Polycystic Ovary Syndrome Patients With Different Subgroups
Authors: Ran Yu , Li Cong , Yi Qiang , Qiao Hong , Yang Qing , Ye Yanli
Published: December 2020

Purpose To explore the value of anti-Mullerian hormone (AMH) in polycystic ovary syndrome (PCOS) patients for different phenotype and age, and identify the relationship between the hyperandrogenism (HA) and polycystic ovary morphology (PCOM) in Chinese cohort.Methods A total of 2262 women (1631 with PCOS and 631 health controls) were enrolled. The serum AMH and total testosterone (TT) were analyzed, compared the AMH level of each subgroup and evaluated the value of each phenotype and age group of PCOS.Results The level of AMH in PCOS(8.63±4.73ng/ml) was higher than that in health controls(5.57±3.31ng/ml) (P＜0.01).The level of AMH in PCOM subgroup(11.19±6.4ng/ml) was significantly higher than that in HA subgroup(8.58±4.74ng/ml) (P＜0.01), and both higher than that in health controls(P＜0.01). AMH changes highly in PCOS compared with the health control, but as the same value in subgroups of PCOS patients under 30-year-old.Conclusion AMH changed in different subgroups of PCOS, which was the possible reason why AMH was not a diagnostic indicator. However, AMH could differ the subgroup in clinical, AMH was strongly related with PCOM, not hyperandrogenism. AMH changed much as aged, but stable in PCOS patients under 30-year-old.
Diabetes, Even Newly Defined by HbA1c Testing, Is Associated With an Increased Risk of in-hospital Death in Adults With COVID-19
Authors: Liu Ye , Lu Ran , Wang Junhong , Cheng Qin , Zhang Ruitao , Zhang Shuisheng , Le Yunyi , Wang Haining , Xiao Wenhua , Gao Hongwei , Zeng Lin , Hong Tianpei
Published: December 2020

Background: Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19.Methods: This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was 6.5% (≥ 48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis. Results: Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs 5.9%, p <0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p <0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥ 1.0 mg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19.Conclusions: The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.
Movement of Dichlorvos in Farm Soils: Batch and Column Studies.
Authors: Bustos Nahuel , Grassi Diego , Cirelli Alicia Fernández , Iriel Analia
Published: December 2020

Soils are the principal environmental fate of pesticides in agricultural areas. Thus, the kinetics, extension, and strength of the adsorption process become critical. Dichlorvos (DDVP) is an organophosphorous pesticide that is used both in agriculture and livestock production. Sorption/desorption assays of DDVP in two agricultural soils (with different textural characteristics) from Pampa Plain (Argentina) were performed in both batch and column systems. From batch studies, kinetics and sorption/desorption equilibrium parameters were estimated. Our results showed that the maxima adsorption is reached after 30 h of time of contact and followed a pseudo-first-order rate. Adsorption/desorption data were well fitted to the Freundlich model obtaining high adsorption constants of 90 mg(1-1/n) mL(1/n) g-1 and 21 mg(1-1/n) mL(1/n) g-1 for the clay loam and sandy loam soil, respectively. The isotherms were non-linear in both cases and the desorption process was unfavourable. Also, positive hysteresis was present for the sandy loam soil. From column studies, breakthrough curves were used to evaluate the mobility of DDVP in the soils at 1, 10, and 50 mg L-1 of DDVP. Eluted profiles were asymmetrical as well they presented retardation effects that were in connection with the results in batch conditions. Non-equilibrium sorption was stated for the DDVP movement through columns. Thus, high mobility was observed for DDVP in both soils despite their textural differences.
Macular Thickness and Volume Assessed by Spectral-Domain Optical Coherence Tomography in Patients With Coronavirus Disease 2019: A Case-Control Study
Authors: Abrishami Mojtaba , Tohidinezhad Fariba , Emamverdian Zahra , Daneshvar Ramin , Saeedian Neda , Ansari-Astaneh Mohammad-Reza , Savastano Maria Cristina , Eslami Saeid
Published: December 2020

Purpose: To quantify the retinal thickness and volume using spectral-domain optical coherence tomography (SD-OCT) analysis in the macular region of patients with Coronavirus Disease 2019 (COVID-19).Methods: In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included. All included subjects had a reverse transcription-polymerase chain reaction (RT-PCR) - confirmed diagnosis of COVID-19. Macular SD-OCT was performed at least two weeks after recovery from systemic COVID-19. Inner, outer and full retinal thicknesses and volumes were measured in COVID-19 recovered patients versus age-matched normal controls.Results: Twenty-five patients (11 male) with a mean age of 36.4 ± 11 years and 60 healthy controls (31 males) with a mean age of 39.3 ± 7.7 years were enrolled in the study. There was no statistically significant difference in the retinal thickness or volume measures between the two groups. However, the thickness in the case group was minimally more than the controls. Conclusion: Retinal thickness in COVID-19 patients may be higher than healthy subjects. Comprehensive ocular examination with special focus on posterior segment manifestations should be considered in these patients.