bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Automated Microvascular Flow Analysis Software AVA 4.0: A Validation Study
Authors: Guay Christian S. , Khebir Mariam , Shahiri Shiva , Szilagyi Ariana , Cole Erin Elizabeth , Bracco David , Simoneau Gabrielle , Badawy Mohamed 
Published: September 2020

Abstract
BACKGROUND: Real-time automated analysis of videos of the microvasculature is an essential step in the development of research protocols and clinical algorithms that incorporate point-of-care microvascular analysis. Validation studies on the software packages developed to perform these analyses have reported low agreement with the current referent standard semi-automated analysis method. In response to the call for validation studies of available automated analysis software by the European Society of Intensive Care Medicine, we report the first human validation study of AVA 4.0. METHODS: Two retrospective perioperative datasets of human microcirculation videos (P1 and P2) and one prospective healthy volunteer dataset (V1) were used. Video quality was assessed using the Microcirculation Image Quality Selection (MIQS) score. Videos were initially analysed with (1) AVA software 3.2 by two experienced users through a semi-manual method, followed by an analysis with (2) AVA automated software 4.0 for perfused vessel density (PVD), total vessel density (TVD), and proportion of perfused vessels (PPV). Bland-Altman analysis and intraclass correlation coefficients (ICC) were used to measure agreement between the two methods. Each method’s ability to discriminate between microcirculatory states before and after induction of general anesthesia was assessed using paired t-tests. RESULTS: Fifty-two videos from P1, 128 videos from P2 and 26 videos from V1 met inclusion criteria for analysis. Correlational analysis and Bland Altman analysis revealed poor agreement and no correlation between AVA 4.0 and AVA 3.2. Increasing video length did not improve agreement. Automated analysis consistently underestimated measures of vessel density. Following the induction of anesthesia, TVD and PVD measured using AVA 3.2 increased significantly for P1 and P2 (p < 0.05). However, these changes could not be replicated with the data generated by AVA 4.0. CONCLUSIONS: AVA 4.0 is not a suitable tool for research or clinical purposes at this time. Future validation studies of automated microvascular flow analysis software should aim to measure the new software’s agreement with the referent standard, its ability to discriminate between clinical states and the quality thresholds at which its performance becomes unacceptable.
Decreased Serum Growth Differentiation Factor 15 Levels After Lifestyle Intervention in Patients With Newly Diagnosed Type 2 Diabetes Mellitus
Authors: He Xingxing , Su Jiaorong , Ma Xiaojing , Lu Jingyi , Wang Yufei , Yin Jun , Bao Yuqian , Hu Gang , Zhou Jian 
Published: September 2020

Abstract
Background: Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of lifestyle intervention (LI) or LI combined with breakfast meal replacement (LI+MR) in newly diagnosed type 2 diabetes patients. Methods: A total of 84 patients with available serum samples at both baseline and Week 4 were enrolled in this biomarker substudy. All subjects underwent a 2-hour 75g oral glucose tolerance test at baseline and Week 4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. Results: After 4-weeks of LI, GDF15 levels overall significantly decreased compared with baseline (P<0.05). ∆GDF15 levels were significantly and negatively associated with baseline GDF15 levels (r=–0.450, P<0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4-weeks of LI was 904.57 pg/ml, with an area under curve of 0.699. Based on the cut-off point of 900 pg/ml, patients with baseline GDF15 ≥900 pg/ml had significantly decreased GDF15 levels after LI, while those <900 pg/ml had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/ml. Conclusions: LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/ml.Trial registration: ClinicalTrials.gov, NCT02248714. Registered 25 September 2014 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02248714?term=NCT02248714&draw=2&rank=1
Mechanisms of Compound Kushen Injection for Treatment of Bladder Cancer Based on Bioinformatics and Network Pharmacology With Experimental Validation
Authors: Zhang Lihui , Zhang Wanying , Xiong Jiaming , Duan Xiumei , Hai Lina , Zhang Yuliang , Zhang Miaomiao , Qin Guifang , Zhang Guowei 
Published: September 2020

Abstract
Background: Bladder cancer is the most common malignant neoplasm of the urinary system. CompoundKushen injection (CKI) is a Chinese medicinal preparation that has been used clinically to treat varioustypes of cancers for more than 20 years. However, the pharmacological effect of CKI on bladder cancerrequires further clarification.Methods: Network pharmacology combined with bioinformatics was used to elucidate the therapeuticmechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI is effective againstbladder cancer was further verified in vitro using the human bladder cancer cell line T24.Results: Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data mining revealed 5500 differentially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerts anti-bladder cancer effects byregulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated thatCKI has a therapeutic effect on bladder cancer by synergistically regulating certain biological processes,including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes andGenomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Aktsignaling pathway. Consistently, cell experiments indicated that CKI could inhibit proliferation andmigration of T24 bladder cancer cells, and induce their apoptosis. Moreover, RT-qPCR and western blotresults indicated that CKI may treat bladder cancer by downregulating gene and protein expression levels,respectively of MMP-9, JUN, EGFR, and ERK1.Conclusions: CKI can inhibit proliferation and migration, and induce apoptosis of T24 bladder cancer cellsthrough multiple biological pathways and targets. CKI also has significant effects on regulation of key genesand proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen currentunderstanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
HER2 Nuclear Translocation and Decreased T-DM1 Efficacy in HER2 Positive Advanced Breast Cancer Treated with Dual HER2 Blockade. The SePHER Study.
Authors: Bon Giulia , Pizzuti Laura , Laquintana Valentina , Loria Rossella , Porru Manuela , Marchiò Caterina , Krasniqi Erisled , Barba Maddalena , Maugeri-Saccà Marcello , Gamucci Teresa , Berardi Rossana , Livi Lorenzo , Ficorella Corrado , Natoli Clara , Cortesi Enrico , Generali Daniele , Verde Nicla La , Cassano Alessandra , Bria Emilio , Moscetti Luca , Michelotti Andrea , Adamo Vincenzo , Zamagni Claudio , Tonini Giuseppe , Barchiesi Giacomo , Mazzotta Marco , Marinelli Daniele , Tomao Silverio , Marchetti Paolo , Valerio Maria Rosaria , Mirabelli Rosanna , Russo Antonio , Fabbri Maria Agnese , D'Ostilio Nicola , Veltri Enzo , Corsi Domenico , Garrone Ornella , Paris Ida , Sarobba Giuseppina , Giotta Francesco , Garufi Carlo , Cazzaniga Marina , Medico Pietro Del , Roselli Mario , Sanguineti Giuseppe , Sperduti Isabella , Sapino Anna , De Maria Ruggero , Leonetti Carlo , Leo Angelo Di , Ciliberto Gennaro , Falcioni Rita , Vici Patrizia 
Published: September 2020

Abstract
Background: ErbB2-targeting agents have dramatically changed the therapeutic landscape of ErbB2+ advanced breast cancer (ABC). However, their optimal sequence of administration deserves further investigation.Methods: The biology of ErbB2 was investigated through sequential treatments in vitro, in ErbB2+ breast cancer cell lines resistant to trastuzumab, pertuzumab, and their combination. We analyzed data from 555 ErbB2+ ABC patients treated with trastuzumab emtansine (T-DM1) and explored the efficacy of T-DM1 in the 371 patients who received it in second-line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models.Results: We show here lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Reduced T-DM1 efficacy is associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. Membrane-HER2 downregulation was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in first-line, and 74 and 10 months in 194 pertuzumab-naïve patients (p=0.0006 and 0.03 for OS and PFS2, respectively). Conclusions: Our data support the hypothesis that the addition of pertuzumab to trastuzumab reduces the amount of available plasma membrane HER2 receptor, limiting the binding of T-DM1 to cancer cells. This may help interpret the less favorable outcomes of second-line T-DM1 in trastuzumab/pertuzumab pre-treated patients compared to their pertuzumab-naïve counterpart.
Depression and Anxiety Among Pregnant Mothers in the Initial Stage of the Coronavirus Disease (COVID-19) Pandemic in Southwest of Iran
Authors: Maharlouei Najmeh , Keshavarz Pedram , Lankarani Kamran B. 
Published: September 2020

Abstract
‌Background: Women are at higher risk for depression progression especially during pregnancy. So, we aimed to investigate depression, anxiety, and stress level of pregnant mothers in the initial stage of the COVID-19 infection in Southwest of Iran. Methods: This cross-sectional study conducted during March and April, 2020 in Shiraz, Iran. Pregnant mothers registered in maternity clinics affiliated to Shiraz University of Medical Sciences were included. An online self-administered checklist was used. It included socio-demographic, obstetric and medical history, and the short form of Depression Anxiety Stress Scales (DASS-21) for evaluation of depression, anxiety, and stress. P-value < 0.05 was considered significant.Results: 540 pregnant mothers answered the questionnaire. 83.5% had no comorbidity. Abnormal depression score was significantly higher in those who did not have any insurance (OR= 2.5) and in those with poor self-rated health (SRH) (OR= 27.8). Pregnant mothers with lower SRH and two or more comorbidities had higher chance of having abnormal level of anxiety subscale; 6.9, 3.7 times, retrospectively. Conclusion: The study revealed that that abnormal level of depression was associated with SRH and medical insurance status. Moreover, the number of comorbidities and poor SRH were significantly increased the chance of achieving abnormal anxiety level in pregnant mothers during the COVID-19 pandemic.
Factors Influencing Contraceptive Decision Making and Use Among Young Adolescents in Urban Lilongwe, Malawi: A Qualitative Study
Authors: Dombola Gift Mtawali , Chipeta Effie , Manda Wanangwa Chimwaza 
Published: September 2020

Abstract
Background: The prevalence of teenage pregnancies in Malawi is 29% and about 25% of married and 30% of unmarried adolescents (15-19) use contraceptives. Data on contraceptive use has focused on older adolescents (15-19) leaving out the young adolescents (10-14). This study assessed factors that influence contraceptive decision-making and use among young adolescents aged 10-14 years.Methods: This was a qualitative study which used Theory of Reasoned Action (TRA) model to understand the processes that influence contraceptive decision making among young adolescents (10-14) in urban Lilongwe. The study was conducted in 6 youth health friendly service centers and in 12 youth clubs. Two focus group discussions and 26 in-depth interviews were conducted among sexually-active in and out of school young adolescents and key informants. The results are organized into themes identified during analysis.Results: Results showed that contraceptive decision making is influenced by social factors (individual, interpersonal, society) and adolescents` perceptions regarding hormonal contraceptives. There is also disconnect between Education and adolescent Sexual and Reproductive Health policies.Conclusion: The findings suggest the need for empowering girls in decision making, addressing myths around contraceptives, and harmonization of Education and Sexual and Reproductive Health policies in the country.
LINE1 Methylation is Associated With Lead Exposure and Certain Job-Tasks Performed by Electronic Waste Workers
Authors: Issah Ibrahim , Arko-Mensah John , Rozek Laura S. , Zarins Katie R. , Agyekum Thomas P. , Dwomoh Duah , Basu Niladri , Batterman Stuart , Robins Thomas G. , Fobil Julius N. 
Published: September 2020

Abstract
Background: Electronic waste recycling processes such as dismantling with rudimentary tools and open-air burning result in the release of several toxic chemicals into the environment. Exposure to these toxic chemical mixtures has been associated with many adverse health outcomes affecting respiratory, cardiovascular, neurological, and reproductive systems. DNA methylation has been associated with exposure to toxic chemicals, including heavy metals in several epidemiological studies. DNA methylation profile due to exposure to toxic chemicals among e-waste recyclers has not been studied.Objective: This study assessed the associations between blood and urine levels of heavy metals; cadmium (Cd), lead (Pb), and arsenic (As) and methylation levels of the LINE1 gene among e-waste and control populations in Ghana.Methods: The study enrolled 100 male e-waste workers and 51 all-male non e-waste workers or controls. Body burden of Cd, Pb and As was measured in blood and urine using Inductively Coupled Plasma Mass Spectrometry, while LINE1 methylation levels were assessed by pyrosequencing of bisulfite-converted DNA extracted from whole blood.Results: There was no significant difference in LINE1 methylation between the e-waste and the non e-waste workers (85.16% ±1.32 vs 85.17% ±1.11, p = 0.950). However, CpG1 showed significantly lower mean methylation among controls, compared to e-waste workers (81.70% ±1.86 vs 82.48% ±2.20, p = 0.034). In linear regression models, blood lead (B-Pb) level was significantly inversely associated with overall LINE1 methylation (β = -0.004; 95%CI: -0.008, -0.0003; p = 0.034). Among e-waste recyclers, collectors showed significantly reduced LINE1 methylation levels (β = -0.889; 95%CI: -1.757, -0.021; p = 0.045). Conclusion: Continuous exposure to Pb may interfere with LINE1 methylation leading to epigenetic alteration, thus serve as an early epigenetic marker for future adverse health outcomes.
Long Noncoding RNA SNHG12 is a Potential Diagnostic and Prognostic Biomarker in Various Tumors
Authors: Wang XinZhuang , Jiang Qiuyi , Zhang Cheng , Yang Quan , Wang Lixiang , Zhang Jian , Wang Ligang , Chen Xin , Hou xu , Han Dayong , Wu Jianing , Zhao Shi Guang 
Published: September 2020

Abstract
Background. Tumors are the second most common cause of death in humans worldwide, second only to cardiovascular and cerebrovascular diseases. Although methods and techniques for the treatment of tumors continue to improve, the effect is not satisfactory. These may lack effective therapeutic targets. This study aimed to evaluate the value of SNHG12 as a biomarker in the prognosis and clinical characteristics of various cancer patients.Methods. We analyzed SNHG12 expression and plotted the survival curves of all cancer samples in the TCGA database using the GEPIA tool. Then, we searched for eligible papers up to April 1, 2019 in databases. Next, the data were extracted from studies examining SNHG12 expression, overall survival and clinicopathological features in patients with malignant tumors. We used Review Manager 5.3 and Stata 15 software to analyze the statistical data.Results. In the TCGA database, abnormally high expression of SNHG12 in tumor samples indicates that the patient has a poor prognosis. Results of meta-analysis is that SNHG12 high expression is related to low overall survival (HR=2.72, 95% CI=1.95-3.8, P<0.00001), high tumor stage (OR=3.94, 95% CI=2.80-5.53, P<0.00001), high grade (OR=2.04, 95% CI=1.18-3.51, P=0.01), distant metastasis (OR=2.20, 95% CI=1.40-3.46, P=0.0006), tumor size (OR=2.79, 95% CI=1.89-4.14, P<0.00001) and lymph node metastasis (OR=2.66, 95%CI=1.65-4.29, P<0.0001).Conclusions. Our study confirmed that the high expression level of SNHG12 is closely related to the clinicopathological characteristics and prognosis of patients and is a new predictive biomarker for various cancer patients.
COVID-19 during pregnancy should we really worry from vertical transmission or rather from fetal hypoxia and placental insufficiency? A systematic review and meta -analysis
Authors: AbdelMassih Antoine , Fouda Raghda , Essam Rana , Negm Alhussein , Khalil Dalia , Habib Dalia , Afdal George , Ismail Habiba-Allah , Aly Hadeer , Genedy Ibrahim , Qadi Layla El , Makki Leena , Shulqamy Maha , Hanafy Maram , AbdelMassih Marian , Ibrahim Marina , Ebaid Mohamed , Ibrahim Monica , El-Husseiny Nadine , Ashraf Nirvana , Shebl Noura , Menshawey Rahma , Darwish Rama , ElShahawi Rana , Ramadan Rana , Albala Sadra , Imran Salwa , Ahmed Sama , Khaldi Samer , Abohashish Sara , Paulo Stavro , Omar Yasmin , Tadros Mourad Alfy 
Published: September 2020

Abstract
Background:COVID-19 is the largest outbreak to strike humanity. The wide scale of fatalities and morbidities lead to a concurrent pandemic of uncertainty in scientific evidence. Conflicting evidences are released on daily basis about the neonatal outcomes of COVID-19 positive mothers. The aim of this study was to use the relevant case reports and series to determine the percentage of newborns who test positive in COVID-19 positive mothers. Secondary outcomes included examining laboratory and placental abnormalities among fetus-mother pairs.Methods:Systematic review was performed on all studies reporting primary data on fetus-mother pairs with COVID-19. Data bases were searched for studies that met our inclusion and exclusion criteria.Results: Final screening revealed 66 studies, from which the primary data of 1787 mother-infant pairs was obtained. Only 2.8% of mother infant pairs were tested positive, and this finding is identical to percentages reported in former coronaviridae outbreaks. Whereas, 20% manifested with intrauterine hypoxia alongside placental abnormalities suggestive of heavy placental vaso-occlusive involvement. Conclusions: These findings suggest that while vertical transmission is unlikely, there appears to be an underlying risk of placental insufficiency due to the prothrombotic tendency observed in COVID-19 infection. Guidelines for proper prophylactic anticoagulation in COVID positive mothers need to be established.
Visual Variations between Pairs of SARS-CoV-2 Genomes on Integrated Density Matrix
Authors: Zhu Minghan , Zheng Jeffrey 
Published: September 2020

Abstract
This paper is the B2 module of the MAS. The quantification matrix is formed according to the four-base arrangement in the genome sequence. The differences in new coronavirus genome sequencing sequences in different samples were demonstrated by using the most concise methods. Using 4 primitive variable value measures, changes in the virus genome sequence base order conditions were determined. When two relatively large genomic sequences are slightly different, the integrated distribution of the difference calculation is subtly similar to the Bose-Einstein distribution, while the sum calculation shows a powerful distribution complexity. It can be formed under the macroscopic angle and can distinguish 16 combinations of supersymmetric structures. In view of the abundant transformation structure in this kind of transformation system, the detailed exploration remains to be followed by the systematic expansion of theory and medical application.
Age and gender distribution of COVID-19 infected cases in Italian population
Authors: Arisi Ivan , Mantuano Elide 
Published: September 2020

Abstract
Since the SARS-CoV-2 epidemic started, it became clear that the impact of the infection incidence and fatality rate were closely related to the population structure. Our analysis was devoted to the distribution of the infected cases in the Italian population stratified by age and sex in order to define the differences in gender impact of COVID-19 in each age class. Data on infected cases were extracted from the Italian EpiCentro (ISS) web site from March 12 to May 20, 2020. Data were pooled in ten years’ groups. Odds ratio (OR) men versus women was evaluated by the Fisher exact test. Logistic regression was used to investigate the combined effect of age and sex on infection incidence. Statistical analysis, performed by R-Bioconductor, highlights differences in age-dependent susceptibility to infection between men and women. In elderly class (50+ ) generally man result more infected than women, with the exception of the oldest women (90+). In age classes <50 OR was about 1.0, while an intriguing exception is the age group 20-29 in which the ratio was unbalanced in favour of men. This analysis supports a strong influence of biological sex and environmental factors related to age in COVID-19 infection by SARS-Cov-2.
Comparative Study of Pathogenic Viruses Carried on Pairs of Species
Authors: Zhang Xin , Pan Zhaoyu , Zheng Jeffrey 
Published: September 2020

Abstract
The new coronavirus was checked on December 12, 2019, and spread rapidly over time. It has become a public health event spreading around the world. Until this time, the source of the virus remains controversial. In this paper, a series of SARS-CoV-2 genomes were collected using the A1 module of the MAS for visualization. Pairs of genomes are compared under similarity relationships between SARS-CoV-2 and other deadly viruses carried by different species. Through the proposed method of variant construction, it provides important information to understand similarity properties among genomes. The comparison mechanism provides an efficient and fast similarity mode to compare with a whole genome at multiple levels of hierarchical measurements to provide variation information on internal correlation to a certain extent. Sample results are intuitively expressed through a list of 1D visual line charts for various distributions.