bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Design of Phase II/III Clinical Trials for Testing Therapeutic Interventions in COVID-19 Patients
Authors: Rai Shesh , Qian Chen , Pan Jianmin , Seth Anand , Srivast Deo Kumar , Bhatnagar Aruni 
Published: June 2020

Abstract
Background Due to unknown features of the COVID-19 disease and complexity of the patient population, traditional clinical trial designs on treatments may not be optimal in such patients. We propose two independent clinical trials designs based on careful grouping of patient and outcome measures.Methods Using the World Health Organization ordinal scale on patient status, we classify treatable patients (Stages 3-7) into two risk groups. Patients in Stages 3, 4 and 5 are categorized as the intermediate-risk group while patients in Stages 6 and 7 are categorized as the high-risk group. To ensure that an intervention, if deemed efficacious, is promptly made available to vulnerable patients, we propose a group sequential design incorporating four factors stratification, two interim analyses, and a toxicity monitoring rule for the intermediate-risk group. The primary response variable (binary variable) is based on the proportion of patients discharged from hospital by the 15th day. The goal is to detect a meaningful improvement in this response rate. For the high-risk group, we propose a group sequential design incorporating three factors stratification, two interim analyses, and without toxicity monitoring. The primary response variable for this design is the 30 days mortality, and the goal is to detect a meaning reduction in mortality rate.Results Required sample size and toxicity boundaries are calculated for each scenario. Sample size requirements for the designs with interim analyses are marginally greater than the ones without. In addition, for both the intermediate-risk group and the high-risk group, conducting two interim analyses have almost identical required sample size compared with just one interim analysis. Conclusions We recommend using composite endpoints, with binary outcome for those in Stages 3, 4 and 5 with a power of 90% to detect an improvement of 20% in response rate, and 30 days mortality rate outcome for those in Stages 6 and 7 with a power of 90% to detect 15% (effect size) reduced mortality rate, in the trial design. For the intermediate-risk group, two interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.
The Investigation Of The Effect Of Hyperglycaemic Changes On Psychophysical Measurements Of Visual Function In Pseudophakic People Living With Diabetes Mellitus.
Authors: Majola Lindokuhle , Munsamy Alvin J 
Published: June 2020

Abstract
Background

Phakic people living with diabetes mellitus (PDM) have been known to complain of transient subjective visual disturbances, however it has yet to be shown if this can extended to pseuodphakia as well. The measurement of visual acuity (VA) and contrast sensitivity (CS) forms part for these visual disturbances and is regarded as psychophysical measurements of vision. The purpose of this study was to show the effect of increasing blood glucose level (BGL) on visual acuity and contrast sensitivity in pseudophakic PDM.
Methods

This was quasi-experimental, quantitative study using a pretest-posttest approach. The study was conducted at Gamalakhe community health centre and included a sample of 50 pseudophakic people living without diabetes mellitus (PWDM) and 50 pseudophakic-PDM. BGL as well as psychophysical measurements of visual function were measured pre-prandial and postprandial. VA was measured at distance (4 m) and near (40 cm) using LogMAR VA charts, CS was measured at 50 cm using Mars chart. Ethical permission was obtained before commencement of the study from Biomedical Research Ethics Committee (BREC) and KwaZulu-Natal Department of Health. The data collected was captured and subsequently analysed using the SPSS version 25. The Kruskal-Wallis Test and Wilcoxon Sign Ranked was used to compare changes within each group.
Results

Glycaemic changes observed had a mean increase of 2.06 ± 1.35 mmol/L and 1.08 ± 0.47 mmol/L in pseudophakia PDM and pseudophakic PWDM, respectively. A mean increase in CS of 0.01 ± 0.10 log units in PDM was found, however the independent T-Test showed this was insignificant between PDM and PWDM (p = 0.27). Mean increase in distance (0.01 ± 0.04 log units, p = 0.25) and near LogMAR VA (0.001 ± 0.01 log units, p = 0.32) for pseudophakic PDM was found, however the Mann-Whitney U-Test showed a statistically insignificant change p = 0.45 and p = 0.13 in distance and near VA respectively when compared to changes observed for pseudophakic PWDM.
Conclusions

Acute hyperglycaemic changes does not result in overall significant changes in visual acuity and contrast sensitivity in pseudophakic PDM for an increase in glycaemia of 2 mmol/L. However, the duration of DM may affect the CS in pseudophakic PDM without retinopathy who have had DM for greater than 10 years.
Smart@Home – Supporting safety and mobility of elderly and care dependent people in their own homes through the use of technical assistance systems and conventional mobility supporting tools: A cross-sectional survey
Authors: Jachan Deborah Elisabeth , Strube-Lahmann Sandra , Müller-Werdan Ursula , Lahmann Nils Axel 
Published: June 2020

Abstract
BACKGROUNDThe use of technical solutions and conventional mobility aids can support the independence of people into old age in their own homes. However, we found relatively few empirical investigations on the effects and costs of these systems.METHODSThe aim of the study was to investigate usability, user satisfaction and the correlation between costs and benefits of different built-in smart home solutions and conventional mobility supporting tools in the home of elderly, partially care-dependent tenants (> 65 years). A cross-sectional survey was conducted from February to March 2018 with tenants of a housing association in apartments equipped with smart home technology and conventional mobility supporting tools. The response rate in the intervention group was n = 37 persons (out of 46 tenants with installed smart home and conventional solutions) and in the control group n = 64 persons (out of 100 tenants without built-in smart home and conventional solutions). Data were collected by a written questionnaire regarding usability and satisfaction of the tenants with the built-in smart home solutions and conventional mobility supporting tools. In addition, both the intervention and the control group were asked general questions about communication, safety and how to deal with the need for long-term care in their own living environment.RESULTSResults showed that with regard to usability, satisfaction and price performance ratio of the installed smart home solutions, the installation of the corresponding solutions with an overall score of 1.41 was mostly positively evaluated by the tenants. Overall, users rated the installed smart home solutions better than the conventional mobility supporting tools (mobility aids, such as handholds and increased balcony floor level).CONCLUSIONSAnalysis of the price performance ratio showed that smart home solutions are generally more expensive than conventional tools, but also contribute significantly to an increased security of the tenants, and thus may enable longer living in a familiar environment. We recommend modularized offers consisting of various components of smart home solutions, since this significantly reduces installation costs and allows for an individual composition according to requirements. Moreover, smart home solutions should be considered to be listed as medical aids.
Bioinformatics Analysis of Prognostic value and prospective Pathway signal of miR-30a in Ovarian Cancer
Authors: Lu Weijia , Wu Yunyu , Lu CanXiong , Zhu Ting , Ren ZhongLu , Yu zhiwu 
Published: June 2020

Abstract
Objective: MicroRNAs (MiRNAs) is thought to play an critical role in the initiation and progress of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated.Methods:Three mRNA datasets of normal ovarian tissue and OC, GSE18520 ,GSE14407 and GSE36668, were downloaded from Gene Expression Omnibus(GEO) to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was conducted by STRING and Cytoscape, and the effect of HUB gene on the outcome of OC was analyzed.Results：A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.Conclusion：Our results indicate that miR-30a is of significance for the biological progress of OC.
Clinical characteristics and prognostic factors in elderly patients with COVID-19
Authors: Cheng Qin , Liao Yixuan , Lin Yujing , Tao Liyuan , Wang He , Li Mohan , Ge Qinggang , Li Yanming , Shen Ning 
Published: June 2020

Abstract
Background: The COVID-19 pandemic poses tremendous threats to the world. Elderly patients are among the high-risk population, and apt to experience worse outcomes.Methods: Elderly patients (age ≥60 years old) were enrolled from January 28 to February 29, 2020, in Tongji Hospital, one of designated COVID-19 medical centers in Wuhan, China.A retrospective study was performed to describe clinical characteristics, laboratory findings, chest imaging, treatment, and outcomes of elderly COVID-19 patients. COX regression was used to analyze predictors for 28-day mortality. Linear regression models were constructed to analyze factors associated with length of hospital stay.RESULT: A total of 186 elderly patients (aged 70.4 ± 7.1 years, 95 males (51.6%)) were enrolled, 120 patients (64.5%) were severe or critical type, and mortality rate was 16.1% (30/186). Of 156 survived patients, 150 were discharged. Fever (83.3%), cough (80.6%) and dyspnea (68.3%) were the most frequent symptoms. Common comorbidities included hypertension (48.9%) and diabetes (32.8%). Ground-glass opacities (97.3%) and peripheral distribution (59.1%) were the most predominant patterns on chest imaging. Patients in non-survival group had a higher smoking rate, more symptoms of dyspnea, lab results indicative of poorer health, and needed more medications or supportive treatment. Age (HR 1.128, 95% CI 1.066-1.194), lymphocyte count (HR 0.261, 95% CI 0.073-0.930), LDH (HR 1.003, 95% CI 1.002-1.005), PCT (HR 1.061, 95% CI 1.002-1.125), and qSOFA (HR 3.162, 95% CI 1.646-6.072) were predictors of death. CURB-65 plus LDH were strong predictors of death (AUROC=0.891). Among surviving patients, consolidation on CTs (β=8.611), elevated ferritin level (β=0.004) and neutrophil count (β=0.806) were associated with increased LOS.Conclusion: High incidence of comorbidities and mortality were observed in elderly patients. Decreased lymphocyte, older age, higher qSOFA score, PCT or LDH levels were associated with 28-day mortality, and CURB-65 plus LDH were strong predictive of death. Consolidation on CTs, elevated ferritin and neutrophil level correlated with increased LOS. Further prospective studies should be performed for potential treatments.
Asiatic Acid Attenuates Osteoarthritis by Regulating NF-κB Signaling Pathway in Chondrocytes
Authors: Yang Zhengmeng , Feng Lu , Zhang Xiaoting , Lin Weiping , Wang Bin , Lan Huiyao , Cui Liao , Huang Jianping , Lin Sien , Li Gang 
Published: June 2020

Abstract
Background: Natural small molecules have become more attractive as alternatives to non-steroidal anti-inflammatory drugs in osteoarthritis (OA) treatments. This study aims to investigate the effects of Asiatic acid (AA) on OA in chondrocytes and the surgery-induced OA animal model. Methods: Cytotoxicity of AA in primary rat articular chondrocytes was determined. Chondrocytes were pretreated with AA at the safe concentrations and subsequently treated with IL-1β. The production of inflammatory mediators including nitric oxide (NO), nitric oxide synthase (iNOS), as well as cyclooxygenase (COX)-2, and the expression of chondrogenic and hypertrophic markers including Sox 9, Aggrecan, Col 2a1, and matrix metalloproteinase-13 (MMP13) in the cells were measured. The effect of AA on nuclear factor-kappa B (NF-κB) signaling pathway was further determined by dual luciferase assay and western blot. The surgery-induced OA animals were treated with AA or saline for 6 weeks. The pathological changes in the affected joints were measured by micro-CT and histological analysis. Results: We found a broad safety spectrum of AA from 0 to 25 μM. A dose-dependent inhibitory effect of AA on NO production, as well as iNOS and COX-2 expression were found. Meanwhile, AA promoted chondrogenesis and inhibited hypertrophy in chondrocyte treated with IL-1β. In addition, AA inhibited NF-κB signaling pathway with a dose-dependent manner. Furthermore, results from animal study revealed that AA prevented articular cartilage damage as well as subchondral bone remodeling in the surgery-induced OA animal.
Rescue therapy with rifabutin regimen for refractory Helicobacter pylori infection with dual drug-resistant strain
Authors: Kuo Chia-Jung , Lin Cheng-Yu , Le Puo-Hsien , Chang Pi-Yueh , Lai Chih-Ho , Lin Wey-Ran , Chang Ming-Ling , Hsu Jun-Te , Cheng Hao-Tsai , Tseng Chi-Nan , Lin Chun-Jung , Su Ming-Yao , Hsieh Sen-Yung , Chiu Chengtang 
Published: June 2020

Abstract
Background: There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori. This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.Methods: After two or three H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistance was determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and received rifabutin based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test four weeks after treatment completion. Results: A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39). Adverse event was reported in 23.1% (9/39) of patients but mild and tolerable. In univariate analysis, no factor was identiﬁed as an independent predictor of eradication failure. Conclusions: Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.
Primary Drug-resistant Tuberculosis in the Elderly in Shandong,china,from 2004 - 2019.
Authors: An Qi-qi , Song Wan-mei , Liu Jin-yue , Tao Ning-ning , Liu Yao , Zhang Qian-yun , Xu Ting-ting , Li Shi-jin , Liu Si-Qi , Li Yi-Fan , Yu Chun-Bao , Li Huai-chen 
Published: June 2020

Abstract
Background: With an aging population, China is facing a huge buedern of elderly patients with drug resistant tuberculosisi (DR-TB), which has become an significant obscale for the global TB control targets. There is still few study on DR-TB among China so far.Thus, more researches on the epidemiological characteristics and trend of primary DR-TB among the elderly will be necessary. Methods: A retrospective study was conducted in Shandong, China from 2004-2019, 12661 primary TB and 4368 elderly (≥60 years of age) primary TB cases were involved. Clinical characteristics including age, sex, Cavity, Smoking, drinking, comorbidity and drug susceptibility data were included. Descriptive statistical analysis, Chi-square and linear regression were used for analyzing.Results: Among 4368 elderly patients with primary TB, the DR-TB and MDR-TB accounted for 17.19% and 2.29% respectively. During 2004 to 2019, the proportions of MDR-TB, PDR-TB, RFP-resistance increased by160.00%, 18.18%, 231.82%, and the rate of DR-TB among elderly patients with primary cavitary TB increased by 255%.Among the elderly with primary DR-TB, the proportion of male (from 85.19 to 89.06), cavity (from 7.41 to 46.88), RFP (from 3.70 to 21.88), SM (from 37.04 to 62.5) increased significantly(P<0.05) . And the proportion of female (from 14.81 to 10.94), non-cavity (from 92.59 to 32.81 ), INH (from 66.67 to 57.81 ) decreased significantly. (P<0.05) .Conclusion: Among the elderly, the proportions of MDR-TB, PDR-TB,RFP-resistance and cavitary DR-TB increased significantly. The pattern of DR-TB changed from female, non-cavity and INH-resistant groups to male, cavity and RFP, SM-resistant groups. In order to a better control on the elderly DR-TB in the future, we should pay more attention to, male, smoking, drinking, COPD and diabetes subgroups.
The correlation and mechanism between rumen microbiota disturbance and mastitis in dairy cows
Authors: Hu Xiaoyu , Guo Jian , Mu Ruiying , Jiang Peng , Zhao Caijun , Cao Yongguo , Zhang Naisheng , Fu Yunhe 
Published: June 2020

Abstract
Background: Mastitis, which is a highly prevalent disease in dairy cows and economically costly to the dairy industry worldwide, is commonly believed to be caused by local infection of the mammary gland. Recently, studies have suggested that the gut microbiota plays an important role in the development of cow mastitis, yet the mechanisms linking the gut microbiota to mastitis remain unclear. This study assessed the effects and mechanisms of rumen microbiota on mastitis based on the subacute rumen acidosis (SARA) model induced by feeding a high-concentration diet (HCD) to Holstein cows . Results: Lipopolysaccharides (LPS)-derived from the rumen translocated into the blood and then accumulated in the mammary glands by damaging the integrity of the blood-milk barrier and induced an inflammatory response in the mammary glands of SARA cows. Furthermore, elevation of the abundance of Stenotrophomonas was one of the endogenous factors to induce mastitis during cows suffering SARA. Finally, we found that rumen microbiota imbalance induced by SARA resulted in increased severity to mastitis by inhibiting the clearance of pathogens from the mammary glands in SARA cows. Conclusions: This study identifies rumen microbiota dysbiosis and LPS translocation from the rumen to the mammary gland as important factors to induce mastitis in cows. In addition, rumen microbiota imbalance increased mastitis susceptibility by inhibiting the ability of the mammary glands to clear out pathogens. Our studies provide a basis for novel therapeutic strategies that exploit the gut microbiota in cow mastitis.
Momordica Charantia Polysaccharides Modulate the Differentiation of Neural Stem Cells via SIRT1/Β-Catenin Axis in Cerebral Ischemia/Reperfusion
Authors: Hu Zhaoli , Li Fengying , Zhou Xiaoling , Zhang Feng , Huang Linyan , Gu Bing , Shen Jiangang , Qi Suhua 
Published: June 2020

Abstract
Background
Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their antioxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI).
Methods
We investigated MCPs’ function in differentiation of NSCs in vitro experiments. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of ischemia / reperfusion injury (IRI). We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation were also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1.
Results
MCPs had no effects on the differentiation of neural stem cells under physiological conditions, while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCPs-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs.
Conclusion
Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.
Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism
Authors: Chao Owen Y , Pathak Salil S , Zhang Hao , Dunaway Nathan , Li Jay-Shake , Mattern Claudia , Nikolaus Susanne , Huston Joseph P , Yang Yi-Mei 
Published: June 2020

Abstract
The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.