bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Classification of Heterogeneous Slit-Illumination Images Using an Ensemble of Cost-Sensitive Convolutional Neural Networks
Authors: Jiang Jiewei , Wang Liming , Fu Haoran , Long Erping , Sun Yibin , Li Ruiyang , Li Zhongwen , Zhu Mingmin , Liu Zhenzhen , Chen Jingjing , Lin Zhuoling , Wu Xiaohang , Wang Dongni , Liu Xiyang , Lin Haotian
Published: September 2020

Background: Lens opacity seriously affects the visual development of infants. Slit-illumination images play an irreplaceable role in lens opacity detection; however, these images exhibited varied phenotypes with severe heterogeneity and complexity, particularly among pediatric cataracts. Therefore, it is urgently needed to explore an effective computer-aided method to automatically diagnose heterogeneous lens opacity and to provide appropriate treatment recommendations in a timely manner.Methods: We integrated three different deep learning networks and a cost-sensitive method into an ensemble learning architecture, and then proposed an effective model called ECCNN-Ensemble (ensemble of cost-sensitive convolutional neural networks) for automatic lens opacity detection. A total of 470 slit-illumination images of pediatric cataracts were used for training and comparison between the CCNN-Ensemble model and conventional methods. Finally, we used two external datasets (132 independent test images and 79 Internet-based images) to further evaluate the model’s generalizability and effectiveness.Results: Experimental results and comparative analyses demonstrated that the proposed method was superior to conventional approaches and provided clinically meaningful performance in terms of three grading indices of lens opacity: area (specificity and sensitivity; 92.00% and 92.31%), density (93.85% and 91.43%) and opacity location (95.25% and 89.29%). Furthermore, the comparable performance on the independent testing dataset and the internet-based images verified the effectiveness and generalizability of the model. Finally, we developed and implemented a website-based automatic diagnosis software for pediatric cataract grading diagnosis in ophthalmology clinics. Conclusions: The CCNN-Ensemble method demonstrates higher specificity and sensitivity than conventional methods on multi-source datasets. This study therefore provides a practical strategy for heterogeneous lens opacity diagnosis and has the potential to be applied to the analysis of other medical images.
The Germline/Somatic DNA Damage Repair Gene Mutations Modulate the Therapeutic Response in Chinese Patients with Advanced Pancreatic Ductal Adenocarcinoma
Authors: Shui Lin , Li Xiaofen , Peng Yang , Tian Jiangfang , Li Shuangshuang , He Du , Li Ang , Tian Bole , Li Mao , Yi Cheng , Cao Dan
Published: September 2020

Background: PDAC is a fatal disease with molecular heterogeneity, inducing differences in biological behavior and therapeutic strategy. NGS profiles of pathogenic alterations in Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precise medicine. Methods: NGS were performed on resected tissues or peripheral blood from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics, and survival status were collected. The Kaplan–Meier survival analyses were performed by the R version 3.6.1.Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed worse OS than those without (p=0.048). DDR deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n=9, 4.62%), ATM (n=8, 4.10%) and RAD50 genes (n=3, 1.54%). There was no significant improvement of OS between patients with or without DDR mutations (p=0.88). Treatment with platinum-based chemotherapy (p=0.0096) or olaparib (p=0.018) respectively improved the overall survival of patients with DDR mutation. No statistical correlation between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significiantly improved OS to DDR-mutated patients than intact DDR group (p=0.14). Conclusions: In this multi-center retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy. However, DDR alteration has shown limited value in prediction of hypermutational status and the sensitivity to PD-1 blockade.
Clinical Implications of Copy Number Alteration Detection Using Panel-Based Next-Generation Sequencing Data in Myelodysplastic Syndrome
Authors: Kim Yoo-Jin , Jung SeungHyun , Hur Eun-Hye , Choi Eun-Ji , Lee Kyoo-Hyung , Park Hyeon-Chun , Kim Hye-Jung , Kwon Yong-Rim , Park Silvia , Lee Sug Hyung , Chung Yeun-Jun , Lee Je-Hwan
Published: September 2020

Background: Recent advancements in next-generation sequencing (NGS) technologies allow the simultaneous identification of targeted copy number alterations (CNAs) as well as somatic mutations using the same panel-based NGS data. We investigated whether CNAs detected by the targeted NGS data provided additional clinical implications, over somatic mutations, in myelodysplastic syndrome (MDS). Methods: Targeted deep sequencing of 28 well-known MDS-related genes was performed for 266 patients with MDS. Results: Overall, 215 (80.8%) patients were found to have at least one somatic mutation; 67 (25.2%) had at least one CNA; 227 (85.3%) had either a somatic mutation or CNA; 160 had somatic mutations without CNA; and 12 had CNA without somatic mutations. Considering the clinical variables and somatic mutations alone, multivariate analysis demonstrated that sex, revised International Prognostic Scoring System (IPSS-R) and NRAS and TP53 mutations were independent prognostic factors for overall survival. For AML-free survival, these factors were sex, IPSS-R, and mutations in NRAS, DNMT3A, and complex karyotype/TP53 mutations. When we consider clinical variables along with somatic mutations and CNAs, genetic alterations in TET2, LAMB4, U2AF1, and CBL showed additional significant impact on the survivals. Conclusions: Our study suggests that the concurrent detection of somatic mutations and targeted CNAs may provide clinically useful information for the prognosis of MDS patients.
Knockdown of NUSAP1 Inhibits Cell Proliferation and Invasion Through Down-Regulation of TOP2A in Human Glioblastoma
Authors: Hu Yaotian , Xue Zhiyi , Qiu Chen , Feng Zichao , Qi Qichao , Wang Jiwei , Jin Wenxing , Zhong Zhaoyang , Liu Xiaofei , Li Wenjie , Zhang Qing , Huang Bin , Chen Anjing , Wang Jian , Yang Ning , Zhou Wenjing
Published: September 2020

Background: Nucleolar and spindle associated protein 1 (NUSAP1) is an indispensable mitotic regulator, which has been reported to be involved in the development, progression, and metastasis of several types of cancer. Here, we investigated the expression and biological function of NUSAP1 in human glioblastoma multiforme (GBM). Methods: The expression of NUSAP1 on GBM tissues and cells were determined by database analysis, immunohistochemistry and Western blot. EdU assay, transwell assay and flow cytometric analysis were performed to evaluate the effect of NUSAP1 knockdown on GBM cell proliferation, cell invasion and cell apoptosis. RNA sequencing was used to screen for downstream molecules altered in GBM cells after NUSAP1 depletion. An intracranial mice model and bioluminescent imaging were used to assess the effect of NUSAP1 on tumor growth and survival time in vivo. Results: Analysis of the molecular data in CGGA, TCGA and Rembrandt datasets demonstrated that NUSAP1 was significantly up-regulated in GBM relative to low grade gliomas and non-neoplastic brain tissue samples. Kaplan-Meier analysis indicated that patients with tumors showing high NUSAP1 expression exhibited significantly poorer survival in both CGGA (P = 0.002) and Rembrandt cohorts (P = 0.017). Analysis of RNA sequencing data from P3-cells with stable knockdown of NUSAP1 revealed topoisomerase 2A (TOP2A) as a possible molecule down-regulated by the loss of NUSAP1. SiRNA knockdown of either NUSAP1 or TOP2A in U251, T98 and GBM derived patient P3 cells inhibited GBM cell proliferation and invasion, and induced cell apoptosis. Finally, stable knockdown of NUSAP1 with shRNA led to decreased tumor growth in an orthotopic xenograft model of GBM in mice. Conclusions: Taken together, NUSAP1 gene silencing induced apoptosis possibly through the down-regulation of the candidate downstream molecule TOP2A. Interference with the expression of NUSAP1 might therefore inhibit malignant progression in GBM, and NUSAP1 might thus serve as a promising molecular target for GBM treatment.
Lnc-GULP1-2:1 Affects Granulosa Cell Proliferation by Regulating COL3A1 Expression and Localization​
Authors: Yao Guidong , Kong Yue , Yang Guang , Kong Deqi , Xu Yijiang , He Jiahuan , Xu Ziwen , Bai Yucheng , Fan Huiying , He Qina , Sun Yingpu
Published: September 2020

Backgrounds: Long non-coding RNA is a kind of RNA molecule with a transcript length of more than 200 nt and lacking protein coding ability. Recent studies have found that it is widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells and was lower expressed in patients with diminished ovarian reserve but highly expressed in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, which may be related to the regulation of cell cycle related genes CCND2 and p16. To further investigate the regulation of lnc-GULP1-2:1 on COL3A1, RNA analysis revealed a positive correlation between the expression of lnc-GULP1-2:1 and COL3A1 in multiple cell lines, and this was consistent in luteinized granulosa cells from patients with different ovarian functions. We also found that overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression and migration of COL3A1 into the nucleus. Silencing COL3A1 gene in KGN cells also significantly inhibited cell proliferation, which may be related to the regulation of CCND2 gene expression. Conclusions: This study demonstrates that lnc-GULP1-2:1 may participate in the regulation of granulosa cell proliferation by regulating the expression and localization of COL3A1 protein, which will provide a new idea for understanding the regulatory mechanism of follicular development and a new strategy for the diagnosis and treatment of diseases related to follicular development disorders in the future.
Determinants of Self-Reported Correct Knowledge About Tuberculosis Transmission Among Men and Women in Malawi: Evidence from a Nationwide Household Survey.
Authors: Ntenda Peter Austin Morton , Mussa Razak , Gowelo Steve , Sixpence Alick , Bauleni Andy , Simbeye Atusayi , Matengeni Alfred , Banda Godfrey , Stanley Christopher Chikhosi , Banda Susan , Nkoka Onkoka
Published: September 2020

Background: Correct knowledge about transmission of tuberculosis (TB) can influence better health-seeking behaviors, and in turn, it can aid TB prevention in society. Therefore, this study aimed to examine the prevalence and predictors of self-reported correct knowledge about TB transmission among adults in Malawi.Methods: We conducted a secondary analysis of the data obtained from the Malawi Demographic and Health Survey, 2015/16 (MDHS 2015/16). Questions regarding self-reported TB transmission were computed to evaluate the correct knowledge about TB transmission. The factors associated with the correct knowledge about Tb were assessed using univariate and multivariable logistic regression.Results: Overall, the prevalence of correct knowledge about TB transmission in the general population of Malawian adults was 61.5%. Specifically, the prevalence of correct knowledge about TB transmission was 63.6% and 60.8% in men and women, respectively. Those aged 35–44 years, having secondary or high education, belonging to the richest household, being exposed to mass media, being in professional/technical/managerial, having knowledge that “TB can be cured’, and those living in urban areas were significantly associated with correct knowledge about TB transmission.Conclusions: The findings of this study show that if appropriate strategies for TB communication and education to address the rural masses, young individuals, poor individuals, and individuals in the agriculture sector are put it place, can enhance TB prevention in Malawi.
Genetic Polymorphisms of Metabolic Enzyme Genes Associated with Leukocyte Mitochondrial DNA Copy Number in PAHs Exposure Workers
Authors: Li Xinling , Duan Xiaoran , Zhang Hui , Ding Mingcui , Wang Yanbin , Yang Yongli , Yao Wu , Xia Zhaolin , Zhou Xiaoshan , Wang Wei
Published: September 2020

Background: PAHs exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes’ genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated.Methods: We investigated the effects of metabolic enzymes’ genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using Real-time quantitative polymerase chain reaction method. Polymerase chain reaction and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867.Results: The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (P < 0.001). The 1-OHPYR had an increasing trend with the genotypes AA→AG→GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [b(95% CI) = -0.420 (-0.469, -0.372), P < 0.001], male [β(95% CI) = -0.058 (-0.103, -0.012), P = 0.013] ,and AA genotype for GSTP1 rs1695 [β(95% CI) = -0.051 (-0.095, -0.008), P = 0.020].Conclusions: The male was susceptibility to PAHs exposure. The AA genotype of GSTP1 rs1695 may influence the toxicity of PAHs and associated with the decreased of mtDNAcn.
Surgical Procedure of Segmentectomy as a Possible Cause of Postoperative Cerebral Embolism: A Case Report
Authors: Chen Peirui , Qing Qiushan , Diao Mingqiang , Sun Xiaokang , Yang Junrong , Lv Jing
Published: September 2020

Background: Cerebral embolism after lobectomy is a life-threatening complication during the early postoperative period. However, it is unclear if cerebral embolism can develop after segmentectomy. Case Presentation: We experienced a case of a 37-year-old man who demonstrated early symptom of acute ischemic stroke in early postoperative period after right upper posterior segmentectomy and performed intra-arterial mechanical thrombectomy (IAMT) successfully.Conclusions: long and irregular pulmonary vein stump (PVS) and endothelial injury caused by surgical procedure may lead to cerebral embolism after segmentectomy. We believe that doing preoperative pulmonary vascular assessment and using appropriate surgical procedure may reduce the rate of cerebral embolism.
PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer
Authors: Wei Xiao-li , Luo Xuan , Sheng Hui , Wang Yun , Chen Dong-Liang , Li Jia-Ning , Wang Feng-Hua , Xu Rui-Hua
Published: September 2020

Background: The outcomes of immune checkpoint inhibitors of patients with cancer liver metastases are poor, which may be related to a different tumor microenvironment from primary cancers. This study was aimed to analyze the PD-L1 expression and the immune microenvironment status in liver metastatic diseases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.Methods: 74 cases of pathologically confirmed colorectal cancer liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. Then, we evaluated the disparity between primary tumor and liver metastasis in PD-L1, CD4 and CD8 density and analyzed the factors associated with obvious disparity.Results: A total of 74 paired colorectal cancer with liver metastases were included in this study. The expression of PD-L1 in liver metastases was positively related to the density of CD4 and CD8. The expression of PD-L1 was higher in liver metastases than in primary tumors in certain subgroups of colorectal cancer, including the patients with concurrent liver metastases (n=63, p=0.05), receiving concurrent resection of primary and metastatic tumors (n=56, p=0.04). The two subgroups generally reflected those without inconsistent external influencing factors, such as treatment and temporal variation, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified, if any. Furthermore, tumor differentiation (moderate vs. poor: OR=0.23, 95% CI: 0.03-0.99, p=0.05)) were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and hepatic metastases.Conclusions: The expression of PD-L1 in the hepatic metastases was higher than in the primary tumors in subgroups reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was closely related to the tumor differentiation.
Long-term Health-related Quality of Life and Burden of Disease After Intensive Care: Development of a Patient-reported Outcome Measure.
Authors: Malmgren Johan A , Waldenström Ann-Charlotte , Rylander Christian , Johannesson Elias , Lundin Stefan
Published: September 2020

BackgroundICU survivorship includes a diverse burden of disease. To understand the extent of the problems, the right issues must be identified, and the right questions need to be asked to the patients. Current follow-up instruments lack detailed questions in several areas relevant to survivors. Our aim was to identify health-related problems relevant and unique to ICU survivors, and to construct a comprehensive questionnaire able to address these issues.Methods Thirty-three ICU survivors were interviewed at least six months after ICU discharge. All types of everyday dysfunctions and disabilities were extracted and compiled into a questionnaire. The questionnaire was tested on ICU survivors and non-ICU treated subjects. Inclusion criteria for the ICU survivors were an ICU stay of at least 72 hours with the ICU discharge six months to three years prior to the study. The non-ICU treated subjects were obtained from the Swedish Population Register, matched for age and sex. Eligible participants received an invitation letter and were contacted by phone. If willing to participate, they were sent the questionnaire. ResultsAnalysis of the interviews yielded 238 questions in 13 domains: cognition, fatigue, physical health, pain, psychological health, activities of daily life, sleep, appetite and alcohol, sexual health, sensory functions, gastrointestinal, urinary tract and work life.In total, 395 of 518 ICU survivors and 197 of 231 non-ICU treated subjects returned a completed questionnaire, the response rate being 76.2% and 85.3% respectively. The two groups differed significantly in 16 of 25 comorbidities. ICU survivors differed in a majority of questions (p ≤ 0.05) compared to non-ICU treated subjects, distributed over all 13 domains. ConclusionsThis study describes the first step in developing a designated questionnaire for identification of health-related quality of life issues and long-term burden of disease after intensive care. A first version of the questionnaire was answered by 395 ICU survivors. The questionnaire could identify that they experience severe difficulties in a wide range of domains compared to non-ICU treated subjects.Trial registrationClinicalTrials.gov Ref# NCT 02767180
Associations of worsening renal function with loop diuretics in patients with heart failure with different ejection fraction categories
Authors: Owusu-Ayeman Marvin , He Xin , Liang Weihao , Zhu Wengen , Wu Yuzhong , Xue Ruicong , Wu Zexuan , Dong Bin , Zhou Yuanyuan , Dong Yugang , Wei Fang-Fei , Liu Chen
Published: September 2020

Background

Heart failure patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) have different sensitivity to plasma volume change after decongestion, but the possible differential effects of loop diuretics dosage on worsening renal function (WRF) in heart failure (HF) categories remain unclear.
Methods

In 972 patients with HFpEF and 427 patients with HFrEF, we assessed the risk of WRF with the average daily furosemide equivalent dose, using multivariable logistic regression. WRF was defined as an increase in serum creatinine levels of more than 26.5 mmol/L during hospitalization.
Results

In patients with HFpEF and HFrEF, between-group differences in average daily furosemide equivalent dose (18.9 mg/d vs. 26.8 mg/d) and the prevalence of WRF (25.3% vs. 14.3%) were significant (p < 0.001). In multivariable-adjusted analyses, a doubling of the average furosemide equivalent dose was associated with higher risk of WRF in all patients, patients with HFpEF and HFrEF, with odds ratios amounting to 1.42, 1.41 and 1.60 (p ≤ 0.022), respectively. There was no interaction between heart failure categories and average furosemide equivalent dose (p = 0.37). The adjusted odds ratios of risk of WRF associated with intravenous furosemide were 1.26 (95% confidence interval [CI], 1.08–1.46; p = 0.002) in HFpEF but not significant in HFrEF(p = 0.099).
Conclusions

The risk of WRF was associated with higher furosemide dosage in both HF subtypes. Our observations highlight that close monitoring is required to prevent further renal impairment in all HF patients while using loop diuretics.
Association of Vitamin D Status and Cardio-Metabolic Risk Factors in Children and Adolescents: The CASPIAN-V Study
Authors: Qorbani Mostafa , Heidari-Beni Motahar , Ejtahed Hanieh-Sadat , Shafiee Gita , Goodarzi Farid , Zadeh Seyed Saeed Tamehri , Khademian Majid , Khonsari Nami Mohammadian , Motlagh Mohammad Esmaeil , Asayesh Hamid , Jabbari Mohammad , Heshmat Ramin , Ebrahimi Mehdi , Kelishadi Roya
Published: September 2020

Background: Metabolic syndrome (MetS) starts from early life, and is one of the important underlying factors for non-communicable disease (NCDs) in adulthood. Controversial evidence exists on the role of vitamin D deficiency in increasing risk of pediatric MetS. Objective: This study aimed to assess the relationship between vitamin D level with MetS and its components in children and adolescents. Methods: This cross-sectional nationwide study was performed as part of a surveillance program in Iran. Participants were 2596 students, aged 7 to 18 years, living in 30 provinces. In addition to filling questionnaires, physical examination was conducted, and blood samples were collected. Serum concentration of 25-hydroxy vitamin D (25(OH)D) was measured using direct competitive immunoassay chemiluminescene method.Results: 2596 students with mean age of 12.2 y (55.1% boys) were recruited. Prevalence of vitamin D deficiency and insufficiency in participants was 10.6% (n=276), and 60.5% (n=1570), respectively. Prevalence of MetS was higher in vitamin D deficient group. Students with deficient vitamin D level had higher odds of MetS (OR: 4.25, 95%CI: 2.26-7.98), abdominal obesity (OR: 2.24, 95%CI: 1.61-3.12), low HDL-C (OR: 1.65, 95%CI: 1.18-2.30) and high fasting blood sugar (OR: 2.56, 95%CI: 1.43-4.57) in comparison to those with sufficient level of vitamin D.Conclusion: Vitamin D deficiency was associated with increased odds of MetS and its components in Iranian pediatric population. These findings underscore the importance of prevention and control of vitamin D deficiency in preventative programs against NCDs.
Skilled Delivery Care Service Uptake Among Socially Marginalized Women in Kambata-Tembaro Zone, Southern Ethiopia
Authors: Alemu Abebe , Assefa Biruk , Ahmed Ritbano , Mossa Hasen , Gebeyehu Negesso
Published: September 2020

Background: Globally, 358,000 women die during pregnancy and childbirth every year. Poor skilled delivery health care uptake remains a significant problem in developing countries. In Ethiopia, skilled delivery care service uptake was law. Marginalized women are vulnerable for poor delivery care uptake and addressing woman’s’ social marginalization could play an important role in increasing uptake of skilled delivery care service among minorities in the study area. Thu, the study was aimed to access the utilization of delivery care uptake and associated factors among women from socially marginalized minorities in the Kambeta-Temabaro, Zone Southern Ethiopia. Methods: Community based cross-sectional study was conducted from April 01 to March 30, 2019. Multistage sampling procedure was employed to enroll 521 study participants. An interviewer administered questionnaire was used to collect the data. Data was entered using EPI- INFO and exported to Statistical Package for Social Science (SPSS)-21 for analysis. The degree of association was assessed using odds ratio with 95% confidence interval and the variable with p-value <0.05 were declared as statistically significant. The model fitness was checked using Pearson’s Chi-square with the value of 3.45 and significance 0.026 Result: The magnitude of skilled delivery care service uptake among socially marginalized minorities was 19% in the study area. Maternal education, occupation, and awareness on delivery care, pregnancy plan, and number of birth, mothers’ life-style, and social discrimination were significantly associated with the delivery care service uptake among women from socially marginalized minorities. Conclusion: The prevalence of the delivery service utilization among marginalized mothers was found to be low [19%]. Mothers’ education, occupation, life-style, awareness, number of birth and social discrimination was significantly associated with delivery service uptake from health facilities in Kambata-Tembaro zone, Southern Ethiopia. Thus, intervention on social discrimination in the community to breakthrough core barriers; improving women awareness though health education and promotion; and accessing education and employment for women are highly recommended.
Spatial Distribution and Time Series Analysis of COVID-19 Pandemic in Italy: A Geospatial Perspective
Authors: Moazzam Muhammad Farhan Ul , Paracha Tamkeen Urooj , Rahman Ghani , Lee Byung Gul , Farid Nasir , Arshad Adnan
Published: September 2020

The novel coronavirus pandemic disease (COVID-19) affected the whole globe, though there is lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of COVID-19 infected patients show mild to moderate symptoms and they get better without any medical assistance due to better immune system to generate antibodies against the novel coronavirus. In this study the active cases, serious cases, recovered cases, deaths and total confirmed cases have been analyzed using geospatial technique (IDW) with the time span of 2nd March to 3rd June 2020. As on 3rd June the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951 and active cases were 39,177 which has been reported by the Ministry of health, Italy. March 2nd – June 3rd 2020 a sum of 231, 238 cases has been reported in Italy out of which 38.68% cases reported in Lombardia region with death rate of 18% which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%) and Trento (84.54%). The COVID-19 evolution in Italy has been particularly found in the major urban area i.e. Rome, Milan, Naples, Bologna and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and the recovered cases. Thus, monitoring and planning using geospatial technique is very important to control COVID-19 spread in the country.
The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination
Authors: Zhang Yeyu , Zhu Yuxing , Xiao Mengqing , Cheng Yaxin , He Dong , Liu Jianye , Xiang Liang , Gong Lian , Wang Zhanwang , Deng Liping , Cao Ke
Published: September 2020

BackgroundBladder cancer (BC) is the most common malignant tumor of the urinary system. Increasing evidence indicates long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis, development, and progression. However, the role of TMPO antisense RNA 1 (TMPO-AS1) is still need to be explored in BC.MethodsThe lncRNA TMPO-AS1 expression was evaluated by bioinformatics analysis and further validated by qRT-PCR. Loss- and gain-of- function assays were performed to determine the biological functions of TMPO-AS1 in BC proliferation, migration, and invasion. Chromatin immunoprecipitation, luciferase reporter assays, western blotting, RNA pull-down, RNA immunoprecipitation assays, and fluorescence in situ hybridization were conducted to explore the molecular mechanisms of TMPO-AS1/E2F transcription factor 1 (E2F1) loop. ResultsTMPO-AS1 is upregulated in bladder cancer and is associated with BC patients’ poor prognoses. Functional experiments demonstrated that TMPO-AS1 promotes bladder cancer cell proliferation, migration, invasion, and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for the TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization, thereby promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.ConclusionsOur study is the first to uncover a novel positive regulatory loop of TMPO-AS1/E2F1 important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.
A cross-sectional study of the prevalence, density and risk factors associated with malaria transmission in urban communities of Ibadan, Southwestern Nigeria
Authors: Awosolu Oluwaseun , Yahaya Zary Shariman , Termizi Farah Haziqah Meor , Simon-Oke Iyabo Adepeju , Fakunle Comfort
Published: September 2020

Background
Malaria is a serious global public health challenge which causes great morbidity and mortality worldwide particularly in sub-Saharan Africa. This study was designed to determine the prevalence, parasite density and risk factors associated with malaria infection transmission among residents of two urban communities of Ibadan, southwestern Nigeria.
Methods
A cross-sectional hospital-based study was carried out on 300 participants. Blood samples were obtained. Thick and thin blood films were prepared and viewed using the standard parasitological technique of microscopy. Moreover, data on sociodemographic and environmental variables were obtained using standard questionnaire.
Results
Of the 300 participants examined, a total of 165 (55.0%) were found positive for Plasmodium falciparum with a mean (S.D) parasite density of 1814.70 (1829.117) parasite/µL of blood. The prevalence and parasite density of malaria infection was statistically significant (P < 0.05) in relation to age group. Obviously, malaria infection decreases as age increasing with ≤ 5 years having the highest prevalence and mean parasite density. Similarly, in relation to gender, males significantly (P < 0.05) had higher prevalence (60.2%) and mean (S.D) parasite density of malaria infection [2157.73 (1659.570) parasite/µL of blood] compared to females. Additionally, those without formal education had the highest prevalence (73.0%) and mean (S.D) parasite density of infection [2626.96 (2442.195) parasite/µL of blood]. The binary logistic regression analysis showed that age group 6–10 (COR 0.066, 95% CI: 0.007–0.635), presence of streams (COR 0.225, 95% CI: 0.103–0.492), distance from streams within ≤ 1 Km (COR 0.283, 95% CI: 0.122–0.654) and travel to rural area (COR 4.689, 95% CI: 2.430–9.049) were the major risk factors.
Conclusions
Malaria infection is apparently endemic in the study area and greatly influenced by rural-urban movement. Multifaceted and integrated control strategy should be adopted. Health education on mosquito prevention and use of chemoprophylaxis before and during travel to rural areas are important.
Transcriptome Analysis of the Liver of Eospalax Fontanierii Under Hypoxia
Authors: Hao Zhiqiang , Xu Lulu , He Jianping , Li Guanglin , Li Jingang
Published: September 2020

BackgroundHypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawle rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia adaptation in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5%, 10.5%, and 21%).ResultsBased on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of hub genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. ConclusionsWe characterized the E. fontanierii liver transcriptomes and profiled the changes in gene expression in the liver under different oxygen levels. Functional enrichment analysis showed that the main functions (steroid catabolic process, lipid metabolic process, primary bile acid biosynthesis, energy production and amino acid metabolic) of the liver were regulated in response to hypoxia. We identified multiple important DEGs underlying the potential molecular adaptation mechanisms to hypoxia, including genes associated with anti-apoptosis, energy supply, anti-inflammation, and anti-oxidation. Our results provide a comprehensive understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.
Comparison of Reversal of Rat Pulmonary Fibrosis of Nintedanib, Pirfenidone and Human Umbilical Mesenchymal Stem Cells from Wharton’s Jelly
Authors: Chu Kuo-An , Yeh Chang-Ching , Kuo Fu-Hsien , Lin Wen-Ren , Hsu Chien-Wei , Chen Tien-Hua , Fu Yu-Show
Published: September 2020

Background:The present study compared the effects of antifibrotic medications, pirfenidone and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).Methods:A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5 × 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on Day 21 following BLM damage.Results:Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.Conclusions:Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with significant better result in lung volume, pathological changes, lung function and blood oxygen saturation.
Transmission potential of Mayaro virus by Aedes albopictus, and Anopheles quadrimaculatus from United States
Authors: Dieme Constentin , Ciota Alexander T , Kramer Laura D
Published: September 2020

Background Mayaro virus (MAYV; Alphavirus, Togaviridae) is an emerging pathogen endemic in South American countries. The increase in intercontinental travel and tourism-based forest excursions has resulted in an increase in MAYV spread, with imported cases observed in Europe and North America. Intriguingly, no local transmission of MAYV has been reported outside South America, despite the presence of potential vectors.Methods We assessed the vector competence of Aedes albopictus from New York and Anopheles quadrimaculatus for MAYV. Results We showed that Aedes albopictus from New York and Anopheles quadrimaculatus are competent vectors for MAYV. However, Aedes albopictus was more susceptible to infection. Transmission rates increased with time for both species with rates of 37.21% and 64.44% for Aedes albopictus, and 31.11% and 46.34% for Anopheles quadrimaculatus, respectively, at 7 and 14 days-post-infection. Conclusions Our results suggest there is a risk of further MAYV spread throughout the Americas and autochthonous transmission in the United States. Preventive measures such as mosquito surveillance of MAYV will be essential for early detection.
Awareness and Attitudes Toward HIV Self-Testing in Northern Thailand
Authors: Shafik Nardeen , Deeb Savana , Srithanaviboonc Kriengkrai , Ayood Pisittawoot , Malasao Rungnapa , Siviroj Penprapa , Musumari Patou Masika , Wood Michele M
Published: September 2020

HIV self-testing (HIVST) was recently introduced in Thailand, but little is known about receptivity among its residents. Because HIV testing is a critical component of HIV prevention, it is important to understand how HIVST is perceived among potential users. The purpose of this study was to examine awareness and attitudes toward HIVST among adults in Northern Thailand. A convenience sample of 403 adult residents of the Sanpatong district, Chiang Mai province was interviewed using a structured questionnaire in 2019. Awareness of HIVST was low (14%), as was the overall HIVST negative attitude score (6.44; possible range of 0-14). The odds of being aware of HIVST were more than twice as high for those with more education compared to those with less (AOR=2.29, 95% CI: 1.22 - 4.30), and roughly half as high for those who expressed HIV stigma compared to those who did not (AOR=0.49, 95% CI: 0.26 - 0.91). Holding negative attitudes towards HIVST also was associated with lower education and expressing HIV stigma, but these relationships disappeared in multivariate analysis. Findings may be used by local health organizations to tailor HIVST education efforts.
Changes of Peripheral Lymphocyte Populations in Patients with Advanced/Recurrent Ovarian Cancer Undergoing Splenectomy During Cytoreductive Surgery
Authors: Chen Wei , Ye Shuang , Wu Yutuan , Pei Xuan , Xiang Libing , Ping Bo , Shan Boer , Yang Huijuan
Published: September 2020

Background: To investigate the change of peripheral lymphocyte subsets after splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancers Methods: We enrolled 83 patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery. Twenty patients who also underwent splenectomy were assigned to the splenectomy cohort and the rest to the non-splenectomy cohort. Flow cytometry was used to measure the peripheral lymphocyte subsets consisting of T cells, regulatory T cells, natural killer cells, B cells, and activation antigens before and after surgery. Results: There wasn’t any difference in the number and distribution of peripheral lymphocyte subsets between the two cohorts before surgery. We observed elevated levels of T cells (CD3+, CD3+CD8+) in the splenectomy cohort compared to those in the non-splenectomy cohort after surgery, which achieved statistical significance. CD8+CD28+ T cells had a significant decreasing tendency (P=0.011) while CD3+/HLA-DR+ T cells were the opposite (P=0.001) in the splenectomy cohort. The proportion of Tregs (P=0.005) and B cells (P<0.001) including CD3-/HLA-DR+ B cells (P=0.007) increased after surgery, and the absolute number of T cells and NK cells decreased to different extents (P<0.001) in the non-splenectomy cohort. The post-operative percentage of CD8+CD28+ T cells was less than the pre-operative one (P=0.022), which was similar to the splenectomy cohort. Conclusions: The changes in peripheral lymphocyte populations were different between patients with and without splenectomy during cytoreductive surgery for ovarian cancers. T cells were increased and activated in splenectomy cohort, whereas, B cells were increased and activated in non-splenectomy.
Combining Gene Expression Signature With Clinical Features for Survival Stratification of Gastric Cancer
Authors: Sun Qiang , Guo Dongyang , Li Shuang , Xu Yanjun , Jiang Mingchun , Li Yang , Duan Huilong , Zhuo Wei , Liu Wei , Zhu Shankuan , Liu Xiangrui , Wang Liangjing , Zhou Tianhua
Published: September 2020

Background: The AJCC staging system is considered as the golden standard in clinical practice. However, it remains some pitfalls in assessing the prognosis of gastric cancer (GC) patients with similar clinicopathological characteristics. We aim to develop a new clinic and genetic risk score (CGRS) to improve the prognosis prediction of GC patients.Methods: The gene expression profiles of the training set from the Asian Cancer Research Group (ACRG) cohort were used for developing genetic risk score (GRS) by LASSO-Cox regression algorithms. CGRS was established by integrating GRS with clinical risk score (CRS) derived from Surveillance, Epidemiology, and End Results (SEER) database. GRS and CGRS were validated in ACRG validation set and other four independent GC cohorts with different data types, such as microarray, RNA sequencing, and qRT-PCR. Multivariable Cox regression was adopted to evaluate the independence of GRS and CGRS in prognosis evaluation.Results: We established GRS based on a nine-gene signature including APOD, CCDC92, CYS1, GSDME, ST8SIA5, STARD3NL, TIMEM245, TSPYL5, and VAT1. GRS and CGRS dichotomized GC patients into high and low risk groups with significantly different prognosis in four independent cohorts, including our Zhejiang cohort (all HR > 1, all P < 0.001). Both GRS and CGRS were prognostic signatures independent of the AJCC staging system. Receiver operating characteristic (ROC) analysis showed that area under ROC curve of CGRS was larger than that of the AJCC staging system in most cohorts we studied. Nomogram and web tool (http://39.100.117.92/CGRS/) based on CGRS were developed for clinicians to conveniently assess GC prognosis in clinical practice.Conclusions: CGRS integrating genetic signature with clinical features shows strong robustness in predicting GC prognosis, and can be easily applied in clinical practice through the web application.
Peer Support Workers as a Bridge: A Qualitative Study Exploring the Role of Peer Support Workers in the Care of People Who Use Drugs During and After Hospitalization 
Authors: Lennox Robin , Lamarche Larkin , O'Shea Tim
Published: September 2020

Background: To describe the key qualities and unique roles of peer support workers in the care of people who inject drugs during and after hospitalization.Methods: We conducted a qualitative study. Key stakeholders were recruited including: people who use drugs who had been hospitalized, healthcare team members, peer support workers, and employers of peer support workers. Data was collected from 2019-2020 using semi-structured interviews that were audio-recorded, transcribed, and analyzed thematically.Results: Fourteen participants were interviewed: 6 people who use drugs who had been hospitalized, 5 healthcare team members, 2 peer support workers, and 1 employer of peer support workers. At the core of the data was the notion of peer workers acting as a bridge to overcome systemic barriers. We found two themes that related to functions of this bridge: advocacy and navigating transitions within the healthcare system. We found two themes for building a strong bridge and making the role of a peer support worker function effectively (training and mentorship, and establishing boundaries). We found three themes involving characteristics of an effective peer worker (intrinsic qualities, contributions of shared experiences, and personal stability). When the bridge works well it ultimately serves to rebuild trust between healthcare providers and people who use drugs.Conclusions: Peer support workers are highly valued by both people who use drugs and members of the healthcare team. Peer support workers act as a bridge between patients and healthcare providers, and are critical in establishing trust, easing transitions in care, and providing unique supports to people who use drugs during and after hospitalization.