bluuebunny/crossref_metadata_2025_split huggingface dataset:
Availability and Affordability of Children Essential Medicines in Health Facilities of Southern Nations, Nationalities, And People Region, Ethiopia: Key Determinants for Access.
Authors: Tadesse Tefera , L Habtamu Abuye , Tilahun Gizachew 
Published: December 2020

Abstract
Background: Children in resource-limited countries are more likely to die from treatable conditions than those in higher resource settings due to a lack of the right essential medicine at the right time. Globally millions of children die every year from conditions that could be treatable with existing medicines before they reach their fifth birthday. This study aimed in assessing the availability and affordability of essential medicine for children in selected health facilities of southern nations, nationalities, and peoples’ regions (SNNPR), Ethiopia. Method: A medicine outlets-based cross-sectional study was conducted to assess the availability, affordability, and prices of the 30 selected EMs for children in 30 public and 30 private medicine outlets in SNNPR from March 29 to May 5, 2019, applying WHO and Health Action International (HAI) tools. Availability was expressed as the percentage of sampled medicine outlets per sector that the surveyed medicine was found on the day of data collection. The number of daily wages required for the lowest-paid government unskilled worker (LPGW) to buy one standard treatment of an acute condition or treatment for a chronic condition for a month was used to measure affordability and median price ratio for the price of EDs. Results: Availability was varied by sectors, type of medicines, and level of health facilities. The average availability of EMs was 57.67% in the public sector and 53.67% in private sectors. Ceftriaxone, ORS, zink sulfate, and cotrimoxazole were the most widely available medicine types in both sectors. The median price ratios (MPR) for lowest-priced (LP) medicines were 1.26 and 2.24 times higher than their international reference price (IRP) in the public and private sectors respectively. Eighty-two percent of LP medicines in the public and ninety-one percent of LP medicines in the private sectors used in the treatments of prevalent common conditions in the region were unaffordable as they cost a day’s or more wages for the LPGW.Conclusion: Availability, affordability, and price are determinant pre-requisite for EMs access. According to the current work, although fair availability was achieved, the observed high price affected affordability and hence access to EMs.
Development and Validation of a Nomogram Predicting The Overall Survival for Patients With Primary Gastric Mucosa‐Associated Lymphoid Tissue Lymphoma: A SEER-Based Study
Authors: Wang Dan , Shi Ruihua , Shi Xinlin , Xu Wei 
Published: December 2020

Abstract
Purpose: To create an effective survival nomogram for patients with primary gastric mucosa‐associated lymphoid tissue (MALT) lymphoma (GML).Methods. All data of patients with primary GML from 2004 to 2015 were collected from the Surveillance, Epidemiology and End Results (SEER) database. The primary endpoint was overall survival (OS). Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves.Results. A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 months, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all p<0.05). The C-index values of the nomogram were 0.751 (95% CI: 0.729-0.773) and 0.718 (95% CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML.Conclusions. A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.
WITHDRAWN: Machine Learning Algorithms and Whole Exome Sequencing Data from Breast Cancer Patients in the UK Biobank Predict Survival
Authors: Jang Bum-Sup , Kim In Ah 
Published: December 2020

Abstract
Background: Using by machine learning algorithms, we aimed to identify the mutated gene set from the whole exome sequencing (WES) data of blood in the cancer, which is associated with overall survival in breast cancer patients.Methods: WES data from 1,181 female breast cancer patients within the UK Biobank cohort was collected. The number of mutations for each gene was summed and defined as the blood-based mutation burden per patient. Using by Long short-term memory (LSTM) machine learning algorithm and a XGBoost—a gradient-boosted tree algorithm, we developed the model to predict patient overall survival. Results: From the UK biobank-breast cancer cohort, most altered genes in blood samples were related with the TP53 pathway. In the LSTM model, the minimum 50 genes were found to predict high vs. low mutation burden. In the XGBoost survival model, the gene-set could predict overall survival showing the concordance index of 0.75 and the scaled Brier-score of 0.146 from the held-out testing set (20%, N=236). In older patients (≥ 56 years), the high mutation group based on this gene-set showed inferior overall survival compared to the low mutation group (log-rank test, P=0.042)Conclusion: The machine learning algorithms revealed the gene-signature in the UK biobank breast cancer cohort. Mutational burden observed in blood was associated with overall survival in relatively old patients. This gene-signature should be verified in prospective setting.
Antimicrobial-Resistant Pathogens in Food Handlers Serving in Mass Catering Centers
Authors: Yenew Chalachew , Tadele Fitalew 
Published: December 2020

Abstract
BackgroundThe prevalence of antimicrobial-resistant pathogens, including foodborne antibiotic-resistant bacteria, is ever increasing. An increase in antimicrobial resistance results in treatment failure and outbreaks. Mass food serving institutions are at a high risk of outbreaks due to the probability of mass infection.ObjectiveThis study aims to determine the contamination of food handlers with antibiotic-resistant bacteria and its associated factors at Debre Tabor University cafeteria.MethodsA laboratory-based cross-sectional study was conducted by following standard microbiological methods to isolate and identify foodborne bacteria from the hands of food handlers. The Kirby-Bauer disc diffusion method was used for perform the resistance profiles of the foodborne bacteria that were identified from the hands of the food in March 2020. Thirty samples each from hand and food utensil swabs were collected. Besides, work experience, drug use characteristics, and educational status of the food handler’s data were collected by using an observational checklist and interview questions. Descriptive statistics, correlation, and linear regressions were used to analyze the data.ResultsThe result shows the contamination of food handlers with varying pathogenic microbial organisms. The food handlers were mostly contaminated with multiple antibiotics-resistance (MAR) of Escherichia coli 43% (95% CI: 41.2%, 46.9%), Salmonella 36.7% (95% CI:33.2%, 38.7%), and Shigella 20% (95% CI: 19.2%, 26.9%). The study identifies poor personnel hygiene, lack of food safety training, and lack of sufficient food safety knowledge of the food handlers.Conclusions﻿The contamination of food handlers with antimicrobial-resistant microbes at the university cafeteria could indicate the likelihood of the occurrence of foodborne outbreaks. Hence, continuous awareness creation and strict supervision were preventing the contamination of the food and related consequences.
Molecular Typing and Phenotypic and Genotypic Evaluation of Antibiotic Resistance and Virulence Factors of the Methicillin-Resistant Staphylococcus Aureus Bacteria Isolated From Vegetable and Salad Samples
Authors: Tavakoli-Far Bahareh , Mousavi Bita , Mashak Zohreh , Rezaei Mohammad Adel , Doregiraee Fatemeh , Kachoie Mehrdad Ataie , Shahraki Manouchehr Momeni , Dehkordi Farhad Safarpoor , Ranjbar Reza , Rahimi Ebrahim , Jafari-Eskari Sedighe 
Published: December 2020

Abstract
BackgroundMethicillin-resistant Staphylococcus aureus is an important cause of foodborne diseases. The present research evaluated the antibiotic resistance properties, distribution of virulence factors, and molecular typing of MRSA bacteria isolated from vegetable and salad samples. MethodsThree-hundred and fifty vegetable and salad samples were examined for the presence of S. aureus using the culture. MRSA bacteria were identified using cefoxitin and oxacillin disk diffusion. The phenotypic pattern of antibiotic resistance was assessed by disk diffusion. ResultsThe PCR evaluated the distribution of antibiotic resistance and virulence genes. Forty-five out of 350 (12.85%) vegetable and salad samples were positive for S. aureus. Twenty-six isolates out of 45 (57.77%) S. aureus bacteria were determined as MRSA. MRSA bacteria harbored the uppermost prevalence of resistance against cefoxitin (100%), ceftaroline (100%), penicillin (100%), tetracycline (88.46%), gentamicin (80.76%), trimethoprim-sulfamethoxazole (69.23%), and erythromycin (69.23%). The prevalence of MRSA bacteria resistance recovered from vegetable and salad samples against more than seven antibiotic agents was 12.50% and 27.77%, respectively. BlaCTX-M (100%), blaZ (100%), aacA-D (61.53%), tetK (57.69%), dfrA1 (46.15%), and vanA (42.30%) were the most commonly detected antibiotic resistance genes. PVL (57.69%), coa (53.84%), and hla (38.46%) were the most commonly detected virulence factors amongst the MRSA bacteria. ConclusionMRSA isolates had a similarity lower than 80%, categorized in the same group. The presence of one or more virulence factors and antibiotic resistance genes amongst the resistant-MRSA bacteria signifies an important threat rendering the consumption of contaminated vegetables and salads.
Are Global Experiences During Medical School Associated with Future Medical Practice? A Cross-Sectional Analysis of Survey and Medical School Application Data
Authors: Slifko Shay E , Vielot Nadja A. , Becker-Dreps Sylvia , Pathman Donald E. , Myers Justin G. , Carlough Martha C. 
Published: December 2020

Abstract
Background: Global health interest has grown among medical students over the past twenty years. Most medical schools offer global health opportunities. Studies suggest completing global health electives during medical school may increase likelihood of choosing a primary care discipline or working with underserved populations, yet they have generally not considered students’ interests and experiences prior to medical school. This study aimed to assess the associations of pre-medical school factors and global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.) and whether respondents reported perceived benefits from global electives. Methods: We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students’ backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S.Results: Of 161 respondents, five to eight years post-graduation, 78% reported work, research, or teaching with a focus on global or underserved U.S. populations. Completing a global health elective during medical school (p=0.0002) or during residency (p=0.01) were positively associated with currently working with underserved populations, and pre-medical school experiences were not associated (p=0.1). Adjusting for race and ethnicity, completing a global health elective during medical school was associated with a 38% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings. Conclusion: Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations in the U.S. They reported the experience improved their cultural competency and public health skills. These data can be used to design medical school curricula that encourage global health electives, and support skills that will benefit future work with underserved populations, either in the U.S. or abroad.
Changes in Macrophageand Inflammatory Cytokine Expressions During Fracture Healing in an Ovariectomized Mice Model
Authors: Chen Lin , Cheng Shao , Sun Kanghui , Wang Jing , Liu Xinhua , Zhao Yongjian , Yang Junjie , Zhao Dongfeng , Xue Chunchun , Tao Yuren , Zhao Shitian , Zhang Hao , Lu Sheng , Shi Qi , Wang Yongjun , Shu Bing 
Published: December 2020

Abstract
Background: Macrophages and inflammatory cytokines plays important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis has not been fully revealed.Methods:Tibia transversefracture was established 12 weeks after ovariectomyor shamoperation in 3-month old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatorymacrophages, ostealmacrophages and gene expressions of tumor necrosis factor-α,interleukin-6, interleukin-1βand macrophage conversion related molecules in the fracturehaematoma or callus were also detected.Results:The process of fracture healing,especially the phases of endochondral ossification and callus remodeling, was delayed in ovariectomized mice.The expressions of tumor necrosis factor-α andinterleukin-6, but not interleukin-1β, in the fracturehaematoma or callus were disturbed. We also foundthe decreases in M1 and M2 macrophages inthe initialinflammatory stage, M2 macrophagesin the middle stage and ostealmacrophagesin the middle and late stages of fracture healing in ovariectomized mice.Conclusions: The expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.
Associations of Individual and Joint Expressions of ERCC6 and ERCC8 with Clinicopathological Parameters and Prognosis of Gastric Cancer
Authors: Chen Jing , Li Liang , Sun Li-Ping , Yuan Yuan , Jing Jing-jing 
Published: December 2020

Abstract
BackgroundExcision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic disease and cancer. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.MethodsIn this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) with 109 paired GC and para-cancerous normal tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis for the exploration of the function and regulation network of ERCC6 and ERCC8 in GC.ResultsIndividual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. Protein expressed levels of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated an increased OS with higher ERCC6 protein expression and ERCC8 mRNA expression, and a decreased OS with double negative ERCC6-ERCC8 expression. Bioinformatic analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. Direct physical interactions were found between ERCC6 and ERCC8.ConclusionsIndividual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Expressed levels of ERCC6 and double negative ERCC6-ERCC8 protein, and ERCC8 mRNA were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and could regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.
Network Pharmacology-based Systematic Analysis of Molecular Mechanisms of Dingji Fumai Decoction for Ventricular Arrhythmia
Authors: Liang Yi , Liang Bo , Wu Rui Xin , Chen Wen , ZHAO Li-zhi 
Published: December 2020

Abstract
Background: Dingji Fumai decoction (DFD), a traditional herbal mixture, has been widely used to ventricular arrhythmia (VA) in clinical practice in China. However, research on the bioactive components and underlying mechanisms of DFD in VA is still scarce. Methods: Components of DFD were collected from TCMSP, ETCM, and literature. Then, the chemical structures of each component were obtained from PubChem. Next, SwissADME and SwissTargetPrediction were applied for compounds screening and targets prediction of DFD, meanwhile, targets of VA were collected from DrugBank and OMIM. Then, the H-C-T-D network as well as the PPI network were constructed based on the data obtained above. CytoNCA was utilized to filter hub genes and VarElect was used to analyze the relationship between genes and diseases. At last, Metascape was employed for systematic analysis on the potential targets of herbals against VA, and AutoDock was applied for molecular docking to verify the results.Results: A total of 434 components were collected, 168 of which were qualified, and there were 28 shared targets between DFD and VA. Three function modules of DFD were found from the PPI network. Further systematic analysis of shared genes and function modules explained the potential mechanism of DFD in the treatment of VA, molecular docking has verified the interactions. Conclusions: DFD could be employed for VA through mechanisms, including complex interactions between related components and targets, as predicted by network pharmacology and molecular docking. This work confirmed DFD could apply for the treatment of VA and promoted the explaining of DFD for VA in the molecular mechanisms.
CXCR4 Blockade Enhances The Sensitivity Of Osteosarcoma To Doxorubicin By Inducing Autophagic Cell Death Via PI3K-Akt-Mtor Pathway Inhibition
Authors: Liao Yu-Xin , Yu Hai-Yang , Lv Ji-Yang , Zhou Zi-Fei , Xu Tian-Yang , Yang Dong , Gao Qiu-Ming , Fan Lin , Liu Kaiyuan , Li Guo-Dong 
Published: December 2020

Abstract
Background: Doxorubicin is one of the most frequent used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to its treatment failure. CXCR4 has been proved to regulate osteosarcoma progression and metastasis, however whether CXCR4 is also implicated in OS chemoresistance and its molecular mechanisms have not yet been fully elucidated. In this study, we investigated CXCR4-mediated autophagy for OS chemotherapy. Methods: Cell viability, western blot and apoptosis were performed to evaluate doxorubicin resistance after CXCR4 regulation (downregulation or upregulation) and treatment with autophagy modulators (bafilomycin A1 or rapamycin) in two OS cell lines (LM8 and Dunn). Autophagy-related proteins (Beclin1 and LC3B) detected by western blot, autophagosomes and autolysosomes observed by transmission electron microscopy, and autophagic flux monitored by confocal microscopy were utilized to comprehensively assess autophagy level changes. A C3H mouse osteosarcoma orthotopic model was established to determine anti-tumor effect of CXCR4 antagonist AMD3100 and doxorubicin in vivo.Results: CXCR4 inhibition enhanced doxorubicin-induced apoptosis by reducing p-glycoprotein, while CXCR4 overexpression promoted OS doxorubicin resistance. Moreover, CXCR4 inhibition combined with or without doxorubicin increased Beclin1 and LC3B expression, numbers of autophagosome and autolysosome, and induced autophagic flux activation by suppressing PI3K-Akt-mTOR pathway. In addition, pretreatment with autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogation-induced cell death. Finally, CXCR4 antagonist AMD3100 synergistically reinforced anti-tumor effect of doxorubicin in orthotopic OS mouse model. Conclusions: This study revealed CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Targeting CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.
The Mechanism of Sesame Resistance Against Macrophomina Phaseolina Was Revealed via Comparison of Transcriptomes of Resistant and Susceptible Sesame Genotypes
Authors: Yan Wenqing , Ni Yunxia , Liu Xintao , Zhao Hui , Chen Yanhua , Jia Min , Liu Mingming , Liu Hongyan , Tian Baoming 
Published: December 2020

Abstract
Background: Sesame (sesamum indicum) charcoal rot, a destructive fungal disease caused by Macrophomina phaseolina (Tassi) Goid (MP), is a great threat to the yield and quality of sesame. However, there is a lack of information revealing gene-for-gene relationship between sesame and MP, and the molecular mechanism in the interaction is not yet clear. The aim of this study is to interpret the molecular mechanism of sesame resistance against MP in disease-resistant (DR) and disease-susceptible (DS) genotypes based on transcriptomes, which is the first report on the interaction between sesame and MP from the transcriptomes.Results: A set of core genes that function in sesame disease resistance were revealed in our investigation by comparative transcriptomics, which preferentially associate with GO terms such as ribosome-related processes, fruit ripening, regulation of jasmonic acid mediated signaling pathway and cell-cell signaling. In addition, 52 potential resistance-related genes differentially and persistently expressed all through were obtained in sesame. Furthermore, we preliminarily studied the immune response mechanism of sesame against MP and found that auxin signal pathway shows negative regulation in the process. Also, the most highlighted pathway JA/ET signal transduction plays a negative regulatory role in sesame resistance against MP. Finally, a JAZ gene (LOC105168467) and an ERF transcription factor (LOC105171710) that may be related to disease resistance were screened. Conclusions: In our investigation, the mechanism of resistance against MP from the transcriptomes were illustrated, which is a complex bioprocess involved in many phytohormones and disease resistance-related genes. The findings not only shed more light on mechanism of interaction between sesame and MP, but also help us identify key genes and transcription factors (TFs) associated with charcoal rot resistance in sesame.