bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of metabolic and stress responses during subtoxic expression of the type I toxin hok in Erwinia amylovora
Authors: Peng Jingyu , Triplett Lindsay R. , Sundin George 
Published: January 2021

Abstract
Background: Toxin-antitoxin (TA) systems, abundant in prokaryotes, are composed of a toxin gene and its cognate antitoxin. Several toxins are implied to affect the physiological state and stress tolerance of bacteria in a population. We previously identified a chromosomally encoded hok-sok type I TA system in Erwinia amylovora, the causative agent of fire blight disease on pome fruit trees. A high-level induction of the hok gene was lethal to E. amylovora cells through unknown mechanisms. The molecular targets or regulatory roles of Hok were unknown.Results: Here, we examined the physiological and transcriptomic changes of Erwinia amylovora cells expressing hok at subtoxic levels that were confirmed to confer no cell death, and at toxic levels that resulted in killing of cells. In both conditions, hok caused membrane rupture and collapse of the proton motive force in a subpopulation of E. amylovora cells. We demonstrated that induction of hok resulted in upregulation of ATP biosynthesis genes, and caused leakage of ATP from cells only at toxic levels. We showed that overexpression of the phage shock protein gene pspA largely reversed the cell death phenotype caused by high levels of hok induction. We also showed that induction of hok at a subtoxic level rendered a greater proportion of stationary phase E. amylovora cells tolerant to the antibiotic streptomycin. Conclusions: We characterized the molecular mechanism of toxicity by high-level of hok induction and demonstrated that low-level expression of hok primes the stress responses of E. amylovora against further membrane and antibiotic stressors.
ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
Authors: Zhu Hai , Wang Gang , Zhu Haixing , Xu Aman 
Published: January 2021

Abstract
Background: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear.Methods: The expression level of ITGA5 was detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER, immunohistochemistry (IHC) staining and western blot were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape.Results: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal tumors. Interestingly, immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining and western blot further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 was mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”.Conclutions: Our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.
What do service providers in Southern Ethiopia say about barriers to using youth-friendly sexual and reproductive health services for adolescents?: Qualitative study&nbsp;
Authors: Habtu Yitagesu , Kaba Mirgissa , Mekonnen Hussen 
Published: January 2021

Abstract
Background: In Ethiopia, lowest utilization of adolescent friendly sexual and reproductive health services (AFSRHs) is recorded among Sub-Saharan African countries. Little is known why adolescents were not accessing the existing services to the side of healthcare providers. Objective: The aim of this study is to explore contextual perceived and actual barriers to accessing AFSRHs by adolescents in Southern Ethiopia.Methods: Phenomenological study design supplemented with observation was used to explore perceived and actual barriers to accessing AFSRHs in 2020. Criterion sampling was used to select study participants. In-depth interviews with key healthcare providers and non-specialist sexual and reproductive health providers were conducted. Transcribed interviews and observation were imported to Open Code 4.02 for coding, categorizing codes, and creating themes. Finally, barriers to assessing the services were explained using thematic analysis. Results: The study explores contextual barriers to accessing sexual and reproductive health services in five emergent themes. According to providers’ view, barriers include ranging from providers (e.g poor providers’ competency), health facility (e.g. supply constraints and unsupportive environment), adolescents (e.g perceived lack of information and attitude towards SRHs), community (e.g. lack of parental and social support), and broader health system (e.g. poor implementation and multi-sectorial engagement). Conclusion: As to providers, adolescents face multiple barriers to accessing youth friendly sexual and reproductive health services. Healthcare facilities and the health systems should implement varieties of approaches to increase access to the services for adolescents. The existing strategies should be re-evaluated and new interventions at all levels of the healthcare system are needed. Moreover, implementation research is required at system level factors.
Daily, Oral FMT for Longterm Maintenance Therapy in Ulcerative Colitis: Results of a single-center, prospective, randomized pilot study.
Authors: Crothers Jessica Wood , Chu Nathaniel D. , Nguyen Le Thanh Tu , Phillips Magen , Collins Cheryl , Fortner Karen , Rio-Geurra Roxana del , Lavoie Brigitte , Callas Peter , Velez Mario , Cohn Aaron , Elliott Ryan J. , Wong Wing Fei , Vo Elaine , Wilcox Rebecca , Smith Mark , Kassam Zain , Budd Ralph , Alm Eric J. , Mawe Gary M. , Moses Peter L 
Published: January 2021

Abstract
BackgroundFecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term fecal microbiota transplantation (FMT) in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). MethodsSubjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. ResultsTwelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral treatment. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. ConclusionThese pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.
Prevalence of Depression Symptoms and Associated Sociodemographic and Clinical Correlates among Syrian Refugees in Lebanon
Authors: Naal Hady , Nabulsi Dana , Arnaout Nour El , Abdouni Lina , Dimassi Hani , Harb Ranime , Saleh Shadi 
Published: January 2021

Abstract
Background: Since the outbreak of the Syrian war in 2011, close to 6 million Syrian refugees have escaped to Syria’s neighbouring countries, including Lebanon. Evidence suggests rising levels of mental health disorders among Syrian refugee populations. Yet, to the best of our knowledge, large-scale studies addressing the mental health of adult Syrian refugees in Lebanon are lacking.Aims: We examined the prevalence of depression symptoms, which represent a common and debilitating mental health disorder among Syrian refugee populations in Lebanon, along with their sociodemographic and clinical correlates.Methods: A cross-sectional survey design was conducted as part of a collaborative project-“Sijilli”- led by the Global Health Institute at the American University of Beirut (Beirut, Lebanon) across 4 informal tented settlements for refugees (Beirut, Bekaa, North, South) in Lebanon among adult Syrian refugees (≥18), over a period extending from 2018 to 2020. The survey inquired about participants’ sociodemographic and clinical characteristics, and screened participants for symptoms of depression through sequential methodology using the Patient Health Questionnaire (PHQ-2 and PHQ-9).Results: A total of 3255 adult Syrian refugees were enrolled in the study. Of those refugees, 46.73% (n=1521) screened positive on the PHQ-2 and were therefore eligible to complete the PHQ-9. In the entire sample (n=3255), the prevalence of moderate to severe depression symptoms (PHQ-2 ≥2 and then PHQ-9 ≥10) was 22% (n=706). Further analyses indicate that being ≥45 years of age (OR 1.61, 95% CI 1.13-2.30), a woman (OR 1.34, 95% CI 1.06-1.70), widowed (OR 2.88, 95% CI 1.31-6.32), reporting a neurological (OR 1.73, 95% CI 1.15-2.60) or a mental health condition (OR 3.98, 95% CI 1.76-8.97) are major risk factors for depression.Conclusion: Our study suggests that an estimated one in four Syrian refugees in Lebanon shows moderate to severe depression symptoms, and our findings have important public health and clinical implications on refugee health. There is a need to enhance screening efforts, to improve access and referral to mental health services, and to improve post-migration factors among Syrian refugees in Lebanon.
CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma
Authors: Liu Tao , Han Xiujuan , Zheng shutao , Liu Qing , Tuerxun Aerziguli , Zhang Qiqi , Yang Lifei , Lu Xiaomei 
Published: January 2021

Abstract
Background: Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. Method: Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9（Clustered regularly interspaced short palindromic repeats）was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib.Results: Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group.Conclusion: Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.
Investigating Metalinguistic Written Corrective Feedback Focused on EFL Learners' Discourse Markers Accuracy in Mobile-mediated Context
Authors: Pourdana Natasha , Nour Payam , Yousefi Fariba 
Published: January 2021

Abstract
Among a growing body of research that examined the contradictory role of written corrective feedback (WCF) in development of L2 writing accuracy, this study investigated the possible impact of focused metalinguistic WCF on discourse markers (DMs) in writing performance of an intact group of 42 Iranian English as a Foreign Language (EFL) learners over an eight-week period. In an authentic, situated, and personalized learning platform, giving and receiving WCF were made possible only through the mobile-mediated application of WhatsApp. Before participants wrote on selected elicitation topics, they had taken part in a 2004 version of Oxford Preliminary Test in order to be screened for their initial differences in writing performance. After receiving metalinguistic WCF on their scripts, participants were required to work on the coded feedback and try to eliminate the DM errors in their revised writing assignment. After collecting the scripts over an eight-week period, the content of written assignment was thematically analyzed using NVivo 21 Software for the additive, adversative, causal and temporal DMs, following Halliday and Hasan’s (1976) typology. In a convergent mixed-methods design, the content analysis of the qualitative data showed a larger distribution of additive DM than adversative, causal, and temporal DMs in all participants’ written scripts. Exploring the possible impact of metalinguistic WCF on improving the DMs accuracy, analysis of the frequency count data with Statistical Package for the Social Sciences (SPSS) multivariate Chi-square test reported the fluctuation and unsystematic patterns of distribution for four types of DMs with no sign of significant long-term improvement in DMs accuracy after receiving metalinguistic WCF. These findings implied further research on practicing alternative WCF strategies focused on variety of error types in actual and virtual L2 writing environments.
Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting Drugs
Authors: Xu Wei-long , Zhao Yan 
Published: January 2021

Abstract
Background: Lumbar disc degeneration (LDD) is a major pathological process implicated in low back pain. At present, the research in the fields of spinal surgery has highlighted the complex mechanisms underlying LDD, with autophagy being considered as one of the important processes involved.Objectives: This study was designed to identify the potential key genes and molecular pathways associated with LDD and autophagy using computational tools and publicly available data, and to explore drugs targeting the relevant genes associated with LDD and autophagy.Materials and Methods: We used text mining to detect the LDD and autophagy-associated genes, and the intersection of the two gene sets was selected for gene ontology analysis using the DAVID program. We then constructed protein–protein interaction networks, followed by a functional enrichment analysis, from which we obtained three significant gene modules. Finally, the final list of genes was queried against the Drug Gene Interaction database to find drug candidates targeting relevant genes associated with LDD and autophagy.Results: Our analysis identified 72 genes common to both the “LDD” and “Autophagy” text mining concepts. Gene enrichment analysis yielded three significant gene modules (22 genes), which represent four significant pathways and could be targeted by 32 Food and Drug Administration (FDA)-approved drug molecules, and identified the drug–gene interactions. Conclusion: In summary, we presented a method to explore the potential key genes, molecular pathways and candidate drugs associated with LDD and autophagy. As a result, in this method, we identified a total of 22 potential genes, four significant pathways and 32 candidate drugs, which could provides a basis for new trials and the development of novel targeted therapies as potential treatments for LDD.
Rapid ethnographic assessment for potential anti-malarial mass drug administration in an outbreak area of Santo Domingo, Dominican Republic
Authors: Keys Hunter , Ureña Keyla , Reyes Jhefres , Bardosh Kevin , Pell Christopher , Puello Jose , Blount Stephen , Noland Gregory S. 
Published: January 2021

Abstract
Background In the Dominican Republic, a recent outbreak of malaria in the capital, Santo Domingo, threatens efforts to eliminate the disease. Mass drug administration (MDA) has been proposed as one strategy to reduce transmission. The success of MDA is contingent upon high levels of acceptance among the target population. To inform the design of future MDA campaigns, this rapid ethnographic assessment examined malaria-related knowledge and attitudes toward malaria MDA among residents of a transmission focus in Santo Domingo. Methods In October 2019, a rapid ethnographic assessment was conducted in the Los Tres Brazos transmission focus, which had not previously received MDA. National malaria programme staff conducted 61 structured interviews with key informants, recorded observations, and held 72 informal conversations. Using a grounded theory approach, data were analysed during three workshop sessions with research team members. Results Among those who had heard of malaria in the structured interviews (n=39/61; 64%), understanding of the disease was largely based on personal experience from past outbreaks or through word-of-mouth. Community health workers (promotores) were trusted for health information and malaria diagnosis more so than professional clinicians. No participant (0%) was familiar with malaria MDA. After learning about MDA, almost all study participants (92%) said that they would participate, seeing it as a way to care for their community. Reasons for not participating in future MDA included not trusting drug administrators, feeling reluctant to take unprescribed medicine, and fear of missing work. Additional identified challenges to MDA included reaching specific demographic groups, disseminating effective MDA campaign messages, and managing misinformation and political influence. Conclusion Residents appear accepting of MDA despite a lack of prior familiarity. Successful MDA will depend on several factors: fostering relationships among community-based health workers, clinicians, community leaders, and others; developing clear health messages that use local terms and spreading them through a variety of media and social networks; and contextualizing MDA as part of a broader effort to promote community health.
Neonatal care practices in Buikwe District, Uganda: A qualitative study
Authors: Roed Marte Bodil , Engebretsen Ingunn Marie Stadkleiv , Mangeni Robert 
Published: January 2021

Abstract
Background: Sub-Saharan Africa is the region with the highest neonatal mortality rate, with Uganda reporting 20 deaths per 1000 live births. The Uganda Clinical Guidelines (UCG) from 2016 have detailed descriptions on care for mothers and their newborns during pregnancy, delivery and the post-partum period. The objective of the study was to identify provider and user perspectives regarding the knowledge of and adherence to the UCG recommendations in aspects of delivery and newborn care, both in cases of normal as well as complicated births. Methods: The study used qualitative methods with data collection from participant observations, interviews with key-informants and focus group discussions. Malterud’s Systematic Text Condensation (STC) was used for analysis. Results: The study found low knowledge about the UCG among the health workers. Various discrepancies between performed hands-on-procedures and the UCG were found related to neonatal care practices, including low use of partograms, uncertainty around timing for cord clamping, routine oronasopharyngeal suction of newborns and inadequate implementation of skin-to-skin care. Conclusions: Continued focus on systemic strategies for further implementation of the UCG is recommended.