bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplement with whey protein hydrolysate in contrast to carbohydrate supports mitochondrial adaptations in trained runners
Authors: Hansen Mette , Oxfeldt Mikkel , Larsen Anne E. , Thomsen Lise S. , Torben Rokkedal-Lausch , Christensen Britt , Rittig Nikolaj , De Paoli Frank V. , Bangsbo Jens , Ørtenblad Niels , Madsen Klavs
Published: August 2020

Background: Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified.The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners.Methods: Twenty-four trained runners (VO2max 60.7±3.7 ml O2 kg-1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3g kg-1) before and protein-carbohydrate beverage (0.3g protein kg-1 and 1g carbohydrate kg-1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6K time trial (6K TT) and a VO2max test pre, midway (only 6K TT) and post intervention. Results: Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p<0.05), with several other mitochondrial proteins (Succinate dehydrogenase (SDHA), Cytochrome C oxidase (COX-IV), Voltage-dependent anion channel (VDAC), Heat shock protein 60 (HSP60), and Prohibitin (PHB1)) following a similar, but non-significant pattern (p=0.07-0.14). β-hydroxyacyl-CoA dehydrogenase (HAD) activity was significantly lower after training in the CHO group (p<0.01), but not in the PRO-CHO group (p=0.24). VO2max and 6K TT was significantly improved after training with no significant difference between groups.Conclusion: Intake of whey PRO hydrolysate before and whey PRO hydrolysate plus CHO after each exercise session during a six-week endurance training period may augment training effects on specific mitochondrial proteins compared to intake of iso-caloric CHO but does not alter VO2max or 6K TT performance.
Analysis of ACE2 Genetic Variants in 131 Italian SARS-CoV-2 Positive Patients
Authors: Novelli Antonio , Biancolella Michela , Borgiani Paola , Cocciadiferro Dario , Colona Vito Luigi , D’Apice Maria Rosaria , Rogliani Paola , Zaffina Salvatore , Leonardis Francesca , Campana Andrea , Raponi Massimiliano , Andreoni Massimo , Grelli Sandro , Novelli Giuseppe
Published: August 2020

Background Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East Respiratory Syndrome (MERS-CoV), the Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. Methods As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children’s Hospital, Rome. We used a large control group consisting of 1,000 individuals (500 males and 500 females).Results We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient.Conclusions Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.
Patterns of immune infiltration in gastric cancer and their clinical significance
Authors: Jin Yin , Tao Liping , Li Shengnan , Jin Shuqing , Cai Weiyang
Published: August 2020

Background: The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor- infiltrating immune cells (TIICs) activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer (GC) immune cell infiltration has not been identified so far.Reuslts: In this study, we comprehensively analyzed the TIICs abundance in GC for the first time by CIBERSORT. The fraction of TIICs subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes. Unsupervised clustering analysis revealed there existed three distinct TIICs subgroups with distinct survival patterns. We also focused on analyzing the prognostic influence of TIICs in TP53, TTP and PIK3CA molecular subtypes.Conclusions: Collectively, our data explored the differences of TIICs in GC, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.
Rice farming care as a novel method of green care farm in East Asian context: an implementation research
Authors: Ura Chiaki , Okamura Tsuyoshi , Yamazaki Sachiko , Shimmei Masaya , Torishima Keisuke , Eboshida Akira , Kawamuro Yu
Published: August 2020

BackgroundGreen care farms, which offer care for people with dementia in a farm setting, have been emerging in the Netherlands. The aim of this study was to 1) implement green care farms which use rice farming in Japan, 2) explore the positive experiences of rice farming care, and 3) compare the effect of rice farming care to that of usual care on well-being and cognitive ability.MethodsWe developed a new method of green care farm in Japan which uses rice farming, a farming that is practiced all over East Asia. The participants were 15 people with dementia (mean age = 75.6 ± 9.8 years) who participated in a one-hour rice farming care program once a week for 25 weeks. We also collected qualitative data on the positive experiences of study participants after the program. We also assessed the effect of the rice farming care strategy on well-being and cognitive function, compared to the usual care group which included 14 people with dementia (mean age = 79.9 ± 5.8 years) who were attending the near-by day-care.ResultsThe mean participation rate on the rice farming care group was 72.1%. After the intervention, participants reported experiencing enjoyment and connection during the program. It also changed the staff’s view on dementia. The green care farm group showed a significant improvement in well-being but no significant difference in cognitive function compared to the usual care group.ConclusionsGreen care farms which use rice farming are an evidence-based, empowerment-oriented, strengths-based, community-based dementia service, which also delivers meaningful experience for the people with dementia in East Asia.Trial registration: UMIN, UMIN000025020,　Registered 1 April 2017, https://upload.umin.ac.jp/cgi-open-bin/icdr/ctr_view_cb.cgi?recptno=R000028561&flwp_key=1007OLu4ZmnWjoKzgQyVv5PC
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

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

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

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

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

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

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

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

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.
RETRACTED: Developing a Model to Implement National Mental Health Policy Framework and Integration of Mental Health care into HIV Services at Primary Health Care Settings
Authors: Cele Winnie Baphumelele , Mhlongo Euphemia Mbali
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
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

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

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

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.
The Novel Role of LINC01235 in Metastasis of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition
Authors: Zhang Cheng , Liang Yu , Zhang Chun-Dong , Dai Dong-Qiu
Published: August 2020

BackgroundLncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). The present study aims to explore the role of LINC01235 in clinical significance, prognostic prediction and GC metastasis.MethodsWe identified differentially expressed lncRNAs using stomach adenocarcinoma RNA-Seq data from The Cancer Genome Atlas (TCGA). The expression of LINC01235 in GC cell lines and tissues were confirmed by qRT-PCR assay. The overall survival analysis and univariate/ multivariate Cox regression analysis were performed to explore the prognostic value of LINC01235. In vitro assays were utilized to assess the effect of LINC01235 in cell migration and invasion. Western blotting measured the expression of EMT-induced proteins.ResultsThis study determined that LINC01235 expression has a higher fold changes by analyzing TCGA RNA-Seq data. qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. In vitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins.ConclusionLINC01235 could promote GC cell metastasis via EMT and function as a prognostic biomarker.
Nuclear-capture of endosomes drives depletion of nuclear G-actin to promote SRF/MRTF gene expression and cancer cell invasiveness
Authors: Marco Sergi , Neilson Matthew , Moore Madeleine , Pérez-García Arantxa , Hall Holly , Mitchell Louise , Blanco Giovanny Rodriguez , Hedley Ann , Zanivan Sara , Norman Jim
Published: August 2020

Signals are relayed from receptor tyrosine kinases (RTKs) at the cell surface to effector systems in the cytoplasm and nucleus, and coordination of this process is important for the execution of migratory phenotypes, such as cell scattering and invasion. The endosomal system influences how RTK signalling is coded, but the ways in which it transmits these signals to the nucleus to influence gene expression are not yet clear. Here we show that an RTK, cMET promotes Rab17-dependent endocytosis of EphA2, another RTK, followed by centripetal transport of EphA2-positive endosomes. EphA2 then mediates physical capture of endosomes on the outer surface of the nucleus; a process involving interaction between the nuclear import machinery and a nuclear localisation sequence in EphA2’s cytodomain. Nuclear capture of EphA2 promotes RhoG-dependent phosphorylation of the actin-binding protein, cofilin to oppose nuclear import of G-actin. The resulting depletion of nuclear G-actin drives transcription of Myocardin-related transcription factor (MRTF)/serum-response factor (SRF)-target genes to implement cell scattering and the invasive behaviour of cancer cells.
Methods to Evaluate the Twin Formation Energy: Comparative Studies of the Atomic Simulations and in-situ Tem Tensile Tests
Authors: Kim Hong-Kyu , Kim Sung-Hoon , Ahn Jae-Pyoung
Published: August 2020

Deformation twinning (DT), one of the major deformation modes in a crystalline material, has typically been analyzed using generalized planar fault energy (GPFE) curves. Despite the significance of these curves in understanding the twin nucleation and its effect on the mechanical properties of crystals, their validity has never been evaluated experimentally. In this comparative study based on the first-principles calculation, molecular dynamics (MD) simulation, and quantitative in-situ tensile testing of Al nanowires (NWs) inside a transmission electron microscopy (TEM) system, we present both a theoretical and an experimental approach that enable the measurement of a part of the twin formation energy of the perfect Al crystal. The proposed experimental method is also regarded as an indirect but quantitative means for validating the GPFE theory.
A Comprehensive Follow-Up Study Identifying Diagnostic Evidences for Secondary Finding
Authors: li shu , haoyu li , neng xiao , yixiang lin , wenxian yu , yingjing li , hui xi , zhengjun jia , fuli yu , hua wang , xiao mao
Published: August 2020

Background：There was a lacking of clinical diagnostic evidence in follow-up studies for reporting of secondary variants in 59 genes in American College of Medical Genetics and Genomics recommendations for reporting secondary findings and various strategies were applied to interpret the secondary variants. Results: Out of 1330 participants performed whole-exome sequencing, we identified 15 families with convincing clinical evidence. After Sanger validation and a comprehensive clinical follow-up, 10 families with both convincing clinical evidence and convincing genetic evidence of hereditary variants were found. Detailed clinical presentations and related clinical evidence were collected. Conclusions: Our research is a comprehensive follow-up study to identify secondary variants with convincing genetic and clinical evidence and it could help improve the strategy of screening actionable secondary variants and contribute to translation of genetic findings into medical practice.
Open Versus Arthroscopic Release for Lateral Patellar Compression Syndrome: A Randomized Control Trial
Authors: Hamawandi Sherwan , Amin Hazhar , Al-Humairi Ameer Kadhim
Published: August 2020

Background: Lateral patellar compression syndrome is one of the causes of anterior knee pain in young adults and resulted from tight lateral patellar retinaculum, which can be treated by surgical release of tight retinaculum after failure of conservative measures. Surgical release can be done by open or arthroscopic procedures. There was no randomized control trial to compare between these two procedures in considering of functional outcome and complications. The aim of our study is to compare between open and arthroscopic release of lateral patellar compression syndrome in relation of functional outcome, time of surgical procedure, length of hospital stays, intraoperative and postoperative complications as bleeding, infection, recurrence and patellar instability with 2 years of follow up. Methods: 80 patients, age (21-49 years), were divided randomly into 2 groups (A and B). Group A (40 patients) were treated with open release after diagnostic arthroscopy. Group B (40 patients) were treated by arthroscopic release. All these patients are diagnosed as lateral patellar compression syndrome depending on clinical features, MRI and diagnostic arthroscopy and they had failure of conservative measures of quadriceps strengthening and analgesics for 6 months. All patients were assessed by Lysholm knee scoring scale before surgery and at periods of 2 weeks, 6 weeks, 6 months, 12 months and 24 months after surgery.Results: There is significant difference in functional outcome, measured by Lysholm knee scoring scale, between preoperative and postoperative assessment periods in both groups (P<0.001). There is significantly better functional outcome at 2 years of follow up with the arthroscopic release (P=0.018). There is no recurrence in both groups, but there were 4 patients develop medial patellar instability in the group that was treated by open release. There are 2 patients develop hemarthrosis in arthroscopic group and one patient develop superficial wound infection in the group of open release. There is no significant difference in the postoperative complications between two groups.Conclusion: Both open and arthroscopic lateral release for patients with lateral patellar compression syndrome (without instability, limb malalignment or dysplasia) are effective surgical procedures but arthroscopic release can achieve better functional outcome than open release with less risk of development of post-operative patellar instability.Trial registration: NCT, NCT04130412. Registered 15 October 2019 -Retrospectively registered, https://www.clinicaltrials.gov/NCT04130412
Association of Diabetes and Outcomes in Patients with COVID-19: A Propensity Score Matched Analyses from a French Retrospective Cohort
Authors: Sutter Willy , Duceau Baptiste , Carlier Aurélie , Trimaille Antonin , Pommier Thibaut , Weizman Oriane , Cellier Joffrey , Geneste Laura , Panagides Vassili , Marsou Wassima , Deney Antoine , Attou Sabir , Delmotte Thomas , Ribeyrolles Sophie , Chemaly Pascale , Karsenty Clément , Giordano Gauthier , Gautier Alexandre , Chaumont Corentin , Guilleminot Pierre , Sagnard Audrey , Pastier Julie , Vignac maxime , Mika delphine , Fauvel Charles , Pezel Théo , Cohen Ariel , Bonnet Guillaume , Roussel Ronan , POTIER Louis
Published: August 2020

Background: To compare the clinical outcomes between patients with and without diabetes admitted to hospital with COVID-19.Methods: Retrospective multicentre cohort study from 24 academic tertiary medical centres in France including 2851 patients (675 with diabetes) hospitalised for COVID-19 between February 26 and April 20, 2020. A propensity score matching method (1:1 matching including patient characteristics, medical history, vital signs, and laboratory results) was used to compare patients with and without diabetes (n=603 in each group). The primary outcome was admission to intensive care unit (ICU) or in-hospital death. Results: Patients with diabetes were older (71 ± 13 vs. 65 ± 18 years; p<0.001), were less often female (38% vs. 44%; p<0.001) and more likely to have comorbidities: hypertension (79% vs 42%; p<0.001), coronary heart disease (23% vs 9%; p<0.001), stroke (13% vs 8%; p<0.001), heart failure (17% vs 9%; p<0.001), chronic kidney disease (26% vs 10%; p<0.001), and chronic obstructive pulmonary disease (7% vs 5%; p<0.05). The primary outcome occurred in 584 (36.4%) patients with diabetes compared to 246 (26.8%) in those without diabetes (p<0.001). After propensity score matching, the risk of primary outcome was similar in patients with and without diabetes (hazard ratio [HR] 1.16, 95%CI 0.95-1.41, p=0.14) and was 1.29 (95%CI 0.97 – 1.69) for in-hospital mortality, 1.26 (95%CI 0.93 – 1.72) for mortality without transfer in ICU, and 1.14 (95%CI 0.88 – 1.47) for transfer to ICU.Conclusions: In this retrospective cohort of patients hospitalised for COVID-19, diabetes was not significantly associated with a higher risk of COVID-19 severe outcomes after propensity score matching.Trial registration NCT04344327
LacminCC: Lightweight Anonymous Communication Model In Cloud Computing
Authors: Li Fengyin , Wang Yanli , Ju Hongwei , Yu Xinying , Wang Zhaojie , Zhou Huiyu
Published: August 2020

With increasing application of cloud computing and big data technologies, a large amount of personal information is stored on the Internet, which raises the issue of privacy leakage. In order to protect people's data privacy, this paper firstly presents a new anonymous Identify-Based Encryption (IBE) scheme and shows the proof of its security under the Bilinear Diffie-Hellman Security Assumption. Then, by introducing the anonymous IBE scheme into an anonymous communication model, this paper introduces a new lightweight anonymous communication model for cloud computing, which guarantees the anonymity of system users and the security of messages during the communication in small groups. Our analysis shows that, the proposed communication model cannot only reduce memory consumption and improve message transmission efficiency, but also effectively resist traffic-analysis attacks, node eavesdropping, and finally achieve secure anonymous communication in cloud computing.
Dynamic versus Static Ultra-widefield Fluorescein Angiography in Eyes with Diabetic Retinopathy: A Pilot Prospective Cross-sectional Study
Authors: Shen Hangqi , Wang Jing , Niu Tian , Chen Jili , Xu Xun
Published: August 2020

Background: Dynamic angiography can present additional information. However, evidence-based support in clinical application of dynamic modalities remain insufficient. The purpose of this study is to analyze differences in ultra-widefield fluorescein angiography (UWFA) findings between time-lapse dynamic and static imaging in eyes with diabetic retinopathy (DR).Methods: Twenty-eight eyes of 28 DR patients undergoing UWFA were included in the cross-sectional study. A series of UWFA images from each patient were converted into a time-lapse video in a Moving Picture Experts Group 4 movie format as a dynamic image. A single clear arteriovenous phase image was chosen as a static UWFA image. Non-perfusion index (NPI) and its correlation with intraretinal microvascular abnormality and neovascularization in different retinal zones were compared between dynamic and static UWFA imaging in severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).Results: NPI appeared to increase from the center to the far-periphery in both groups. Dynamic NPI appeared to be lower in the total retinal area (0.25 vs 0.28, p=0.005), far-periphery (0.30 vs 0.34, adjusted p=0.040) and superior quadrant (0.27 vs 0.34, adjusted p=0.045) in contrast to static NPI. Far-peripheral NPI was associated with intraretinal microvascular abnormality in posterior area in both groups.Conclusion: Time-lapse dynamic UWFA imaging is a useful method in the differential diagnosis of hypofluorescence in the most peripheral region, which may provide a reliable measurement of NPI and improve the diagnostic accuracy of DR.
Sarcopenic Characteristics of Active Older Adults: A Cross-sectional Exploration.
Authors: Huschtscha Zoya , Parr Alexander , Porter Judi , Costa Ricardo da
Published: August 2020

Background: Ageing is associated with a decline in skeletal muscle mass and function (strength and power), known as sarcopenia. Inadequate dietary protein and inactivity have been shown to accelerate sarcopenia outcomes, occurring at different rates in males and females. Regardless, active older adults who often exceed the exercise guidelines still show signs of sarcopenia. This study aimed to explore the link between age, physical activity, protein intake, and biological sex with skeletal muscle mass, strength, power, and physical capacity/performance in active older adults. Methods: Fifty-four active older adults were grouped according to age (middle aged: 50-59 years, and older age: ≥60 years), exercise volume (low: <150min/week, moderate: >150-299min/week, and high: >300min/week), protein intake (low: <0.8g/kg body mass (BM), moderate: ≥0.8-1.19g/kgBM, and high: ≥1.2g/kgBM), and biological sex (males and females). Skeletal muscle and fat mass (dual x-ray absorptiometry), strength (1-repetition maximum using leg press, chest press, lateral pull down, and hand grip), power (counter movement jump), and general fitness (cardiorespiratory capacity and gait speed) were assessed. Data were grouped based on variables, and a one-way ANOVA (or non-parametric equivalent) was applied to assess group differences. Results: The middle-aged group had a 13%, 17%, and 12% higher leg press, chest press, and lateral pull down, respectively, compared to the older aged group (P<0.05). Participants that reported moderate and high training volumes had lower body fat mass compared to those that reported lower training volumes (26.1%, 25.1%, and 35.6%, respectively; P<0.001). Similarly, higher leg press (22% and 27%) and chest press (22% and 23%) was observed with moderate and high training volumes compared with lower. Higher protein intakes were associated with significantly less body fat mass (P=0.019), higher leg strength (P=0.038) and relative power (W/kg) (P=0.048) compared to the moderate and low protein intake groups. Significant differences based on biological sex were observed for all outcomes expect for gait speed (P=0.611) and cardiorespiratory fitness (P=0.147).Conclusion: Contributions of age, physical activity, daily protein intake, and biological sex can explain the individual variation in outcomes related to changes in body composition, strength, power, and/or cardiorespiratory fitness in a cohort of active older adults.