bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association of Sex-biased ATRX&nbsp;Mutation in Female Gastric Cancer Patients With Enhanced Immunotherapy-related Anticancer Immunity&nbsp;&nbsp;
Authors: Ge You , Wei Feiran , Du Guoping , Fei Gaoqiang , Li Wei , Li Xiaoshan , Chu Jinjin , Wei Pingmin 
Published: November 2020

Abstract
Background: Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy. Methods: Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM). Results: ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455-0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596-1.362, P = 0.712). Conclusions: ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.
The Safety and Efficacy of the Interleukin-1 Antagonist Anakinra in Severe Cases of COVID-19- A Systematic Review and Meta-analysis.
Authors: Somagutta Manoj Kumar Reddy , Pormento Maria Kezia Lourdes , Hamid Pousette , Hamdan Alaa , Khan Muhammad Adnan , Desir Rockeven , Vijayan Rupalakshmi , Shirke Saloni , Jeyakumar Rishan , Dogar Zeryab , Makkar Sarabjot Singh , Guntipalli Prathima , Ngaba Neguemadji Ngardig , Nagineni Manasa Sindhura , Paul Trissa , Luvsannyam Enkhmaa , Riddick Chala 
Published: November 2020

Abstract
This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease in 2019 (COVID-19). PubMed, Google Scholar, Cochrane Library, Embase, Scopus, medRxiv, and bioRxiv were searched. Three retrospective studies and five case series involving 3,274 adult patients with severe COVID-19 were included, 621 treated with anakinra (whether administered alone or in combination with other drugs) and 1,565 in the control group arm. All-cause mortality of severe COVID-19 patients among the anakinra group was 20% (16/81), which was lower than that in the control group (65%; 39/60). The difference was statistically significant [hazard ratio (HR) = 0.13, 95% confidence interval (CI) 0.06–0.29, I2= 0%]. The mechanical ventilation requirement with OR 0.57 (0.11-2.84, I2=87%) was not significantly better compared to the control group. For the safety of anakinra, we evaluated thromboembolism risk and liver enzyme elevation. Thromboembolism risk with OR: 1.48 (0.55- 3.99, I2=0%) and elevation in liver transaminases with OR 0.67 (0.11-3.93, I2=66%) were not statistically significant over the control group. However, these non-significant differences between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.
The Safety and Efficacy of the Interleukin-1 Antagonist Anakinra in Severe Cases of COVID-19- A Systematic Review and Meta-analysis.
Authors: Somagutta Manoj Kumar Reddy , Pormento Maria Kezia Lourdes , Hamid Pousette , Hamdan Alaa , Khan Muhammad Adnan , Desir Rockeven , Vijayan Rupalakshmi , Shirke Saloni , Jeyakumar Rishan , Dogar Zeryab , Makkar Sarabjot Singh , Guntipalli Prathima , Ngaba Neguemadji Ngardig , Nagineni Manasa Sindhura , Paul Trissa , Luvsannyam Enkhmaa , Riddick Chala , Pagad Sukrut , Sanchez-Gonzalez Marcos 
Published: November 2020

Abstract
This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease in 2019 (COVID-19). PubMed, Google Scholar, Cochrane Library, Embase, Scopus, medRxiv, and bioRxiv were searched. Three retrospective studies and five case series involving 3,274 adult patients with severe COVID-19 were included, 621 treated with anakinra (whether administered alone or in combination with other drugs) and 1,565 in the control group arm. All-cause mortality of severe COVID-19 patients among the anakinra group was 20% (16/81), which was lower than that in the control group (65%; 39/60). The difference was statistically significant [hazard ratio (HR) = 0.13, 95% confidence interval (CI) 0.06–0.29, I2= 0%]. The mechanical ventilation requirement with OR 0.57 (0.11-2.84, I2=87%) was not significantly better compared to the control group. For the safety of anakinra, we evaluated thromboembolism risk and liver enzyme elevation. Thromboembolism risk with OR: 1.48 (0.55- 3.99, I2=0%) and elevation in liver transaminases with OR 0.67 (0.11-3.93, I2=66%) were not statistically significant over the control group. However, these non-significant differences between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.
Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: A potential role in severe COVID-19
Authors: Li Hsin-Hsien , Liu Chen-Chi , Hsu Tien-Wei , Lin Jiun-Han , Hsu Jyuan-Wei , Li Anna Fen-Yau , Yeh Yi-Chen , Hsu Han-Shui , Hung Shih-Chieh 
Published: November 2020

Abstract
Background: Air pollution and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after COVID-19 infection, but the underlying mechanisms are not well exploited. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.Results: In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1)+ lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-inuced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL‐8, or treatment with reparixin, an inhibitor of IL‐8 receptors CXCR1/2.Conclusions: These data suggest that poor prognosis after COVID-19 infection caused by air pollution and IPF is mediated through upregulation of ACE2 and TMPRSS2 in pulmonary fibroblasts, which can be prevented by blocking the IL-8/CXCR1/2 pathway.
Autistic traits and gender modulate emotion changes before and during the COVID-19 outbreak: a preliminary evidence based on quasi-experimental design
Authors: Zhao Xudong , Zhao Binglei , Li Wenrui , Cai Yang , Shi Wendian , Li Chunbo 
Published: November 2020

Abstract
Individuals with autism spectrum disorder (ASD) show an enhanced response to stressors, and gender plays an important role in stress response. Thus, autistic traits (ATs) in the general population and gender may regulate the emotion changes before and during the outbreak of COVID-19. The present study addressed this issue through a participants between quasi-experimental design, in which the epidemic status (before, during), gender (male, female), and AT groups (high ATs, low ATs) were independent variables, and positive and negative emotions were dependent variables. We used generalized linear models to estimate the effects of the independent variables and their interactions on emotions. The results showed that the COVID-19 outbreak reduced positive emotions and increased fear and anger. Furthermore, compared with before the COVID-19 outbreak, individuals with high ATs and females experienced stronger anger and fear than individuals with low ATs and males during the epidemic. The present study revealed the emotional impacts of COVID-19 and greater emotional susceptibility to COVID-19 pandemic among individuals with high ATs and females. Our findings provide prospective evidence for understanding the ASD/ATs-related enhanced response to pathogen threat-related stressors and have implications for COVID-19 crisis interventions.
Candida tropicalis distribution and drug resistance is correlated with ERG11 and UPC2 expression
Authors: Wang Dan , An Na , Yang Yuwei , Yang Xianggui , Fan Yingzi , Feng Jiafu 
Published: November 2020

Abstract
Background: Candida tropicalis (C. tropicalis) is an important opportunistic pathogenic Candida species that can cause nosocomial infection. In this study, we analyzed the distribution and drug susceptibility of C. tropicalis and the relationship between ERG11 and UPC2 expression and resistance to azole antifungal agents.Methods: C. tropicalis was cultured and identified by Sabouraud Agar Medium, CHROM Agar Candida and ATB tests (Bio-Mérieux, France). Total RNA was extracted from the collected strains, and the ERG11 and UPC2 mRNA expression levels were analyzed by quantitative real-time PCR.Results: In total, 2872 clinical isolates of Candida, including 319 strains of C. tropicalis, were analyzed herein; they were mainly obtained from the Departments of Respiratory Medicine and ICU. The strains were predominantly isolated from airway secretion samples, and the detection trend in four years was mainly related to the type of department and specimens. The resistance rates of C. tropicalis to fluconazole, itraconazole and voriconazole had been increasing year by year. The mRNA expression levels of ERG11 and UPC2 in the fluconazole-resistant group were significantly higher than they were in the susceptible group. In addition, there was a significant positive linear correlation between these two genes in the fluconazole-resistant group.Conclusions: Overexpression of the ERG11 and UPC2 genes in C. tropicalis could increase resistance to azole antifungal drugs. The routine testing for ERG11 and UPC2 in high-risk patients in key departments would provide a theoretical basis for the rational application of azole antifungal drugs.
Exploring health-seeking behaviour among adolescent mothers during the Ebola epidemic in Western rural district of Freetown, Sierra Leone
Authors: Massaquoi Hamida , Atuhaire Catherine , Chinkonono Gorgeous Sarah , Christensen Betty Nyawira , Bradby Hannah , Cumber Samuel Nambile 
Published: November 2020

Abstract
Background: From 2014-2016, the largest Ebola outbreak in history threatened Sierra Leone and its neighbouring countries, Guinea and Liberia. The Ebola outbreak impacted pregnant adolescent girl’s access to prenatal care during the pandemic. The aim of the study is to understand health-seeking behaviour among adolescent mothers who were pregnant during the Ebola epidemic in Waterloo, Sierra Leone. Methods: The present qualitative study uses the “Three Delay” model, as a theoretical framework to understand and explore adolescent mother’s health-seeking behaviour through four focus group discussions with five participants in each discussion group. The data were analysed using thematic analysis. Results: A multitude of challenges were identified following the Ebola epidemic. The fear of contracting Ebola was a common reason for not seeking care or utilising services. This notion was perpetuated by perceptions in the community and participants personal experiences. Quarantines, national lockdowns, roadblocks, loss of income and extreme poverty were also identified as barriers to accessing health facilities during Ebola. The different encounters with health workers and the challenges that arose at the health facilities were subsequently additional discouraging factors influencing participant’s decision not to seek health care. Conclusion: Many of the pre-existing maternal health, societal and social-economic challenges were exacerbated during the Ebola. The epidemic also contributed new challenges such as public fear, mistrust towards health professionals and the health system. Greater emphasis needs to be placed on improving maternal care in general, but also improving preparedness for maternal care in case of future outbreaks, especially for the most vulnerable groups such as adolescent mothers.
Host reproductive cycle influences the pouch microbiota of wild Southern Hairy-nosed Wombats (Lasiorhinus latifrons)
Authors: Weiss Sesilje , Taggart David , Smith Ian , Helgen Kristofer M , Eisenhofer Raphael 
Published: November 2020

Abstract
Background: Marsupials are born much earlier than placental mammals, with most crawling from the birth canal to the protective marsupium (pouch) to further their development. However, little is known about the microbiology of the pouch and how it changes throughout a marsupial’s reproductive cycle. Here, using stringent controls, we characterized the microbial composition of multiple body sites from 26 wild Southern Hairy-nosed Wombats (SHNWs), including pouch samples from animals at different reproductive stages. Results: Using qPCR of the 16S rRNA gene we found higher concentrations of microbial DNA in the pouch than in negative controls. We observed significant differences in microbial composition and diversity between the body sites tested, as well as between pouch samples from different reproductive stages. The pouches of reproductively active females had drastically lower microbial diversity (mean richness 19) compared to reproductively inactive females (mean richness 941), and were dominated by gram positive bacteria from the Actinobacteriota phylum (81.7-90.6%), with the dominant families classified as Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, and Dietziaceae. Three of the five most abundant sequences identified in reproductively active pouches had closest matches to microbes previously isolated from tammar wallaby pouches. Conclusions: This study represents the first contamination controlled investigation into the marsupial pouch microbiota, and sets a rigorous framework for future pouch microbiota studies. Our results suggest that SHNW pouches contain communities of microorganisms that are substantially altered by the host reproductive cycle. We recommend further investigation into the roles that pouch microorganisms may play in marsupial reproductive health and joey survival.
Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis
Authors: Chen Caizhi , Feng Yeqian , Wang Jingjing , Liang Ye , Zou Wen 
Published: November 2020

Abstract
Background: The snoRNA host gene SNHG15 produces a long non‐coding RNA (lncRNA) with a short half-life and has been reported to be dysregulated in multiple cancers and has recently been found to be correlated with tumour progression. Therefore, this meta-analysis was performed to evaluate the generalised prognostic role of small nucleolar RNA host gene 15 (SNHG15) in malignancies, based on variable data from different studies. Methods: Four public databases were used to identify eligible studies. The association between prognostic indicators and clinical features was extracted and pooled to estimate the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was measured using Begg’s test and Egger’s test, and the stability of pooled results were measured using sensitivity analysis. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was screened to further validate our results. Ultimately, we predicted the molecular regulation of SNHG15 based on the public databases.Results: In total, 11 studies including 1,087 patients were ultimately enrolled in our meta-analysis. We found that SNHG15 overexpression was associated with worse overall survival (OS) and disease-free survival (DFS), and this was validated in the Gene Expression Profiling Interactive Analysis (GEPIA) cohort. Moreover, increased SNHG15 expression suggested advanced TNM stage and LNM, but was not associated with age, gender, or tumour size. No publication bias or instability of the results was observed. SNHG15 was significantly upregulated in seven cancers and elevated expression of SNHG15 indicated shorter OS and DFS in five malignancies based on the validation using the GEPIA cohort. Further functional prediction indicated that SNHG15 may participate in some cancer-related pathways.Conclusions: Upregulation of lncRNA SNHG15 was notably associated with worse prognosis and clinical features, suggesting that SNHG15 might serve as a novel prognostic factor in various cancers.
Investigation of the effect of Delayed Auditory Feedback and transcranial Direct Current Stimulation (DAF-tDCS) treatment for the enhancement of speech fluency in adults who stutter: a Randomized Controlled Trial
Authors: Moein Narges , Mohamadi Reyhane , Rostami Reza , Nitsche Michael , Zomorrodi Reza , Ostadi Amir , Keshtkar Abbasali 
Published: November 2020

Abstract
Background: With a population prevalence of one percent, stuttering is among the main speech pathology-related topics of research. Adults who stutter may benefit from transcranial direct current stimulation (tDCS) as an adjunctive intervention for enhancing speech fluency. In this study, Delayed Auditory Feedback (DAF) was combined with tDCS applied over the superior temporal gyrus. It was anticipated that the combined intervention cause improvements in speech fluency.Methods: A randomized, double-blind, sham-controlled clinical trial was conducted to investigate the effectiveness of intervention in enhancing speech fluency. Fifty participants were randomly allocated to the intervention or control group. In the intervention group, participants received DAF combined with anodal tDCS, while the control group was exposed to sham tDCS simultaneously with DAF. Each subject participated in six intervention sessions. Speech fluency was assessed as the baseline, before intervention as well as immediately, one week and six weeks after intervention. Results: In the intervention group, the percentage of stuttered syllables was significantly reduced immediately, one week and six weeks after the intervention, as compared with the control group. The scores of the Stuttering Severity Instrument, also showed a significant reduction in the intervention group compared with the control group. No significant difference was found in the Overall Assessment of the Speaker’s Experience of Stuttering questionnaire scores between the two groups after intervention. Conclusion: The results of this study propose anodal tDCS as an adjunctive method to increase speech fluency in stuttering for a prolonged time course after intervention, when combined with fluency therapy.Trial registration: This trial was registered in ClinicalTrial.gov before recruiting the subjects. The registration number is NCT03990168 and the date of registration is June 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03990168
A 15 Month Experience with a Primary Care-based Telemedicine Screening Program for Diabetic Retinopathy.
Authors: Benjamin James , Sun Justin , Cohen Devon , Matz Joseph , Barbera Angela , Henderer Jeffrey , Cheng Lorrie , Grachevskaya Julia , Shah Rajnikant , Zhang Yi 
Published: November 2020

Abstract
Background: Using telemedicine for diabetic retinal screening is becoming popular especially amongst at-risk urban communities with poor access to care. The goal of the diabetic telemedicine project at Temple University Hospital is to improve cost-effective access to appropriate retinal care to those in need of close monitoring and/or treatment.Methods: This will be a retrospective review of 15 months of data from March 2016 to May 2017. We will investigate how many patients were screened, how interpretable the photographs were, how often the photographs generated a diagnosis of diabetic retinopathy (DR) based on the screening photo, and how many patients followed-up for an exam in the office, if indicated.Results: Six-hundred eighty-nine (689) digital retinal screening exams on 1377 eyes of diabetic patients were conducted in Temple’s primary care clinic. The majority of the photographs were read to have no retinopathy (755, 54.8%). Among all of the screening exams, 357 (51.8%) triggered a request for a referral to ophthalmology. Four-hundred forty-nine (449, 32.6%) of the photos were felt to be uninterpretable by the clinician. Referrals were meant to be requested for DR found in one or both eyes, inability to assess presence of retinopathy in one or both eyes, or for suspicion of a different ophthalmic diagnosis. Sixty-seven patients (9.7%) were suspected to have another ophthalmic condition based on other findings in the retinal photographs. Among the 34 patients that were successfully completed a referral visit to Temple ophthalmology, there was good concordance between the level of DR detected by their screening fundus photographs and visit diagnosis.Conclusions: Although a little more than half of the patients did not have diabetic eye disease, about half needed a referral to ophthalmology. However, only 9.5% of the referral-warranted exams actually received an eye exam. Mere identification of referral-warranted diabetic retinopathy or other eye disease is not enough. A successful telemedicine screening program must close the communication gap between screening and diagnosis by reviewer to provide timely follow-up by eye care specialists.