bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Urban Family Physician Program on health indicators in Iran: an Interrupted Time Series Analysis
Authors: Hajibadali Parisa , Hashemiparast Minasadat , Iraji Zeinab , Lotfalinejad Elham , Allahverdipour Hamid , Nadrian Haidar 
Published: July 2020

Abstract
BackgroundIn 2015, the Iranian Urban Family Physician Program (UFPP) was implemented in urban health centers. In the present study, we aimed to evaluate the trend of health indicators across a ten-year period in an Iranian population and to measure the possible effects of this intervention on health indicators.MethodsAn interrupted time series analysis (ITSA) was performed on a ten-years (from 2009 to 2018) of annual data set covering all healthcare indicators associated to the UFPP in Bonab County, Iran. The time of intervention was at the 7th data point in 2015. Health indicators were divided into two groups including process indicators (Modern Contraceptives Use (MCU), Prenatal and Postpartum care visits, Clinical Breast Examinations (CBE), brucellosis and tuberculosis (TB) incidence), and outcome indicators (Total fertility rate (TFR), Maternal Mortality Rate (MMR), Stillbirth Rate (SBR), Infant mortality Rate (IMR), Neonatal Mortality Rate (NMR), 1–59 months old Mortality Rate, Low Birth Weight (LBW), crud birth rate (CBR) and the rates of Infants fed by Formula milk.ResultsThe ratio of some process indicators, including the MCU (b = -5.13. 95% Confidence Interval (CI): -8.01 to -2.26), incidence of tuberculosis (b = .016. 95% CI: -1.01 to 1.34) and brucellosis (b = 3.04. 95% CI: -3.4 to 9.50) had a decreasing trend from 2008 to 2018. However, the CBE (b = 0.60. 95% CI: -4.97 to 6.18), prenatal care visits, (b= -4.25. 95% CI: -10.4 to 1.5) postpartum care visits (b = -22.83. 95% CI: -31.44 to -14.21), and first time care visits during pregnancy (b = -5.59. 95% CI: -14.52 to 3.32) were found with increasing trends. In contrast, the rate of at least six-time care visits during pregnancy was found to be in a decreasing trend (b = -10.32. 95% CI: -16.82 to -3.82). A series of outcome indicators including MMR (b = 24.78. 95% CI: 2.88 to 46.61), TFR (b = 0.07. 95% CI: 0.01 to 0.13), 1–59 Month old Mortality Rate (b = − .16. 95% CI: − .45 to .12), LBW (b = .33. 95% CI: − .08 to .40), Formula-fed infant rate (b = .48. 95% CI: − .007 to .97), Delivery rate in high-risk groups (b = 1.85. 95% CI: 1.22 to 2.49) and CS (b = -3.43. 95% CI: -5.73 to -1.12) had increasing trends from 2008 to 2018. In contrast, SBR (b = − .04. 95% CI: − .21 to .12), NMR (b = − .77. 95% CI: -2.91 to 1.36), IMR (b = -1.05. 95% CI: -2.99 to .89) and CBR (b = − .97. 95% CI: -1.85 to − .09) were in decreasing trends.ConclusionThe UFPP was found with positive impacts on some process, proximal and distal outcome indicators, but its positive impacts on the trends of some critical indicators, including MMR, NMR and IMR remained questionable. Our findings may shed light on the role of some other factors like social determinants of health in the programs like the UFPP.
A Novel Biomarker TLCD1 Correlates with Prognosis and Immune Infiltrates in Hepatocellular Carcinoma
Authors: Shen Hanyu , Huang Ailong , Zhu Dandan , Zhang Jiali , Ren Shiqi , Duan Lian , Sun Pingping , Wang Ziheng , Duan Yinong 
Published: July 2020

Abstract
Background: The HCC has seen a spike in the morbidity and the mortality rate in recent times. This calls for an urgent understanding of the underlying molecular mechanisms of the HCC and to speed up the quest for the search of the target molecules to ensure quick diagnosis and prognosis subsequently. TLCD1 is a gene only reported in membrane fluidity. The variations in the TLCD1 expression levels related to the infiltration of the immune cells in HCC and the prognosis shall be examined initially.Methods: The data received from TCGA shall provide the details of the gene expression, clinicopathology analysis and TME estimate, along with the enrichment analysis. Moreover, we performed additional analysis of the bioinformatics available. The immune responses of TLCD1 expression in HCC were analyzed using CIBERSORT and TIMER, while the statistical analysis was handled through R. HPA was used to validate the outcomes.Results: Higher TLCD1 expression is strongly correlated with a poor prognostic and worse overall survival. Specifically, the increase in TLCD1 expression positively correlated with Tregs cells and T cells CD4 memory resting. The pathways strongly associated with TLCD1 was fatty acid metabolism and PPAR signaling pathway.Conclusions: From the outcome of the study, it could be surmised that TLCD1 could be considered as a potential target for future treatment of HCC, as it was observed to be associated with the tumor-infiltrating immune cells in tumor microenvironment, establishing itself as a novel potential prognostic biomarker in HCC.
What is the Impact of the COVID-19 Pandemic on Emergency Medicine Residency Training: An Observation Study
Authors: Lo Hsiang-Yun , Lin Shen-Che , Chaou Chung-Hsien , Chang Yu-Che , Ng Chip-Jin , Chen Shou-Yen 
Published: July 2020

Abstract
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has engendered difficulties for health systems globally; however, the effect of the pandemic on emergency medicine (EM) residency training programs is unknown. The pandemic has engendered reduced volumes of emergency department (ED) patients, except for those with COVID-19 infections, and this may reduce the case exposure of EM residents. The primary objective of this study was to compare the clinical exposure of EM residents between the prepandemic and pandemic periods. MethodsThis was a retrospective study of EM resident physicians in Taiwan. We performed a medical record review and retrieved data regarding patients seen by EM residents in the ED between September 1, 2019, and April 30, 2020. The number and characteristics of patients seen by residents were recorded, and the training schedules, including clinical working hours, of EM residents were determined. We compared the data between the prepandemic and pandemic periods.ResultsA total of 51,337 patients were managed by 36 EM residents during the 8-month study period. The mean number of patients per hour (PPH) seen by EM residents decreased significantly during the pandemic period. The PPH seen by residents in the adult ED decreased in all three hospitals during the pandemic. The average number of patients managed by residents decreased by 50% and 70% in the trauma ED and pediatric ED during the pandemic, respectively. The severity of patient illness did not change significantly between the periods. ConclusionsThe COVID-19 pandemic engendered a reduced ED volume and decreased EM residents’ clinical exposure. All portion of EM residency training were affected by the pandemic, with pediatric EM being the most affected. The patient volume reduction may persist and in turn reduce patients’ case exposure until the pandemic subsides. Adjustment of the training programs may be necessary and ancillary methods of learning should be used to ensure adequate EM residency training.
Engineering cofactor metabolism for improved protein and glucoamylase production in Aspergillus niger
Authors: Sui Yu-fei , Schütze Tabea , Ouyang Li-Ming , Lu Hong-zhong , Liu Peng , Xiao Xian-zun , Qi Jie , Zhuang Yingping , Meyer Vera 
Published: July 2020

Abstract
Background: Nicotinamide adenine dinucleotide phosphate (NADPH) is an important cofactor ensuring intracellular redox balance, anabolism and cell growth in all living systems. Our recent multi-omics analyses of glucoamylase (GlaA) biosynthesis in the filamentous fungal cell factory Aspergillus niger indicated that low availability of NADPH might be a limiting factor for GlaA overproduction. Results: We thus employed the Design-Build-Test-Learn cycle for metabolic engineering to identify and prioritize effective cofactor engineering strategies for GlaA overproduction. Based on available metabolomics and 13C metabolic flux analysis data, we individually overexpressed seven predicted genes encoding NADPH regeneration enzymes under the control of Tet-on gene switch in two A. niger recipient strains, one carrying a single and one carrying seven glaA gene copies, respectively, to test their individual effects on GlaA overproduction. Both strains were selected to understand if a strong pull towards glaA biosynthesis (seven gene copies) mandates a higher NADPH supply compared to the native condition (one gene copy). Detailed analysis of all 14 strains cultivated in shake flask cultures uncovered that overexpression of the gsdA gene (glucose 6-phosphate dehydrogenase), gndA gene (6-phosphogluconate dehydrogenase) and maeA gene (NADP-dependent malic enzyme) supported GlaA production on a subtle (10%) but significant level in the background strain carrying seven glaA gene copies. We thus performed maltose-limited chemostat cultures combining metabolome analysis for these three isolates to characterize metabolic-level fluctuations caused by cofactor engineering. In these cultures, overexpression of either the gndA or maeA gene increased the intracellular NADPH pool by 45% and 66%, and the yield of GlaA by 65% and 30%, respectively. In contrast, overexpression of the gsdA gene had a negative effect on both total protein and glucoamylase production. Conclusions: This data suggests for the first time that increased NADPH availability can indeed underpin protein and especially GlaA production in strains where a strong pull towards GlaA biosynthesis exists. This data also indicates that the highest impact on GlaA production can be engineered on a genetic level by increasing the flux through the reverse TCA cycle ( maeA gene) followed by engineering the flux through the pentose phosphate pathway ( gndA gene). We thus propose that NADPH cofactor engineering is indeed a valid strategy for metabolic engineering of A. niger to improve GlaA production, a strategy which is certainly also applicable to the rational design of other microbial cell factories.
MiR-24-3p and various cancers: From a meta-analysis view
Authors: Wang He , Chen Chunyang , Zhang Weijie , Ding Keke , Hou Jianquan 
Published: July 2020

Abstract
Background: A growing number of researches suggests that microRNAs (miRNAs) as oncogene or tumor suppressor genes play a fundamental role in various kinds of cancers. Among them, miR-24-3p, as a star molecule, is widely studied. However, the prognostic value of miR-24-3p is unclear and controversial. We conducted this meta-analysis to evaluate the prognostic value of miR-24-3p in a variety of cancers by integrated existing articles from four databasesMethods: PubMed, Embase, Web of Science, and Cochrane Library (last update in March 2020) were searched for approach literature. Hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the association between miR-24-3p expression levels and prognostic value or clinicopathological characteristics, respectively.Results: A total of 15 studies from 14 literature were finally qualified and concluded in the present meta-analysis. A significantly worse overall survival was observed in higher expression of miR-24-3p cancer group for OS(Overall survival) of log rank tests and cox multivariate regression by fixed effects model. Also, we found a significant correlation between elevated miR-24-3p levels to RFS (Recurrence-free survival) and DFS(Disease free survival). In addition, the pooled odds ratios (ORs) showed that evaluated miR-24-3p was also associated with the larger tumor size (≥5cm) and advanced TNM stage (Ⅲ and Ⅳ).Conclusion: Built on the above findings, elevated expression levels of miR-24-3p may serve as a promising biomarker used to predict the worse prognosis of cancer patients.
The Diagnostic Value of LGALS1 in Esophageal Cancer and its Potential Molecular Pathways via Bioinformatic Analysis
Authors: Li Dan , Yang Heng , Lei Yue , Guo Qiang , Ji Yanmei , Guo Jialong 
Published: July 2020

Abstract
Background: Esophageal cancer is one of the most common malignant tumors. The purpose of this study was to reveal the expression of LGALS1 in esophagus cancer (ESCA) and its clinical value, and to explore the mechanism of LGALS1 in the occurrence and development of ESCA.Methods: Oncomine, Tumor Immune Estimation Resource (Timer) and The Cancer Genome Atlas (TCGA) database were used to analyze the expression of LGALS1 in ESCA and its value in the diagnosis of ESCA. The correlation between LGALS1 and the clinicopathological characteristics of ESCA patients was analyzed in the Ualcan database. In TCGA database, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to elucidate the potential mechanism underlying the role of LGALS1 in ESAC. LGALS1 co-expressed genes were imported into the String database to build a protein-protein interaction (PPI) network. The CytoHubba plug-in in Cytoscape was used to screen the hub gene and was verified in Gene Expression Profiling Interactive Analysis (GEPIA) and TCGA database.Results: LGALS1 was highly expressed in ESCA tissues. Increasing the expression level of LGALS1 was related to age, ethnicity, clinical stage, tumor grade, and histological subtype of ESCA patients, and receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.8511 (P <0.001). There are 482 LGALS1 co-expressed genes. GO and KEGG show that LGALS1 co-expressed genes are mainly involved in endothelial cell differentiation, transforming growth factor receptor signaling pathway, epithelial cell proliferation, ECM receptor interactions, leukocyte migration, transcriptional disorders during cancer, PI3K/AKT signaling pathway and other processes. GSEA showed that elevated LGALS1 was mainly enriched for ECM receptor interactions, cancer pathways, and TGF BETA signaling pathways. The Hub genes COL1A1, FN1, COL1A2, COL3A1, COL5A1, COL5A2, COL4A2, COL18A1, and COL6A1 are higher expressed in ESCA tissues and have diagnostic significance in ESCA.Conclusion: LGALS1 expression is elevated in ESCA patients and may be a potential diagnostic marker for ESCA patients. PI3K/AKT signaling pathway, TGF BETA signaling pathway, cancer pathway, cytokine and cytokine interaction may be an important pathway for regulation in occurrence and development of ESCA.
A 4-gene Signature Predicts Prognosis of Uterine Serous Carcinoma
Authors: Chen Hui , Li Lingjun , Qin Ping , Xiong Hanzhen , Chen Ruichao , Zhang Minfen , Jiang Qingping 
Published: July 2020

Abstract
Background: Uterine serous carcinoma (USC) is a rare, aggressive variant of endometrial cancer that accounts for more than 50% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods: USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results: We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4‐gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions: Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.
Understanding COVID-19 nonlinear multi-scale dynamic spreading in Italy
Authors: Quaranta Giuseppe , Formica Giovanni , Machado J. Terneiro , Lacarbonara Walter , Masri Sami F. 
Published: July 2020

Abstract
The outbreak of COVID-19 in Italy took place in Lombardia, a densely populated and highly industrialized northern region, and spread across the northern and central part of Italy according to quite different temporal and spatial patterns. In this work, a multi-scale territorial analysis of the pandemic is carried out using various models and data-driven approaches. Specifically, a logistic regression is employed to capture the evolution of the total positive cases in each region and throughout Italy, and an enhanced version of an SIR-type model is tuned to fit the different territorial epidemic dynamics via a differential evolution algorithm. Hierarchical clustering and multidimensional analysis are further exploited to reveal the similarities/dissimilaritiesof the remarkably different geographical epidemic developments. The combination of parametric identifications and multi-scale data-driven analyses paves the way towards a closer understanding of the nonlinear, spatially nonuniform epidemic spreading in Italy.
Living with cancer in the COVID-19 pandemic: An Italian survey on self-isolation at home
Authors: Biagioli Valentina , Albanesi Beatrice , Belloni Silvia , Piredda Alessio , Caruso Rosario 
Published: July 2020

Abstract
Objective: To investigate the perception of self-isolation at home in patients with cancer during the lockdown period because of the COVID-19 outbreak in Italy.Methods: A cross-sectional descriptive study was conducted through an online survey from March 29th to May 3rd, 2020. Perception of self-isolation was assessed in patients with cancer during quarantine at home using the ISOLA scale, after evaluation of its psychometric properties. Content analysis was used to analyse two open-ended questions.Results: Participants were 195 adult patients with cancer (female = 76%; mean age = 50.3 ± 11.2; haematological malignancy = 51.3%). They reported moderate isolation-related suffering (M = 2.64 ± 0.81), problems in the relationship with others (M = 3.31 ± 1.13), and difficulties in the relationship with oneself (M = 3.14 ± 1.06). Patients who experienced significantly more social problems were the older ones, with lower education, and living without minor children. Overall, four main categories emerged from the qualitative content analysis: 1) Lack of freedom and social life, 2) Uncertainty and worries, 3) Feeling supported, and 4) Dealing with isolation.Conclusion: Living with cancer in the COVID-19 pandemic was often perceived as an isolating experience, primarily in terms of detachment from loved ones.
In-hospital mortality from Coronavirus Disease 2019 in a northern Italian centre:results of a competing risk analysis from SMAtteo COvid19 REgistry (SMACORE)
Authors: Zuccaro Valentina , Celsa Ciro , Sambo Margherita , Battaglia Salvatore , Sacchi Paolo , Biscarini Simona , Valsecchi Pietro , Pieri Teresa Chiara , Gallazzi Ilaria , Colaneri Marta , Sachs Michele , Roda Silvia , Asperges Erika , Lupi Matteo , Filippo Alessandro Di , Seminari Elena , Matteo Angela Di , Novati Stefano , Maiocchi Laura , Enea Marco , Attanasio Massimo , Cammà Calogero , Bruno Raffaele 
Published: July 2020

Abstract
Objectives An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. MethodsAll consecutive hospitalised patients from February 21stto March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge.Results 426 adult patients (median age 68 (IQR, 56 to 77 years) were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4thwere independent risk factors associated with in-hospital mortality.Conclusions Olderage, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19
Interferon regulatory factor 8 induces alveolar macrophage hypoxia/reoxygenation injury via the PINK1/Parkin mitophagy pathway
Authors: Zhang Lin , Hao Bo , He Ruyuan , Lu Zilong , Feng Haojie , Shen Xiaokang , Zhang Ziyao , Jiang Wenyang , Wang Wei , Fan Tao , Geng Qing 
Published: July 2020

Abstract
Background: Lung ischemia-reperfusion injury (LIRI) is a complex process and macrophages play a central role in it. Interferon regulatory factor 8 (IRF8) is a transcription factor in the innate immune system, which, together with autophagy, are important components of the mechanisms of LIRI. We aimed to explore the regulatory role of IRF8 in hypoxia/reoxygenation (HR) injury and PINK1-mediated mitophagy.Methods: Cultured NR8383 macrophages were subjected to HR as an in vitro model of LIRI. Cell viability, cell damage and inflammation during HR were evaluated by Cell Counting Kit-8 assay, lactate dehydrogenase assessment and enzyme linked immunosorbent assay, respectively. Meanwhile, PINK1/Parkin-mediated mitochondrial autophagy was detected by quantitative real-time PCR, western blot, transmission electron microscopy and double immunofluorescence labeling method. The effects of IRF8 and PINK1 on cell injury, inflammatory response and autophagy during HR were assessed using IRF8 short-hairpin RNA plasmids and PINK1 overexpression plasmids , respectively. Results: IRF8 inhibition was able to alleviate cell injury, inflammatory response and autophagy while PINK1 overexpression could exacerbate them. Moreover, IRF8 downregulation could reduce the expression of PINK1 in HR injury and attenuate the effects of it. Conclusion: IRF8 was able to induce HR injury via the PINK1/Parkin mitophagy pathway. Inhibition of IRF8 and PINK1/Parkin-mediated mitophagy might be a potential target for the treatment of LIRI.