bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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

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

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.
Air versus water chilling of chicken: a pilot study of quality, shelf-life, microbial ecology, and economics
Authors: Belk Aeriel D , Duarte Toni L , Quinn Casey , Coil David A , Belk Keith E , Eisen Jonathan A , Quinn Jason C , Martin Jennifer N , Yang Xiang , Metcalf Jessica L
Published: June 2020

Background. The United States’ large-scale poultry meat industry is energy and water intensive, and opportunities may exist to improve sustainability during the broiler chilling process. After harvest, the internal temperature of the chicken is rapidly cooled to inhibit bacterial growth that would otherwise compromise the safety of the product. This step is accomplished most commonly by water immersion chilling in the United States, while air chilling methods dominate other global markets. A comprehensive understanding of the differences between these chilling methods is lacking. Therefore, we assessed the meat quality, shelf-life, microbial ecology, and technoeconomic impacts of chilling methods on chicken broilers in a university meat laboratory setting. Results. We discovered that air-chilling (AC) methods resulted in superior chicken odor and shelf-life, especially prior to 14 days of dark storage. Moreover, we demonstrated that AC resulted in a more diverse microbiome that we hypothesize may delay the dominance of the spoilage organism Pseudomonas. Finally, a technoeconomic analysis highlighted potential economic advantages to AC when compared to water-chilling (WC) in facility locations where water costs are a more significant factor than energy costs. Conclusions. In this pilot study, AC chilling methods resulted in a superior product compared to WC methods and may have economic advantages in regions of the U.S. where water is expensive. As a next step, a similar experiment should be done in an industrial setting to confirm these results generated in a small-scale university lab facility.
Persistent SARS-COV-2 RNA positivity in a patient for 92 days after disease onset
Authors: Wang Junxue , Hang Xiaofeng , Wei Bo , Li Dingchen , Chen Fangyan , Liu Wei , Yang Chaojie , Miao Xiaohui , Han Li
Published: June 2020

Background: Recently, patients with COVID-19 who showed persistently positive SARS-CoV-2 nucleic acid test results despite resolved clinical symptoms have attracted a lot of attention. We report the case of a patient with mild symptoms of coronavirus disease (COVID-19), who achieved clinical recovery but showed persistently positive SARS-CoV-2 nucleic acid test results until Day 92 after disease onset.Case presentation: The patient is a 50-year-old man with mild symptoms of coronavirus disease (COVID-19). He was quarantined for 105 days. Of these, inpatient quarantine lasted for 75 days. When the nucleic acid test results were negative for 3 consecutive days, the patient was discharged at Day 75 after disease onset. During this period, multiple samples were collected from the patient’s body surface, the surrounding environment, and physical surfaces, but none of these tested positive for SARS-CoV-2. These samples included those from anal swabs, hands, inner surface of mask, cell phone, bed rails, floor around the bed, and toilet bowl surface. However, nucleic acid retest results on Day 80 and Day 92 after disease onset were positive for SARS-CoV-2 nucleic acids. The patient continued with quarantine and observation at home. After the test results on Days 101 and 105 after disease onset were negative, quarantine was terminated at last.Conclusion: Per our knowledge, this is the longest known time that a patient has tested positive for SARS-CoV-2 nucleic acids. No symptoms were observed during follow-up. During hospitalization, the SARS-CoV-2 nucleic acid positivity was not observed in samples from the body surface and surrounding environment, and no verified transmission event occurred during the quarantine at home. After undergoing clinical recovery a minority of patients with COVID-19 have shown long-term positive results for the presence of the SARS-CoV-2 nucleic acid. This has provided new understanding and research directions for coronavirus infection. Long-term follow-up and quarantine measures have been employed for such patients. Further studies are required to analyze potential infectivity in such patients and determine whether more effective antiviral drugs or regimens to enable these patients to completely clear viral infection should be researched.
Barriers to disclosure of violence against women in health services in Palestine: qualitative interview-based study
Authors: evans maggie , Shaheen Amira , feder gene , bacchus loraine , colombini manuela , ashkar suzy , alkaiyat abdulsalam
Published: June 2020

Background
Violence against women (VAW) damages health and requires a global public health response and engagement of clinical services. Recent surveys show that 27% of married Palestinian women experienced some form of violence from their husbands over a 12 month’s period, but only 5% had sought formal help, and rarely from health services. Across the globe, barriers to disclosure of VAW have been recorded, including self-blame, fear of the consequences and lack of knowledge of services. This is the first qualitative study to address barriers to disclosure within health services for Palestinian women.
Methods
In-depth interviews were carried out with 20 women who had experienced violence from their husbands. They were recruited from a non-governmental organisation offering social and legal support. Interviews were recorded, transcribed and translated into English and the data were analysed thematically.
Results
Women encountered barriers at individual, health care service and societal levels. Lack of knowledge of available services, concern about the health care primary focus on physical issues, lack of privacy in health consultations, lack of trust in confidentiality, fear of being labelled ‘mentally ill’ and losing access to their children were all highlighted. Women wished for health professionals to take the initiative in enquiring about VAW. Wider issues concerned women’s social and economic dependency on their husbands which led to fears about transgressing social and cultural norms by speaking out. Women feared being blamed and ostracised by family members and others, or experiencing an escalation of violence.
Conclusions
Palestinian women’s agency to be proactive in help-seeking for VAW is clearly limited. Our findings can inform training of health professionals in Palestine to address these barriers, to increase awareness of the link between VAW and many common presentations such as depression, to ask sensitively about VAW in private, reassure women about confidentiality, and increase awareness among women of the role that health services can play in VAW.
Assessment of the risk of permanent stoma after low anterior resection in rectal cancer patients
Authors: Zeman Marcin , Czarnecki Marek , Chmielarz Andrzej , Idasiak Adam , Grajek Maciej , Czarniecka Agnieszka
Published: June 2020

BackgroundOne of the most severe complications of low anterior resection is anastomotic leakage (AL). The creation of a loop ileostomy (LI) reduces the frequency of AL requiring surgical intervention, but up to one-third of temporary stomas may never be closed.The first aim of the study is to perform a retrospective assessment of the impact of LI on the risk of permanent stoma (PS) and symptomatic AL. The second aim of the study is to assess preoperative PS risk factors in patients with LI.MethodsA total of 286 consecutive patients who underwent low anterior resection were subjected to retrospective analysis. In 101 (35.3%) patients, diverting LI was performed due to low anastomosis, while in the remaining 185 (64.7%) patients, no ileostomy was performed. LIs were reversed after adjuvant treatment. Analyses of the effect of LI on symptomatic AL and PS were performed. Among the potential risk factors for PS, clinical factors and values ​​of selected peripheral blood parameters were analysed.ResultsPS occurred in 37.6% and 21.1% of the patients with LI and without LI, respectively (p <0.01). Symptomatic ALs were significantly more common in patients without LI. In this group, symptomatic ALs occurred in 23.8% of patients, while in the LI group, they occurred in 5% of patients (p <0.001). In the LI group, the only significant risk factor for PS in multivariate analysis was preoperative plasma fibrinogen concentration (OR = 1.008, 97.5% CI 1.003-1.014, p = 0.003).ConclusionsProtective LI significantly reduces the incidence of symptomatic AL, but a higher risk of PS is observed in this group of patients. The preoperative serum fibrinogen concentration is a risk factor for PS in LI patients and may be a helpful variable in decision models.
Effect of Bacillus Subtilis Protease on Growth, Production Performance and Feed Efficiency of Silkworm, Bombyx Mori L
Authors: Sun Linghong , Khalid Anam , Khalid Fatima , Wang Zaigui
Published: June 2020

Background:The effects of Bacillus subtilis protease on the silkworm (Bombyxmori L) production performance and feed efficiency were investigated. 2250 silkworms were randomly divided into two groups, the test group and the control group, each group had three replicates. A certain concentration of protease was sprayed to the mulberry leaves of the test group, while equal volume of deionized water was sprayed to the control group. Test diets were fed in three phases: 3rd instar, 4th instar and 5th instar larval stage.Results: The results demonstrated that: (i) final weight (FW), average daily gain (ADG), average daily feed intake(ADFI), and feed conversion ratio (FCR) in 4th and 5th larval instar, (ii) midgut protease activity, crude protein digestibility (CPD), crude fiber digestibility (CFD) and cocoon shell conversion rate (CSCR) (iii) the total number of bad cocoons,coarse cocoon, average pupa weight (APW), average cocoon shell weight (ACSW) and average cocoon weight (ACW) were extremely significantly higher (P<0.01) in test group as compared to control group. While, (i) the digestibility of crude lipid (EED) and (ii) the fly larvae cocoons in test group were higher significantly (P<0.05) than that of the control group. Conclusion:These results indicated that the B. subtilis protease could enhance the silkworm growth performance, feed efficiency and the cocoon quality of silkworm.
Two case reports of rare diseases occurring in rare parts: Splenic vein solitary fibrous tumor and Liver solitary fibrous tumor
Authors: Wang Wenjing , Bao Banghe , Hu Anbin , Zhu Xiaofeng , Chen Qing
Published: June 2020

Background
Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchyme. Two cases of SFT we report right now occurred in the splenic vein and liver respectively, this primary splenic vein SFT may be the first report case, and also the first report of liver recurrence SFT cured by orthotopic liver transplantation (OLT).
Case presentation
One case was a 37-year-old female patient whose primary tumor site was located in the splenic vein, which resulted in splenomegaly and hypersplenism; its recurrence again and again after surgical resection and eventually transferred to the liver, during 10 years of follow-up, 4 operations were performed, and he is in a good condition right now. The second case was a 54-year-old male patient whose primary tumor site was located in the liver, spleen and left side of the chest wall; however, he had no uncomfortable symptoms. Surgeons performed two operations to remove these tumors, totally. 6 years later, SFT recurrence in the liver, and given that the tumor was so large that it could not be completely surgical resected, we chose orthotopic liver transplantation (OLT), and no tumor recurrence during 12-month follow-up.
Conclusion
The reports of these two cases of SFT are very rare, especially the splenic vein SFT, which expand the understanding of SFT. The main treatment of SFT is still surgical resection, right now, and liver transplantation may be a new option treatment for the huge liver SFT.
A Randomized Clinical Trial on Acupuncture Versus Best Medical Therapy in Episodic Migraine Prophylaxis: The Acumigran Study
Authors: Giannini Giulia , Favoni Valentina , Merli Elena , Nicodemo Marianna , Torelli Paola , Matrà Annunzio , Giovanardi Carlo Maria , Cortelli Pietro , Pierangeli Giulia , Cevoli Sabina
Published: June 2020

BackgroundA large corpus of evidence has reported encouraging results for acupuncture as a prophylaxis therapy of migraine. However, trails investigated the efficacy of acupuncture in comparison to pharmacological treatment in episodic migraine showed conflicting results. The aim of the study was to evaluate if acupuncture is as effective as evidence based pharmacological drugs in episodic migraine prophylaxis. MethodsThis is a randomized controlled clinical study. Patient suffering from migraine without preventive treatment in the past three months were recruited. After the run-in period, episodic migraineurs were assigned randomly to two groups: the acupuncture group (A) was treated with 12 sessions of acupuncture and the pharmacological group (B) was treated with the most appropriate medication for each patient. Headache frequency was compared at baseline and at the end of treatment. Both groups were evaluated 3- and 6-months after treatment.ResultsA total of 148 patients (24 males and 124 females) were enrolled in the study. Out of these, 69 were randomized to A and 66 to B. At baseline no significantly differences were found between the two groups. The 15.5% of patients (21/135) interrupted the treatment, especially those randomized to B. After 4 months, the migraine frequency decreased from 8.58 ± 3.21 to 6.43 ± 3.45 in A and from 8.29 ± 2.72 to 6.27 ± 4.01 in B. Headache frequency decreased significantly after treatment without differences between the two groups (time-effect: p<0.001; group effect: p=0.332; interaction time-group effects: p=0.556). About 34% of patients showed a reduction of headache days by at least 50% after the treatment. The improvements observed at the end of treatment persisted in 57.3% (59/103) after 3 months and in 38.8% (40/103) after 6 months, especially in patients randomized to A.ConclusionsOur trial is the first one comparing acupuncture with the more appropriate pharmacological treatment for migraine prophylaxis. Data suggested that acupuncture could be adopted as a migraine prophylaxis and seem to be slightly superior to pharmacological treatment in compliance and rate of adverse events.
Genome-wide Transcriptome Study in Skin Biopsies Reveals an Association of E2F4 With Cadasil and Cognitive Impairment
Authors: Muiño Elena , Maisterra Olga , Jiménez-Balado Joan , Cullell Natalia , Carrera Caty , Torres-Aguila Nuria P , Cárcel-Márquez Jara , Gallego-Fábrega Cristina , Lledós Miquel , González-Sánchez Jonathan , Olmos-Alpiste Ferran , Espejo Eva , March Álvaro , Pujol Ramón , Rodríguez-Campello Ana , Romeral Gemma , Krupinski Jurek , Martí-Fábregas Joan , Montaner Joan , Roquer Jaume , Fernández-Cadenas Israel
Published: June 2020

Background:CADASIL is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the receptor, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, as executive function is characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further.Methods:Agenome-wide transcriptome study(four casespaired with three healthysiblings)was carried out,in addition toa qRT-PCR for validation purposes(ten new cases and eight new controls).Neuropsychological tests were performedto evaluateverbal memory, attention and information processing speed (IPS), motor speed and dexterity, executive function and visuoconstructional skills. The Single-nuclei Brain RNA-seq expression browser (SNBREB) and the GTExPortalwere used to study brain expressionof the significant mRNAs found.Results: The two most significant differentially expressed mRNAs (BANP,p-value=7.23x10-4 and PDCD6IP, p-value=8.36x10-4) were selected for the validation study by qRT-PCR. Additionally, we selectedtwo more mRNAs(CAMK2G,p-value=4.52x10-3 and E2F4, p-value=4.77x10-3) due to their association with ischemic neuronal death. E2F4showed differential expression in the genome-wide transcriptome study and in the qRT-PCR (p=1.23x10-3), and it was upregulated in CADASIL cases. Furthermore, higher E2F4 expressionwas associated with worseexecutive function (p=2.04x10-2) and attention and IPS (p=8.73x10-2).In silico studies indicated that E2F4 is expressed in brain endothelial cells. Conclusions:Skin biopsies of CADASIL patients presented higher mRNA levels of E2F4and these higher levels have a significant correlation with worseexecutive function and IPS.
Analysis of key genes and pathways associated with pathogenesis of intervertebral disc degeneration
Authors: Hu Shiyu , Fu Yucheng , Yan Bin , Shen Zhe , Lan Tao
Published: June 2020

Background: Intervertebral disc degeneration (IDD) is widely known as a main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. The aim of this study is to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD.
Material/Methods: The gene expression data of GSE23130 was downloaded and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. In addition, Protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module.
Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs mainly enriched in regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most of DEGs were primarily enriched in PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1.
Conclusions: In summary, key candidate genes and pathway were identified by using integrated bioinformatics analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.
Role of Temporal Discounting in a Conditional Cash Transfer (CCT) Intervention to Improve Engagement in the Prevention of Mother-to-Child Transmission (PMTCT) Cascade
Authors: Saleska Jessica Londeree , Turner Abigail Norris , Gallo Maria F. , Shoben Abigail , Kawende Bienvenu , Ravelomanana Noro Lantoniaina Rosa , Thirumurthy Harsha , Yotebieng Marcel
Published: June 2020

Background: Temporal discounting (TD), the tendency of individuals to discount future costs and benefits relative to the present, is often associated with greater engagement in risky behaviors. Incentives such as conditional cash transfers (CCTs) have the potential to counter the effects of TD on health behaviors. We hypothesized that CCTs work by mitigating the effects of high TD, measured using a delay-discounting task.Methods: We conducted an interaction analysis using data from a randomized trial of a CCT intervention among 434 HIV-positive pregnant women in the Democratic Republic of Congo. The analysis focused on two outcomes: 1) retention in HIV care, and 2) uptake of prevention of mother-to-child transmission (PMTCT) services.Results: The effect of TD on retention was small, and we did not observe evidence of interaction between TD and CCT on retention. However, our findings suggest that CCT may mitigate the negative effect of high TD on uptake of PMTCT services (interaction contrast (IC): 0.18, 95% CI: -0.09, 0.44).Conclusions: Our findings support the continued use of small, frequent incentives, to motivate improved uptake of PMTCT services, especially among women exhibiting high TD.CONTRIBUTIONS TO THE LITERATURE· Conditional cash transfer (CCT) interventions demonstrate varying degrees of effectiveness in improving engagement in HIV care. Understanding how these interventions work allow for better adaptation in different contexts, though few studies have explored the underlying mechanisms of CCT.· We assessed whether CCT works by mitigating the effect of temporal discounting on disengagement from care, a major posited mechanism of the intervention, among HIV infected pregnant and breastfeeding women in the Democratic Republic of Congo. · Our findings contribute to gaps in literature surrounding the role of temporal discounting, and its mitigation by CCT, on engagement in HIV care.
Hierarchy in the Avidity and Cross-reactivity of Anti-citrullinated Protein Antibodies in the Serum of Patients With Rheumatoid Arthritis
Authors: Haraguchi Akihisa , Yamada Hisakata , Sakuragi Takahide , Tsuru Tomomi , Kondo Masakazu , Nakashima Yasuharu
Published: June 2020

BackgroundFine specificity of anti-citrullinated protein antibodies (ACPAs), in which cross-reactivity exists, varies among patients with rheumatoid arthritis (RA), but it is unclear whether the mechanism of ACPA production is same or different among individuals. Since avidity of serum antibody reflects the direction of immune response, we compared the levels of avidity and cross-reactivity between various ACPAs in a cohort of RA patient.MethodsSera from 180 RA patients positive for anti-cyclic citrullinated peptide (CCP) 2 antibody were screened for positivity of antibodies against CCP1, and citrullnated fibrinogen (cFib), enolase (cEno), and vimentin (cVim) peptides. Avidity of the four ACPAs, and some autoantibodies and antibodies against foreign antigens was determined by an elution assay using sodium thiocyanate solution. Cross-reactivity between different ACPAs was estimated by measuring the inhibition of binding by competitor peptides. ResultsThe prevalence of anti-CCP1, anti-cFib, anti-cEno, and anti-cVim antibodies in the anti-CCP2-positive RA cohort were 37.7%, 38.3%, 15.6%, and 23.9%, respectively. The avidity of ACPAs, except for anti-cVim antibody, was significantly lower than that of antibodies against foreign antigens, while there was a large variety in the avidity of other autoantibodies. At individual levels, the avidity of anti-cVim was significantly higher than that of other ACPAs, and there was a significant correlation in the avidity of anti-CCP and anti-cFib antibodies. Substantial extent of cross-reactivity was seen between different ACPAs, which also showed a fixed hierarchy.ConclusionThe fixed hierarchy in the avidity and cross-reactivity between different ACPAs suggests that the mechanism underlying ACPA production is common to all RA patients. Presence of a dominant antigen that induces whole ACPA response is speculated.
Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells
Authors: Cao Yu , Liu Juxiong , Zhang Qing , Ma Lijun , Wang Jiaxin , Li Wen , Ge Yusong , Cheng Ji , Yang Zhanqing , Fu Shoupen
Published: June 2020

Background Kp-10 is a peptide hormone mainly involved in the initiation tissue development in puberty. Recent studies have shown that Kp-10 is involved in fat synthesis. However, the role of Kp-10 in milk fat synthesis in lactating dairy cows has not been reported. Therefore, this study investigated the correlation between GPR54 and milk fat synthesis in dairy cows and to study the underlying mechanism in BMECs. Results The results showed that the expression of GPR54, SREBP1 and FASN in mammary glands of high-milk fat dairy cows were significantly higher than those in mammary glands of low-milk fat dairy cows. Meanwhile, 10nM Kp-10 can significantly inhibit AMPK/SIRT6 signaling pathway and promote milk fat synthesis in BMECs through its receptor GPR54. Overexpression of SIRT6 significantly reduced the acetylation level of SREBP1 and milk fat synthesis in BMECs.Conclusions These results suggested that Kp-10 inhibits the AMPK / SIRT6 signaling pathway by mediating GPR54, thereby increasing SREBP1 acetylation levels and increasing milk fat synthesis in BMECs.