bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperpolarized Magnetic Resonance Shows that the Anti-Ischemic Drug, Meldonium, Leads to Increased Flux Through Pyruvate Dehydrogenase In Vivo Resulting in Improved Post-Ischemic Function in the Diabetic Heart.
Authors: Savic Dragana , Ball Vicky , Holzner Lorenz , Hauton David , Timm Kerstin , Curtis M. Kate , Heather Lisa C. , Tyler Damian J. 
Published: August 2020

Abstract
Background: The diabetic heart has a decreased ability to metabolize glucose. The anti-ischemic drug, Meldonium, may provide a route to counteract this by reducing L-carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with Meldonium on cardiac metabolism and function in control and diabetic rats. Methods: 36 male Wistar rats were injected with either placebo or streptozotocin (55mg/kg) to induce a model of type-1 diabetes. Daily treatment with either saline or Meldonium (100mg/kg/day) was undertaken for three weeks. In vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low-flow ischemia/reperfusion to assess the impact of Meldonium on post-ischemic recovery.Results: Meldonium had no significant effect on blood glucose levels or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that Meldonium treatment elevated pyruvate dehydrogenase flux by 3.1-fold and 1.2-fold in diabetic and control animals respectively, indicating an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that Meldonium reduced acetylcarnitine by 2.1-fold in both diabetic and control animals. The increase in in vivo glucose oxidation was accompanied by an improvement in ex vivo post-ischemic function, where Meldonium elevated rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals respectively. Conclusion: Meldonium improves in vivo glucose utilization in the diabetic heart, contributing to improved cardiac recovery post-ischemia.
Metformin Has No Impact on Nitric Oxide Production in Patients With Pre-diabetes
Authors: Sutkowska Edyta , Fortuna Paulina , Kałuża Bernadetta , Sutkowska Karolina , Wiśniewski Jerzy , Gamian Andrzej 
Published: August 2020

Abstract
Background: The effect of metformin on vascular system is still not fully understood and the studies performed on animals have suggested possible impact on the nitric oxide (NO) bioavailability. Aim: The evaluation of different doses of metformin impact on NO production in people with pre-diabetes.Methods: The metformin-naïve patients from one Diabetic Center with new-diagnosed pre-diabetes, without cardio-vascular diseases, were randomised (regarding to the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 x 500 mg, group B 3 x 1000mg) for 15 weeks. The wide panel of L-arginine/NO pathway metabolites concentrations was assessed using the LC-MS/MS. Results: Between October 2017 and December 2018, 36 individuals were initially randomised to intervention groups, but 25 accomplished the study: 14 patients in group A, 11 in group B; also 11 healthy volunteers were recruited. There was no difference between participants with pre-diabetes and healthy volunteers as regards the baseline characteristics except for fasting glucose and fatty liver. The decrease of L-citrulline concentration only was reported for treatment groups during the intervention period, with no change for the other NO-production related substances.Conclusions: It was the first study on the in vivo release of NO in humans at different metformin doses, in patients with pre-diabetes. Metformin has no impact on NO production irrespective of the dose. The citrulline concentration change can indicate the drug impact on altered enterocytes’ condition. The small number of patients is a limitation of the study.Trial registration: ClinicalTrials; number: NCT03398356; retrospectively registered- date of registration:01 July 2018; https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007ODV&selectaction=Edit&uid=U0003WJC&ts=4&cx=1y9eeb
Radiological and clinical effect of balloon kyphoplasty for the management of rheumatoid arthritis patients with osteoporotic vertebral compression fracture
Authors: Guo Ji , Zhai Weifeng , Wei Licheng , Zhang Jianpo , Jin Lang , Yan Hao , Huang Zheng , Jia Yongwei 
Published: August 2020

Abstract
Objective: This study was conducted to investigate the outcome of percutaneous balloon kyphoplasty (KP) for the treatment of osteoporotic vertebral compression fracture(OVCF) in patients with rheumatoid arthritis (RA) and analyze the influence of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), injected cement volume and duration of taking glucocorticoid on the outcome of KP procedure. Methods: A total of 39 RA patients (63 vertebral bodies) and 38 patients (50 vertebral bodies) without RA received KP management for OVCF. Changes in vertebral compression rate, local kyphotic angle, conditions of bone cement leakage, visual analogue scale (VAS) and Oswestry disability index (ODI) scores were evaluated for radiological and clinical outcomes of KP procedure. In addition, 39 OVCF patients with RA were divided into different groups according to the value of ESR, CRP, injected cement volume and duration of taking glucocorticoid to evaluate their influence on the outcomes of KP procedure.Results: The KP procedure significantly improved the compression rate, local kyphotic angle, VAS and ODI scores in both RA group and control group. The compression rate increased 11.56±3.8% in RA group which is significantly larger than the control group(p<0.05). The change of local kyphotic angle in RA group was 3.77±1.9, which is also larger than that in control group(p<0.05). Whereas, the changes of VAS and ODI scores were not significantly different between the two groups. Besides, radiological and clinical outcomes were not significantly different among the groups of different ESR, CRP, injected cement volume and duration of taking glucocorticoid no matter before or 1 year after the KP procedure, but 44% RA patients who take glucocorticoid for over 10 years had cement leakage after the KP procedure which is significantly higher than the group of RA patients with less than 10 years glucocorticoid use(p<0.05). In addition, 7 intradiscal cement leakage occurred in patients take glucocorticoid over 10 years where as no intradiscal leakage showed up in its control group(p<0.01).Conclusion: KP procedure was effective for OVCF patients with or without RA, for restoring vertebral body height, reducing local kyphotic angle, relieving pain and recovering spinal function. Compared to the control group, RA patients received more improvement in compression rate and local kyphotic angle after the operation. Intradiscal leakage occurred more in patients who take glucocorticoid for over 10 years.
Diabetes Patients of COVID-19 Infection Treated with Convalescent Plasma Transfusion in Wuhan, China
Authors: Dai Wei , Wu Jian , Li Tianfu , Shen Jiawei , Pang Rongrong , He Bangshun , Luo Tao , Guo Yanju , Yang Yang , Zhao Jun , Zhang Mingchao , Li Na , Han Ying , Wu Qiuyue , Li Weiwei , Xia Xinyi 
Published: August 2020

Abstract
Background: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 had spread all over the world, causing public health emergency. Although the diagnosis for COVID-19 such as nucleic acid test and antibody detection have been well defined, there is still a big gap of knowledge regarding for COVID-19 patients receiving convalescent plasma transfusion (CPT) therapy, especially patients with comorbidity of diabetes. Method: In this study, out of 3059 COVID-19 patients admitted in Wuhan Huoshenshan Hospital of China, we described the characteristics of 39 diabetes patients receiving the transfusion of ABO-compatible convalescent plasma, and compared the baseline information and clinical outcome with that of 328 diabetes patients receiving traditional treatment. Results: It was found that the intervention of CPT therapy was effective and beneficial for COVID-19 patients, including severe or critical patients with comorbidity of diabetes, without obvious adverse effects observing during the treatments. The CPT therapy significantly improved the clinical outcome of diabetes patients with COVID-19 infection, especially the duration based on six categories compared to the patients with traditional therapy. Conclusions: This study not only provided a better understanding of COVID-19 in diabetes people receiving CPT, but also highlighted the CPT therapy was helpful for COVID-19 patients with comorbidity of diabetes.
Prognostic Role of Porphyromonas Gingivalis in Oral Cavity Squamous Cell Carcinoma Patients
Authors: Chen Qingli , Shao Zhe , Liu Ke , Zhou Xiaocheng , Wang Lin , Jiang Erhui , Luo Tingting , Shang Zhengjun 
Published: August 2020

Abstract
Background: Oral microbial species play direct and/or indirect role in carcinogenesis of oral cavity squamous cell carcinoma (OSCC). Porphyromonas gingivalis (Pg) has been identified a correlation with OSCC. Fimbriae play a vital role for its attribution of initial attachment and adhesion of Pg. Six genotypes (types I-V, Ib) of fimA were identified based on sequence variations and the genotype was suggested a relationship to pathogenicity of Pg.Objective: To investigate the abundance of Pg in OSCC as well as the frequency of Pg fimA genotypes in OSCC patients.Methods: Ninety-five OSCC patients and thirty-nine gender- and age-matched non-OSCC subjects were investigated abundance of Pg in saliva. Presence of Pg was compared in OSCC tissue and para-cancerous tissue from patient as well. Clinical data were extracted and patients followed up for a mean period of 13 months. Presence of Pg and fimA genotypes were investigated in OSCC tissue and in saliva, then PCR products were sequencing and compared.Results: OSCC patients showed high abundance of Pg in saliva (Chi-square=14.531, P=0.001). OSCC tissue showed strong in situ expression of Pg by in situ hybridization compared with normal tissue adjacent to OSCC. Patients with overabundance of Pg in saliva are associated with systemic disease (Chi-square=10.328, P=0.029), longer disease-free time (Z=-2.988, P=0.003), and lower recurrence rate (Chi-square=5.670, P=0.017). The abundance of Pg was an independent favorable prognostic factor (HR: 0.124, 95%CI: 0.016 to 0.941). There was dominant distribution of Pg with genotype I+Ib (21.1%), II (31.6%) and IV (21.1%) in OSCC patients. The fimA genotypes detected in saliva were in accordance with those in OSCC tissue, and there was significantly correlation in amplified Pg fragments similarity between in saliva and in OSCC tissue. Conclusions: This study indicated that Pg might involve in the pathogenesis of OSCC, and Pg might consider as a potential prognostic indicator in OSCC. There was a dominant distribution of Pg with genotypes I, Ib, II and IV in OSCC patients. The presence of Pg in tumor might be saliva in provenance.
An efficient computational Method for Predicting Drug-Target Interactions using Weighted Extreme Learning Machine and Speed Up Robot Features
Authors: An Ji Yong , Meng Fan-Rong , Yan Zi-Ji 
Published: August 2020

Abstract
Background: Prediction of novel Drug–Target interactions (DTIs) plays an important role in discovering new drug candidates and finding new proteins to target. In consideration of the time-consuming and expensive of experimental methods. Therefore, it is a challenging task that how to develop efficient computational approaches for the accurate predicting potential associations between drug and target.Results: In the paper, we proposed a novel computational method called WELM-SURF based on drug fingerprints and protein evolutionary information for identifying DTIs. More specifically, for exploiting protein sequence feature, Position Specific Scoring Matrix (PSSM) is applied to capturing protein evolutionary information and Speed up robot features (SURF) is employed to extract sequence key feature from PSSM. For drug fingerprints, the chemical structure of molecular substructure fingerprints was used to represent drug as feature vector. Take account of the advantage that the Weighted Extreme Learning Machine (WELM) has short training time, good generalization ability, and most importantly ability to efficiently execute classification by optimizing the loss function of weight matrix. Therefore, the WELM classifier is used to carry out classification based on extracted features for predicting DTIs. The performance of the WELM-SURF model was evaluated by experimental validations on enzyme, ion channel, GPCRs and nuclear receptor datasets by using fivefold cross-validation test. The WELM-SURF obtained average accuracies of 93.54%, 90.58%, 85.43% and 77.45% on enzyme, ion channels, GPCRs and nuclear receptor dataset respectively. We also compared our performance with the Extreme Learning Machine (ELM), the state-of-the-art Support Vector Machine (SVM) on enzyme and ion channels dataset and other exiting methods on four datasets. By comparing with experimental results, the performance of WELM-SURF is significantly better than that of ELM, SVM and other previous methods in the domain.Conclusion: The results demonstrated that the proposed WELM-SURF model is competent for predicting DTIs with high accuracy and robustness. It is anticipated that the WELM-SURF method is a useful computational tool to facilitate widely bioinformatics studies related to DTIs prediction.
Impact of a Transition Education Program on the Quality of Life in Pediatric Patients with Congenital Heart Disease: Study Design for a Randomised Controlled Trial
Authors: werner Oscar , Bredy Charlene , LAVASTRE Kathleen , Guillaumont Sophie , VILLEON Gregoire De LA , Vincenti Marie , gerl Cristelle , DULAC Yves , Souletie Nathalie , ACAR Philippe , Pages Laurence , PICOT Marie christine a , Bourrel Gerard , ENGBERINK Agnes OUDE , Millon Elodie , Hamouda ABASSI , Amedro Pascal 
Published: August 2020

Abstract
Background: Recent advances in the field of congenital heart disease (CHD) led to an improved prognosis of the patients and in consequence the growth of a new population: the grown up with congenital heart disease. Until recently, more than 50% of these patients were lost to follow up because of the lack of specialized structures. The critical moment is the transition between paediatric and adult unit. Therapeutic education is crucial to solve this issue by helping patient to become independent and responsible. The TRANSITION randomized trial aims to assess the impact of a transition education program on the quality of life (QoL) of adolescents and young adults with CHD. Methods: multicentre, randomised, controlled, parallel arm study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (Education program vs. no intervention). The primary outcome is the change in self-reported QoL between baseline and 12-month follow-up. A total of 100 patients in each group is required to observe a significant increase of the overall QoL score of 7±13.5 points (on 100) with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VO2max,VE/VCO2 slope), level of knowledge, physical and psychological status.Discussion: As the current research is opening on patient related outcomes, and as the level of proof in therapeutic education still low, we sought to assess the efficacy of a therapeutic education program on the QoL of CHD patients with a randomized trial.Trial registration: This study was approved by the National Ethics Committee (South-Mediterranean IV 2016-A01681-50) and was registered on Clinicaltrials.gov (NCT03005626) on 29th December 2016
Anticonvulsant Use and Bone Health in a Population-based Study of Men and Women: Cross-sectional Data from the Geelong Osteoporosis Study.
Authors: Chandrasekaran Vinoomika , Pasco Julie A , Stuart Amanda L , Brennan-Olsen Sharon L , Berk Michael , Hodge Jason M , Samarasinghe Rasika M , Williams Lana J 
Published: August 2020

Abstract
Background: Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based sample of men and women.Methods: Data from 1996 people, 926 men (age:24-73y) and 1070 women (21-94y) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm2) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. Results: Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index (28.5 kg/m2) was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. No significant association was observed between anticonvulsant use in women and spinal BMD, SOS, BUA or SI but BMD tended to be 5.8% lower at the hip compared to non-users. Conclusion: Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.
Supervised Machine Learning Models and Protein-protein Interaction Network Analysis of Gene Expression Profiles Induced by Omega-3 Polyunsaturated Fatty Acids
Authors: Shityakov Sergey , Chang Jane Pei-Chen , Sun Ching-Fang , Guu David Ta-Wei , Dandekar Thomas , Su Kuan-Pin 
Published: August 2020

Abstract
BackgroundOmega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acids have beneficial effects on human health but their effect on gene expression in elderly individuals (age ≥ 65) is largely unknown. To examine this, the gene expression profiles were analyzed in the healthy subjects (n = 96) at baseline and after 26 weeks of supplementation with EPA+DHA to determine up-regulated and down-regulated differentially expressed genes (DEGs) triggered by PUFAs. The protein-protein interaction networks were constructed by mapping these DEGs to a human interactome and linking them to the specific pathways.ResultsThe results revealed that up-regulated DEGs were associated with neurotrophin/MAPK signaling, whereas the down-regulated DEGs were linked to the cancer, acute myeloid leukemia, and long-term depression pathways. Additionally, machine learning (ML) approaches were able to cluster the EPA/DHA-treated and control groups by the logistic regression algorithm performing the best. ConclusionOverall, this study highlights the pivotal changes in DEGs induced by PUFAs and provides the rationale for the implementation of ML algorithms as predictive models for this type of biomedical data.
Protein kinase A controls the hexosamine pathway by tuning the feedback inhibition of GFAT-1
Authors: Ruegenberg Sabine , Mayr Felix , Miethe Stephan , Atanassov Ilian , Baumann Ulrich , Denzel Martin 
Published: August 2020

Abstract
The hexosamine pathway (HP) is a key anabolic pathway whose product uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) is an essential precursor for all glycosylation processes in mammals. It modulates the ER stress response and HP activation extends lifespan in Caenorhabditis elegans. The highly conserved glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting HP enzyme. GFAT-1 activity is modulated by UDP-GlcNAc feedback inhibition and through phosphorylation by protein kinase A (PKA). Molecular consequences of GFAT-1 phosphorylation, however, remain poorly understood. Here, we identify the GFAT-1 R203H substitution that elevates UDP-GlcNAc levels in C. elegans. In human GFAT-1, the R203H substitution interfered with both UDP-GlcNAc inhibition and with PKA-mediated Ser205 phosphorylation. Our data indicate that phosphorylation affects the relative positioning of the two GFAT-1 domains to control its activity. Of note, Ser205 phosphorylation had two discernible effects: It lowered baseline GFAT-1 activity and abolished UDP-GlcNAc feedback inhibition. Thus, PKA controls the HP by uncoupling the metabolic feedback loop of GFAT-1.
The Prognostic Value of Seminal Anti-Sperm Antibodies Screening in Men Prepared for ICSI: A Call to Change the Current Antibody-directed Viewpoint of Sperm Autoimmunity Testing.
Authors: El-Sherbiny Ahmed F. , Ali Tamer A. , Hassan Eman A. , El-Sayed Mohamed E. , Elshemy Heba A. 
Published: August 2020

Abstract
Objective: To prospectively evaluate the prognostic value of seminal anti-sperm antibodies screening in couples prepared for intracytoplasmic sperm injection.Methods: A prospective comparative study was conducted, including 184 non-azoospermic infertile men scheduled for ICSI. For each patient, detection of anti-sperm antibodies in seminal plasma using ELISA technique was done and its relation to standard semen parameters and ICSI outcomes, including fertilization, embryo development, and pregnancy rates, were analyzed.Results: Sperm count, motility, and morphology were negatively affected by existence of seminal ASA (p=0.012, 0.006, and 0.011, respectively). However, no statistically significant difference was detected between patients with positive and negative seminal ASA regarding the median values of fertilization (56.3% Vs. 66.7%, p =0.091), percentage of couples with grade A embryo development (91.4% vs. 89.9%, p= 0.520), and pregnancy rates (31.4% vs. 32.2%, p =0.98) after ICSI.Conclusion: ICSI seems able to overcome the problem of ASA in semen. The routine screening of ASA in men prepared for ICSI has no additional prognostic value and cannot be recom­mended for the time being, until more specific antigen-concerned testing can be developed.