bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Hidden Patterns of Fatal Pedestrian Traffic Accidents in East Azerbaijan Province of Iran: Application of Categorical Principal Component&nbsp;Analysis (CATPCA)
Authors: Jamali-Dolatabad Milad , Sarbakhsh Parvin , Sadeghi-bazargani Homayoun 
Published: December 2020

Abstract
Background: Identifying patterns and hidden relationships among fatal pedestrian road traffic accident (FPRTA) features can be effective to reduce pedestrian fatalities. This study aimed to detect the patterns of FPRTA in the East Azerbaijan province of Iran.Methods: The present study is a descriptive-analytic study based on the data of all 1782 FPRTAs that occurred in East Azerbaijan province of Iran during the years 2010 to 2019 collected by the forensic organization. CATPCA (Categorical Principal Component Analysis) was performed to recognize hidden patterns in the data by extracting principal components from the set of 13 features of FPRTA. The importance of each component was assessed by using the variance accounted for (VAF) index. Results: The optimum number of components to fit the CATPCA model was six with a 71.09% explanation of the total variation. The first and most important component with VAF=22.04% contained the demographic and socioeconomic characteristics of the pedestrians. The second-ranked component with VAF=12.96% was about the injury. The third component with VAF=10.56% was about the severity of the accident. The fourth component with VAF=9.07% was somehow related to the knowledge and observance of the traffic rules. The fifth component with VAF=8.63% was about the quality of medical relief and finally, the sixth component with VAF=7.82% was about environmental conditions. Conclusion: CATPCA revealed hidden patterns of FPRTA data in the format of six components. The revealed patterns showed that some interactions between correlated features led to a higher mortality rate.
Proteomics and Metabonomics Analyses of Covid-19 Complications in Patients With Pulmonary Fibrosis
Authors: Yang Jianrong , Chen Chunxia , Chen Wan , Huang Luying , Fu Zhao , Ye Kun , Lv Liwen , Nong Zhihuang , Zhou Xing , Lu Wensheng , Zhong Mei 
Published: December 2020

Abstract
Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.
A Global Genome-wide Scan With Optimal Cutoff Mining for Emerging Biomarkers in Head and Neck Squamous Cell Carcinoma
Authors: Chi Li-Hsing , Wu Alexander TH , Hsiao Michael , Li Yu-Chuan (Jack) 
Published: December 2020

Abstract
Background: The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). In order to utilize a continuous gene expression for survival analysis, it is necessary to determine a cutoff point by the dichotomization of the patients. There is some optimization software for cutoff determination. However, those predetermined cutoffs by software usually set at the median, 1/4 quantile, or 3/4 quantile of RNA sequencing (RNA -Seq) value to nd a significant P-value of the Kaplan-Meier curve. There are few clinicopathological features available on their pre-processed data sets.Methods: We developed a comprehensive work flow by R script, running on the Rstudio platform. It includes data retrieving and pre-processing, feature selection, cutoff mining engine, Kaplan-Meier survival analysis, Cox proportional hazard modeling, and biomarker discovery.Results: Using this work flow on the TCGA HNSCC cohort, we scanned human protein-coding genes (20,500) programmatically. After adjustment with other confounders, we found that the clinical tumor stage and the surgical margin involvement are independent risk factors in patient survival. According to the resulting tables with Bonferroni adjusted P-value under optimal cutoff as well as hazard ratio (>= 1:5), there were ten candidate biomarkers, named as DKK1, CAMK2N1, STC2, PGK1, SURF4, USP10, NDFIP1, FOXA2, STIP1, and DKC1, which are significantly associated with the poor prognosis of overall survival (OS). At the same time, the other ten genes were over-expressed in the better survival patients (with hazard ratio <= 0:5), named as ZNF557, ZNF266, IL19, MYO1H, FCGBP, LOC148709, EVPLL, PNMA5, IQCN (previous name as KIAA1683), and NPB. Further validations are warranted.Conclusions: We suggested this analysis tool equipped with an optimal cutoff finder will help with biomarker discovery of protein-coding genes, in terms of tumor-agnostic therapy.
Multi - Bacillary Leprosy Under Chinese&nbsp;Leprosy Elimination Program
Authors: Zhang Qingping , Ge Li , Zhang Hong , Chen Ping , Lin Zhaoxing , Wang Yaofei , Yang Xiaodong 
Published: December 2020

Abstract
Background: Objectives: To analyze the sociodemographic and clinical factors associated with multi-bacillary(MB) leprosy in elimination planning areas in Northwest China.Design: Retrospective observational study.Setting: Three specialized hospitals were included.Participants : The medical records of leprosy in Shaanxi Province from 2004 to 2020 were collected from the leprosy management information system (LEPMIS).Primary and secondary outcome measures: The basic situation of leprosy treatment and follow-up were investigated.Results : 305 new cases of leprosy were included in the study. 272 cases (89.18%) were MB leprosy, and 33 (10.82%) were pauci-bacillary (PB) leprosy. Male patients were more likely to have neurological injury ( P <0.001; OR:0.35; 95%CI:0.194-0.630). Patients over 60 years old were more likely to have leprosy deformity ( P <0.001; OR:0.113; 95%CI:0.027-0.478) and nerve injury ( P =0.035; OR:0.333; 95%CI:0.115-0.965). Patients with marriage histories were more likely to have leprosy deformities ( P =0.018; OR:0.842; 95%CI: 0.718-0.987). Patients with passive detection had a lower probability of leprosy reaction ( P =0.011; OR:4.268; 95%CI:1.276-14.272); Patients with nerve damage, positive skin smear test or level I or level II disability were more likely to be classified as MB leprosy.Conclusions : MB leprosy is related to social and demographic factors (with or without marriage history, age at diagnosis, discovery mode) and clinical factors (such as the number of skin lesions and nerve lesions).
Effect of Hypoglycemia on Measures of Myocardial Blood Flow and Myocardial Injury in Adults With and Without Type 1 Diabetes: A Prospective, Randomized, Open-Label, Blinded Endpoint, Cross-Over Study
Authors: Noh Radzi M , Graveling Alex J , Lang Ninian N , White AC , Lee Kuan Ken , Mills Nicholas L , Newby David E , Lang Chim C , Frier Brian M 
Published: December 2020

Abstract
Aims: Hypoglycemia provokes a profound autonomic response in humans including cardiovascular effects. This study examined the effect of experimentally-induced hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.Methods and Results: In a prospective, randomized, open-label, blinded, endpoint cross-over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non-diabetic volunteers, underwent hyperinsulinemic euglycemic (blood glucose 4.5-5.5 mmol/L) and hypoglycemic (2.2-2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high-sensitivity cardiac troponin I (hs-cTnI) concentration. During euglycemia, a non-significant trend for lower CFR was observed in participants with type 1 diabetes than in those without type 1 diabetes (3.66±0.47 versus 3.92±0.85), and a non-significant lower trend also occurred during hypoglycemia (type 1 diabetes: 3.54±0.58 versus non-diabetes: 3.80±0.84). A generalized linear mixed-model analysis was performed, with diabetes status and euglycemia or hypoglycemia as factors affecting CFR. No significant statistical difference in CFR was observed for diabetes status (p=0.23) or between euglycemia and hypoglycemia (p=0.31). No changes in hs-cTnI occurred during hypoglycemia or in the recovery period (p=0.86).Conclusions: While the observed reduction in coronary flow reserve did not achieve significance during exposure to insulin-induced hypoglycemia in healthy young men with type 1 diabetes, with no evidence of myocardial injury, adverse cardiovascular effects of hypoglycemia cannot be excluded in older people who have coronary disease. Further studies are required to investigate this putative problem.
HIV Prevention at Drug Shops: Awareness and Attitudes among Shop Dispensers and Young women about Oral Pre-exposure Prophylaxis and the Dapivirine Ring in Shinyanga, Tanzania
Authors: Tubert Julia , Packel Laura , Hunter Lauren A. , Mfaume Rashid , Njau Prosper , Ramadhani Angela A. , Liu Jenny X. , McCoy Sandra I. 
Published: December 2020

Abstract
Background: HIV risk remains high among adolescent girls and young women (AGYW, ages 15-24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring. Methods: In July-August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create “girl-friendly” drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3-5 months, we surveyed AGYW (n=56) customers about their interest in oral PrEP and the ring. Results: Among dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 18% of AGYW were married and 7% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children.Conclusions: Despite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.
Corrosion and Transformation of Solution Combustion Synthesized Co, Ni and CoNi Nanoparticles in Synthetic Freshwater with and without Natural Organic Matter
Authors: Khort Alexander , Hedberg Jonas , Mei Nanxuan , Romanovski Valentin , Blomberg Eva , Wallinder Inger Odnevall 
Published: December 2020

Abstract
Pure metallic Co, Ni, and their bimetallic compositions of Co3Ni, CoNi, and CoNi3 nanomaterials were prepared by solution combustion synthesis. Microstructure, phase composition, and crystalline structure of these nanoparticles (NPs) were characterized along with studies of their corrosion and dissolution properties in synthetic freshwater with and without natural organic matter (NOM). The nanomaterials consisted of aggregates of fine NPs (3–30 nm) of almost pure metallic and bimetallic crystal phases with thin surface oxide covered by a thin carbon shell. The nanomaterials were characterized by BET surface areas ranging from ~ 1 to 8 m2/g for the Ni and Co NPs, to 22.93 m2/g, 14.86 m2/g, and 10.53 m2/g for the Co3Ni, CoNi, CoNi3 NPs, respectively. More Co and Ni were released from the bimetallic NPs compared with the pure metals although their corrosion current densities were lower. In contrast to findings for the pure metal NPs, the presence of NOM increased the release of Co and Ni from the bimetallic NPs in freshwater compared to freshwater only even though its presence reduced the corrosion rate (current density). It was shown that the properties of the bimetallic nanomaterials were influenced by multiple factors such as their composition, including carbon shell, type of surface oxides, and the entropy of mixing.
Clinically Inapparent Right Heart Dysfunction is Associated with Reduced Myofilament Force Development in Coronary Artery Disease
Authors: Bening Constanze , Sales Virna , Alhussini Khaled , Radakovic Dejan , Benitez Rodolfo , Madrahimov Nodir , Keller Daniel , Leyh Rainer 
Published: December 2020

Abstract
Background: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We hypothesized that inapparent RV dysfunction in these patients is already associated with pathological changes at the level of myofilaments in concert with altered biomarkers of myocardial remodeling and endothelial dysfunction.Methods: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥20mm, n=178;TAPSE<20mm,n=40). Baseline serum samples for biomarkers (Galectin,TGFß1,N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements.Results: Patients with TAPSE <20mm had a higher incidence of DM (55vs34%,p=0.018), preoperative AFib (43vs16%,p=0.000), reduced GFR (67±18vs77±24 ml/min/1.73m2,p=0.013), larger LA area (22±6vs20±5cm2,p=0.005) and reduced LVEF (50vs55 %,p=0.008). Furthermore, higher serum ADMA (0.70±0.13vs0.65±0.15µmol/l, p=0.046) and higher serum Pentraxin-3 levels (3371±1068vs2681±1353pg/dl,p=0.004) were observed in these Patients. Skinned fibre force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5,p<0.01 and pCa 5.75 to 6.0,p< 0.05). Multivariable analysis revealed DM (OR 2.53 CI1.12-5.73, Euro Score II (OR1.34 CI 1.02-1.78), preoperative AF (OR4.86 CI2.06-11.47), GFR (OR7.72 CI 1.87-31.96), albumin (OR1.56 CI 0.52-2.60), Pentraxin-3 (OR19.68 CI14.13-25.24), depressed LVEF (OR8.61 CI 6.37-10.86), lower force values: (pCa 5.4; OR2.34 CI 0.40-4.29 and pCa 5.2; OR2.00 CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. Conclusions: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.
High Cytoplasmic FOXO3 Expression Associated with Poor Prognosis in Rectal Cancer Patients Received Preoperative Radiotherapy: A Study from Swedish Clinical Trial of Preoperative Radiotherapy to Big Database Analysis
Authors: Cui Weiyingqi , Xie Ning , Lam Eric. W.-F. , Hahn-Stromberg Victoria , Liu Na , Zhang Hong , Sun Xiao-Feng 
Published: December 2020

Abstract
Background: Accumulating evidence has implicated a pivotal role for FOXO3, FOXM1 and SIRT6 in cancer progression and metastasis. The majority of researches have focused on the functions of these proteins in drug resistance, but their relationships with radiotherapy (RT) response remain unclear. In this study, we examined the protein expression of FOXO3, FOXM1 and SIRT6 and their clinical significance in a Swedish rectal cancer trial of preoperative RT.Methods: Protein expression of FOXO3, FOXM1 and SIRT6 protein was examined by immunohistochemistry in tissue microarray (n =145). Genetic analysis of FOXO3, FOXM1 and SIRT6 were performed by cBioportal and MEXPRESS database. Gene-gene network analysis was conducted using GeneMANIA. Further functional enrichment analysis was performed based on LinkedOmics and Metascape online software.Results: The results showed that the FOXO3 and FOXM1 proteins were mainly expressed in the cytoplasm in both the normal and tumour tissues, and SIRT6 in both the cytoplasm and nucleus of the normal and tumour tissues. The FOXO3 and FOXM1 protein levels increased from the normal mucosa to the primary cancer (P < 0.001), while the SIRT6 protein decreased from the normal mucosa to the primary cancer (P < 0.001). High FOXO3 expression correlated with late TNM stage (P = 0.040) and distant metastasis (P = 0.032), as well as independently with disease free survival (RFS) in RT patients (HR = 7.948; P = 0.049; 95% CI = 1.002-63.032) but not in non-RT patients (P > 0.05). Furthermore, genetic analysis indicated that DNA methylation status contributes to the FOXO3 overexpression. Functional enrichment analysis demonstrated that FOXO3 is closely related to metabolism-related signalling pathway which is in turn associated with cancer radioresistance. Moreover, there were strong gene–gene interactions between FOXO3 and genes in metabolism-related signalling.Conclusions: Our findings suggest that FOXO3 may be a key predictive biomarker to optimise RT for rectal cancer patients to improve prognosis.Trial registration: Radiotherapy; 86151; Registered 17 November 1986; NCT00904813; https://clinicaltrials.gov/ct2/show/NCT00904813?term=Preoperative+Radiotherapy&cntry=SE&draw=3&rank=3.
Argininosuccinate Synthase 1 Suppresses Tumor Progression Through Activation of PERK/eIF2α/ATF4/CHOP Axis in Hepatocellular Carcinoma
Authors: Kim Sanghwa , Lee Minji , Song Yeonhwa , Lee Su-Yeon , Choi Inhee , Park I-Seul , Kim jiho , Kim Jin-sun , Kim Kang mo , Seo Haengran 
Published: December 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids.Methods: Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model.Results: Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism.Conclusion: These results demonstrate the critical functional roles for the arginine-metabolism–independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.
Efficacy and Mechanism of the Combination of PARP&nbsp;and CDK4/6 Inhibitors in the Treatment of Triple-negative Breast Cancer
Authors: ZHU XIUZHI , CHEN LI , Huang Binhao , Li Xiaoguang , Liu Yang , Hu Xin , Shao Zhimin , wang zhonghua 
Published: December 2020

Abstract
Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients with BRCA mutations and their efficacy is even more limited in triple-negative breast cancer (TNBC) due to clinical primary and acquired resistance. Here, we found that the efficacy of PARPi in TNBC can be improved with CDK4/6 inhibitors (CDK4/6i).Methods: We screened primary PARPi-sensitive and resistant cell lines from existing BRCAmut/TNBC cell lines and generated cells with acquired PARPi resistance by gradually increasing the concentration. The effects of the PARPi olaparib and the CDK4/6i palbociclib on BRCAmut/TNBC cell lines were examined in both sensitive and resistant cells in vitro and in vivo. Pathway and gene alterations were assessed mechanistically and pharmacologically.Results: We demonstrated for the first time that the combination of PARPi and CDK4/6i has synergistic effects against BRCAmut/TNBC both in vitro and in vivo. In the PARPi-sensitive MB436 cells, the single agent olaparib significantly inhibited cell viability and affected cell growth due to severe DNA damage. In the PARPi-resistant HCC1937 and SUM149 cells, single-agent olaparib was ineffective due to potential homologous recombination (HR) repair, and the combination of PARPi and CDK4/6i greatly inhibited HR during the G2 phase, increased DNA damage and inhibited tumor growth. Inadequate DNA damage caused by PARPi activated the Wnt signaling pathway and upregulated MYC. Further experiments indicated that the overexpression of β-catenin, especially its hyperphosphorylation at the Ser675 site activated the Wnt signaling pathway and mediated PARPi resistance, which could be strongly inhibited by the combined treatment with CDK4/6i.Conclusions: Our data provide a rationale for the clinical evaluation of the therapeutic synergy of PARPi and CDK4/6i in BRCAmut/TNBCs with high Wnt signaling activation, high MYC expression and do not respond to PARPi monotherapy.
The Effect of Learning Module Program on the Mothers’ Ability to Adapt New Foods, Feeding Styles, and Self-Efficacy to Their Children with Avoidant Restrictive Food Intake Disorder (ARFID)
Authors: prasetyo yoyok bekti , Nursalam Nursalam , Hargono Rahmat , Ahsan Ahsan 
Published: December 2020

Abstract
Purpose: This study is to examine the effects of learning module program on the mothers’ ability to adapt new foods, feeding styles, and self-efficacy to their children with Avoidant Restrictive Food Intake Disorder (ARFID).Methods: Quasi-experimental design without random sampling is used to evaluate the effectiveness of learning module program. There are 15 mothers take care of children with ARFID as experimental group given learning module program. The experimental group is conducted four meetings in four weeks. Each meeting has an effective 50 minutes. Fifteen mothers of control group are conducted home-visit by presenting the education of health to them. The control group intervention is performed two meetings. Meanwhile, the experimental group conducts pre-test and post-test. The data are analyzed by means of descriptive statistics, Chi-square test, Fisher’s exact test, Mann-Whitney U test and SPSS/WIN 22.0. Results: The participants of experimental group have showed bigger surge of new foods adaptation (t = -2.973, p < 0.003), feeding style (t = -4.646, p < 0.001), self-efficacy (t = -3.652, p = 0.001) than control group has.Conclusion: The findings indicated that the learning module program is deemed effective to improve mothers’ ability to adapt new foods, feeding styles, and self-efficacy to their children with ARFID.