bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 infection among women in Israel, 2010-2018
Authors: Wagner Tali , Olshtain-Pops Karen , Wax Marina , Horwitz Olivia , Shirazi Rachel , Gozlan Yael , Volnowitz Hadar , Mendelson Ella , Levy Itzchak , Mor Orna
Published: August 2020

Introduction: Although women comprise 33% of the HIV-1-carriers in Israel, they have not previously been considered a risk group requiring special attention. Immigration waves from countries in Africa and in East Europe may have changed the local landscape of women diagnosed with HIV-1. Here, we aimed to assess viral and demographic characteristics of HIV-1-positive women identified in Israel between 2010 and 2018.Methods: All >16 year-old, HIV-1-infected women, diagnosed in Israel in 2010-2018, (n=763) registered in the National HIV reference laboratory were included in this cross-sectional study. Demographic and clinical characteristics were extracted from the database. Viral subtypes and transmitted drug resistance mutations (TDRM) were determined in 337 (44.2%) randomly selected samples collected from treatment-naive women. Results: Median age at diagnosis was 38 years. Most (73.3%) women were immigrants from the former Soviet Union (FSU) (41.2%, 314) or sub-Saharan Africa (SSA) (32.2%, 246) and carried subtype A (79.7%) or C (90.3%), respectively. Only 11.4% (87) were Israeli-born women. Over the years, the prevalence of women from SSA decreased while that of women from FSU increased significantly (p<0.001). The median CD4+ cell count was 263 cells/mm3, and higher (391 cells/mm3) in Israeli-born women. TDRM were identified in 10.4% of the tested samples; 1.8%, 3% and 7.1% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively. The prevalence of women with NNRTI TDRM significantly increased from 4.9% in 2010-2012 to 13.3% in 2016-2018. Israeli-born women had the highest prevalence (16.3%) of NNRTI TDRM (p=0.014). NRTI A62 (5.6%), NNRTI E138 and K103 (5.6% and 4.2%, respectively) were the most prominent mutated sites. Conclusions: Most HIV-1-positive women diagnosed in Israel in 2010-2018 were immigrants, with the relative ratio of FSU immigrants increasing in recent years. The high proportion of women diagnosed with resistance mutations, particularly, the yearly increase in the frequency of NNRTI mutations, support the national policy of resistance testing at baseline.
Admission fasting plasma glucose is associated with in-hospital outcomes in patients with acute coronary syndrome and diabetes: findings from the Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS) project
Authors: Ye Nan , Yang Lijiao , Wang Guoqin , Bian Weijing , Xu Fengbo , Ma Changsheng , Zhao Dong , Liu Jing , Hao Yongchen , Liu Jun , Yang Na , Cheng Hong
Published: August 2020

BackgroundThe discrepancy between glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in clinical practice may be related to factors such as acute stress, renal dysfunction, and anemia, and its relationship with in-hospital outcomes is uncertain. The aim of this study was to investigate the association between the type of discrepancy between HbA1c and FPG and in-hospital outcomes in patients with acute coronary syndrome (ACS) and diabetes.MethodsThe Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS) project is a national, hospital-based quality improvement project with an ongoing database. Patients with ACS, diabetes and complete HbA1c and FPG values at admission were included. The consistent group included patients with HbA1c < 6.5% and FPG < 7.0 mmol/L or HbA1c ≥ 6.5% and FPG ≥ 7.0 mmol/L. The discrepancy group included patients with HbA1c ≥ 6.5% and FPG < 7.0 mmol/L (increased HbA1c group) or HbA1c < 6.5% and FPG ≥ 7.0 mmol/L (increased FBG group).ResultsA total of 7,762 patients were included in this study. The numbers of patients in the consistent and discrepancy groups were 5,490 and 2,272 respectively. In the discrepancy group, increased HbA1c accounted for 77.5% of discrepancies, and increased FPG accounted for 22.5% of discrepancies. After adjusting for confounders, patients in the increased FPG group had a 1.6-fold increased risk of heart failure (OR, 1.62; 95% CI, 1.08-2.44), a 1.6-fold increased risk of composite cardiovascular death and heart failure (OR, 1.63; 95% CI, 1.09-2.43), and a 1.6-fold increased risk of composite major adverse cardiovascular and cerebrovascular events (MACCEs) and heart failure (OR, 1.56; 95% CI, 1.08-2.24) compared to patients in the increased HbA1c group.Conclusions Patients with an increased FPG but normal HbA1c had a higher risk of in-hospital adverse outcomes than those with increased HbA1c but normal FPG.This result may indicate that when HbA1c and FPG are inconsistent in patients with ACS and diabetes, the increased FPG that may be caused by stress hyperglycemia may have a more substantial adverse effect than increased HbA1c, which may be caused by chronic hyperglycemia. These high-risk patients should be given more attention and closer monitoring in clinical practice.
WITHDRAWN: A software tool for calculating the uncertainty of diagnostic accuracy measures
Authors: Chatzimichail Theodora , Hatjimihail Aristides T.
Published: August 2020

Background: Screening and diagnostic tests are used to classify people with and without a disease. Although diagnostic accuracy measures are used to evaluate the correctness of a classification in clinical research and practice, there has been limited research on their uncertainty. The objective for this work is to develop a tool for calculating the uncertainty of diagnostic accuracy measures, as diagnostic accuracy is fundamental to clinical decision-making.Results: For this reason, a freely available interactive program has been developed in Wolfram Language. The program provides six modules with nine submodules, for calculating and plotting the standard and expanded uncertainty and the resultant confidence intervals of various diagnostic accuracy measures of screening or diagnostic tests, which measure a normally distributed measurand, applied at a single point in time in non-diseased and diseased populations. This is done for differing population sample sizes, mean and standard deviation of the measurand, diagnostic threshold and standard measurement uncertainty of the test.The application of the program is illustrated with a case study of glucose measurements in diabetic and non-diabetic populations, that demonstrates the calculation of the uncertainty of diagnostic accuracy measures.Conclusion: The presented interactive program is user-friendly and can be used as a flexible educational and research tool in medical decision making, to calculate and explore the uncertainty of diagnostic accuracy measures.
Longitudinal changes in sports activity from pre-diagnosis to first five years post-diagnosis: a prospective Chinese breast cancer cohort study
Authors: Lei Yuanyuan , Ho Suzanne C. , Kwok Carol , Cheng Ashley , Cheung Ka Li , Lee Roselle , Yeo Winnie
Published: August 2020

Background: To compare change in level of physical activity between pre-and post- diagnosis of breast cancer in Chinese women.Methods: Based on an on-going prospective study consisting of 1462 Chinese women with early-stage breast cancer, a validated modified Chinese Baecke questionnaire was used to measure physical activity at baseline (12 months before cancer diagnosis), 18-, 36- and 60-months after diagnosis (over the previous 12 months before each interview).Results: The mean level of physical activity at post-diagnosis was 9.6 metabolic equivalent of task (MET)-hours/week, which was significantly higher than that at pre-diagnosis with mean level of 5.9 MET-hours/week ( P < 0.001). The mean levels of physical activity at 18-, 36- and 60-months follow-up were 9.9, 9.8 and 9.3 MET-hours/week, respectively. There was no significant difference between any two of the three follow-ups at post-diagnosis. The proportions of participant who met World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) recommendation before and after cancer diagnosis were both low, being 20.7% and 35.1%, respectively. Compared to pre-diagnosis, most of the patients improved or had no change on level of physical activity at post-diagnosis, with the respective proportion being 48.2% and 43.8%.Conclusions: Adherence to current lifestyle recommendation for cancer survivors, Chinese women with breast cancer significantly increased level of physical activity level after cancer diagnosis, and such improvement was sustained to five years post-diagnosis. The proportion of patients who met the exercise recommendation for cancer survivors was still low. Encouraging patients on the importance of durable high level of physical activity in breast cancer survivorship is warranted.
Comparison of BSGI , MRI, mammography, and ultrasound for the diagnosis of breast lesions and their correlations with specific molecular subtypes in Chinese women
Authors: Liu Hongbiao , Zhan Hongwei , Sun Da , Zhang Ying
Published: August 2020

Background: Breast cancer is a leading cause of cancer in females, and is the second leading cancer-related cause of death in this group. Early diagnosis is essential to breast cancer to be effectively treated, and ultrasound, mammography, and magnetic resonance imaging (MRI) represent three key technologies that are utilized for the diagnosis of breast lesions. Breast-specific gamma imaging (BSGI) is an approach to molecular breast imaging that allows for high-resolution radio-imaging that is not adversely impacted by breast tissue density. This study was therefore designed to assess the relative diagnostic efficacy of BSGI, MRI, mammography, and ultrasound in different molecular subtypes of breast cancer among Chinese women.Methods: Diagnostic findings from 390 patients that had undergone diagnosis and treatment in our breast surgery department were retrospectively reviewed. Patients had been diagnosed via BSGI, mammography, ultrasound, and MRI. The diagnostic efficacy of these different imaging modalities and their associated biological characteristics were compared in the present study.Results: A total of 229 of these 390 patients (58.7%) were diagnosed with malignant breast cancer, with the remaining 161 (41.3%) cases having been found to be benign. BSGI, MRI, mammography, and ultrasound yielded respective sensitivity values of 91.7%, 92.5%, 77.3%, and 82.1%, while the respective specificity values for these imaging modalities were 80.7%, 69.7%, 74.5%, and 70.8%. For lesions > 1 cm, BSGI offered a sensitivity of 92.5%. For mammographic breast density A, B, C, and D, BSGI offered a sensitivity of 93.3%, 94.0%, 91.5%, and 89.3%, respectively. BSGI also yielded a significantly higher lesion-to-normal lesion ratio (LNR) for malignant lesions relative to benign lesions (2.76±1.32 vs 1.46±0.49).Conclusions: These findings confirm that BSGI is highly sensitive and is superior to mammography in the detection and diagnosis of ductal carcinomas in situ (DCIS). Such diagnostic efficacy can be further improved by using BSGI as an auxiliary modality to mammography and ultrasound, potentially improving the reliability of breast lesion diagnosis, thereby ensuring that patients receive rapid and effective treatment without the risk of misdiagnosis or unnecessary surgical treatment.
COVID-Track: World and USA SARS-COV-2 Testing and COVID-19 Tracking
Authors: Zohner Ye Emma Mariam , Morris Jeffrey S
Published: August 2020

Background The COVID-19 pandemic has caused major health and socio-economic disruptions worldwide. Accurate investigation of emerging data is crucial to inform policy makers as they construct viral mitigation strategies. Complications such as variable testing rates and time lags in counting cases, hospitalizations and deaths make it challenging to accurately track and identify true infectious surges from available data, and requires a multi-modal approach that simultaneously considers testing, incidence, hospitalizations, and deaths. Although many websites and applications report a subset of these data, none of them provide graphical displays capable of comparing different states or countries on all these measures as well as various useful quantities derived from them. Here we introduce a freely available graphical application that allows the user to simultaneously assess time trends in these measures and compare various states or countries, equipping them with a tool to investigate the potential effects of the different mitigation strategies and timelines used by various jurisdictions. Findings COVID-TRACK is a Python based web-application that provides a platform for tracking testing, incidence, hospitalizations, and deaths related to COVID-19 along with various derived quantities. Our application makes the comparison across states or countries in the world easy to explore, with useful transformation options including per capita, log scale, and/or moving averages. We illustrate its use by assessing various viral trends in the USA and Europe. Conclusion The COVID-TRACK web-application is a user-friendly analytical tool to compare data and trends related to the COVID-19 pandemic across areas in the United States and worldwide. Our tracking tool provides a unique platform where trends can be monitored across geographical areas in the coming months to watch how the pandemic waxes and wanes throughout the summer and into a potential second wave in the fall.
Wear of Glass-ceramic-veneered Zirconia Posterior FPDS After 10 Years
Authors: Matta Ragai Edward , Motel Constantin , Kirchner Elena , Stelzer Simon , Adler Werner , Wichmann Manfred , Berger Lara
Published: August 2020

BackgroundThe abrasion behavior of various ceramics is rarely investigated, though it is relevant for the clinical success of such restorations. The aim of this in vivo study was to evaluate the wear of glass-ceramic-veneered zirconium oxide frameworks over a period of 10 years.MethodsThe abrasive behavior of the restorations was examined in a total of 15 patients after a period of 3, 5, and 10 years using plaster models, which were then subjected to a scanning process on the Atos II industrial scanner and digitized for three-dimensional evaluation of the abrasion by the corresponding software (ATOS Professional 7.6). The individual post-examination models were compared to the baseline model and deviations calculated in the sense of the largest, punctual loss of material in millimeters ("minimal distance"), the average abrasion in millimeters ("mean distance"), and the volume decrease in cubic millimeters ("integrated distance"). Statistical analyses were performed using the Wilcoxon sign rank test or mixed regression models. Multiple testing was considered by Benjamini-Hochberg correction. The significance level was set at 0.05.ResultsWe found steadily increasing wear of the ceramic. The average volume decrease was significant (P < 0.001) at 3 years and 10 years (-3.25 mm3 and − 8.11 mm3, respectively).ConclusionsDespite the increasing wear of the glass-ceramic-veneered zirconium oxide frameworks in this study, the use of this class of materials can be regarded as clinically acceptable.This study is registered in DRKS - German Clinical Trials Registerwith the Register number 00021743
The neutrophil-to-lymphocyte ratio determines clinical efficacy of corticosteroids therapy in patients with COVID-19
Authors: Cai Jingjing , Li Haomiao , Liu Ye-Mao , Zhang Changjiang , Lei Fang , Qin Juan-Juan , Zhou Feng , Song Xiaohui , Bai Liangjie , Zhou Jianghua , Zhao Yan-Ci , Zhu Lihua , Zhang Peng , Zhang Xin , Yang Juan , Ji Yan-Xiao , Zhao Guang-Nian , Lu Zhigang , Liu Liming , Mao Weiming , Liao Xiaofeng , Lu Haofeng , Wang Daihong , Xia Xigang , Huang Xiaodong , Wei Xiang , Xia Jiahong , Zhang Bing-Hong , Yuan Yufeng , Wang Yibin , Zhang Xiao-Jing , She Zhi-Gang , Li Hongliang
Published: August 2020

Preliminary results from the RECOVERY trial indicated that dexamethasone usage markedly reduced death rate in COVID-19 patients receiving invasive mechanical ventilation. However, the overall reduction for the entire patient cohort in that trial was much more modest, indicating highly variable effects of corticosteroid usage among COVID-19 patients. While steroid treatment is known to have both clinical efficacy and detrimental adverse-effects, defining a clinic parameter that could guide the beneficial corticosteroid usage for treating COVID-19 remains an elusive, urgent, and critical unmet need in COVID-19 therapy. Here, we undertook a multicentered retrospective study on a cohort of 12,862 confirmed COVID-19 cases from 21 hospitals in Hubei Province, China, including 3,254 received corticosteroid treatment and 9,608 received usual care without corticosteroid. We uncovered that the clinical benefits of corticosteroid use were closely associated with the neutrophil-to-lymphocyte ratio (NLR) measured at admission. Among participants with NLR > 6.12 at admission, corticosteroid treatment was significantly associated with a lower risk of 60-day all-cause mortality of COVID-19 based on both Cox model with time-varying exposure and Marginal Structural Model. However, in patients with NLR ≤ 6.12 at admission, corticosteroid treatment was no longer associated with reduced risk of all-cause death, but rather with increased risks of severe adverse effects, particularly in hyperglycemia and infection. In diabetic patients with COVID-19, corticosteroid treatment was associated with increased glycemia, but not with a higher risk of 60-day mortality. Therefore, our study has uncovered NLR as a clinical indicator to stratify COVID-19 patients in their response to corticosteroid therapy. This finding may assist clinical evaluation and future randomized controlled trials to establish proper guidelines for corticosteroid therapy in COVID-19 patients.
Clinical Option of Pemetrexed-Based Versus Paclitaxel-Based First-Line Chemotherapeutic Regimens in Combination With Bevacizumab for Advanced Non-Squamous Non-Small-Cell Lung Cancer and Optimal Maintenance Therapy: Evidence From a Meta-Analysis of Randomized Control Trials
Authors: Huang Le-Tian , Cao Rui , Wang Yan-Ru , Sun Li , Zhang Xiang-Yan , Guo Yi-Jia , Zhao Jian-Zhu , Zhang Shu-Ling , Jing Wei , Song Jun , Han Cheng-Bo , Ma Jie-tao
Published: August 2020

Background: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. Methods: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP±B) and paclitaxel-carboplatin with bevacizumab (PC+B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem+B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events.Results: Data of 3,139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP±B and PC+B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP±B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC+B (all P<0.05). PP±B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC+B (all P<0.001). The other three RCTs were included in an analysis that compared Pem+B and B as a maintenance treatment. Compared with B, Pem+B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P<0.001).Conclusion: Although the first-line PP+B regimen had longer PFS and PFSR1y than the PC+B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.
A novel modification of the Endorectal Advancement Flap for complex anal fistulas: surgical technique and outcomes
Authors: Al-Turaihi Hassan , Elizabeth Blears , Kavin Sugumar , Maya Deshmukh , Ganesh Deshmukh
Published: August 2020

Background Fistula-in-ano is a common problem encountered by surgeons which can be classified as either simple or complex. Complex fistulas (CF) cause higher morbidity and are much more challenging to treat. Although numerous treatment options are available for CF, none are proven to be 100% effective. The endorectal advancement flap (EAF) procedure was developed as an alternative to conventional surgical treatments for CF. Herein, we describe a novel modification of the EAF procedure along with surgical outcomes in terms of recurrence, fecal incontinence and factors associated with flap failure. Methods A retrospective review of patients with complex fistula-in-ano who underwent EAF between 2004-2019 was done. The conventional EAF procedure was modified by performing transverse imbrication of the internal sphincter over the internal fistula opening. The incidence of post-operative recurrence and fecal incontinence were calculated from chart documentation at the last available date of follow-up. Also, the association between various clinical and demographic factors and post-operative flap failure were calculated using Chi-squared test and student’s t-test or Mann-Whitney U test with statistical significance at alpha <0.05. Results With a median follow-up of 6.6 months (range: 1.6-84.5 months), 99 patients with CFs underwent a modified EAF. Of these, 93% (92/99) had a successful procedure, 7% (7/99) experienced recurrence and 3% (3/99) experienced postoperative fecal incontinence. Systemic steroid or immunomodulatory therapy use (p=0.001) and patients with diagnosed inflammatory bowel disease (p<0.0001) were associated with increased rate of flap failure.Conclusion EAF with transverse imbrication of the internal opening using interrupted, absorbable suture is an effective technique to treat complex or recurrent anal fistulas. It is associated with a low risk of recurrence (7%) and fecal incontinence (3%) and a valid treatment option for complex fistula-in-ano.
Seroprevalence of Mycobacterium avium subsp. paratuberculosis in Dairy Cattle in Khartoum State, Sudan.
Authors: Elmagzoub Wisal Abdalrahman , Adam Nabawia Mohamed , Idris Sanaa Mohamed , Mukhtar Mohamed Elwaseela , Abdelaziz Sanaa , Okuni Julius Boniface , Ojok Lonzy , Wahed Ahmed Abd El , Eltayeb ElSagad , Gameel Ahmed Abdelrahim , Eltom Kamal Hassan
Published: August 2020

Background: Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic wasting disease of mainly domestic and wild ruminants (mammals). It occurs worldwide causing significant economic losses through decreased productivity, low fertility, increased cull rates and mortality. It is an OIE listed disease of concern to trade in animals. The aim of this study was to investigate the current prevalence of MAP infection in cattle in Khartoum State.Results: The overall apparent prevalence of MAP infection was found to be 6.3% and 18.9% (95% CL) at animal and herd levels, respectively. All seropositive animals were cross-bred females of good body condition; most of them (>90%) were >3 years old and >50% were from medium sized herds in Omdurman. No significant association (X2 >0.05) was found between seropositivity and animal herd data.Conclusion: The prevalence of MAP infection in Khartoum State is still low to medium compared to other parts of the world, but it is comparable to that reported from other African countries. Further studies with the view of designing wide national surveys in domestic ruminants and camels in other states of the country are needed for establishing control programmes.
Poor Health-related Physical Fitness Performance Increases the Overweight and Obesity Risk in Elderly People From Taiwan
Authors: Lee Po-Fu , Ho Chien-Chang , Chen Hui-Ling , Tseng Ching-Yu , Hsieh Xin-Yu , Chiu Chih Hui
Published: August 2020

Background
The purpose of the present study was to investigate the associations between health-related physical fitness performance and overweight/obesity risk among Taiwanese healthy older adults.
Methods
A secondary dataset from the nationwide survey with 21,630 data was applied in this study. Demographic characteristics, life habits, perceived health status, anthropometric assessments, and health-related physical fitness measurements from this dataset were analyzed using the chi-square test, one-way analysis of variance, and logistic regression analysis.
Results
The results indicated that overweight and obesity significantly reduced health-related physical fitness performance in the Taiwanese older adult population. In particular, the upper extremity muscular endurance scores of older adults with poor activity and physical fitness scores revealed obesity as a critical indicator of health-related physical fitness performance.
Conclusions
Future studies can use muscle quality or body fat classification to predict obesity in older adults, which could more precisely portray the relationship between obesity and health-related physical fitness performance.
RASMA: A Reverse Search Algorithm for Mining Frequent Subgraphs
Authors: Salem Saeed , Alokshiya Mohammed , Hasan Mohammad Al
Published: August 2020

Background: Mining frequent co-expression networks enables the discovery of interesting network motifs that elucidate important interactions among genes. Such interaction subnetworks have been shown to enhance the discovery of biological modules and subnetwork signatures for gene expression and disease classification. Results: We propose a reverse search algorithm for mining frequent and maximal subgraphs over a collection of graphs. We develop an approach for enumerating connected edge-induced subgraphs of an undirected graph by using a reverse-search algorithm, and then use this enumeration strategy for mining all maximal frequent subgraphs. To overcome the computationally prohibitive task of enumerating all frequent subgraphs while mining for maximal subgraphs, the proposed algorithm employs several pruning strategies, which substantially improve its overall runtime performance. Experimental results show that on large gene coexpression networks, the proposed algorithm efficiently mines biologically relevant maximal frequent subgraphs. Conclusion: Extracting recurrent gene coexpression subnetworks from multiple gene expression experiments enables the discovery of functional modules and subnetwork biomarkers. We have proposed a reverse search algorithm for mining maximal frequent subnetworks. Enrichment analysis of the extracted maximal frequent subnetworks reveals that subnetworks that are more frequent are more likely to be enriched with biological ontologies.
A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system
Authors: Moss Alison , Robbins Shaina , Achanta Sirisha , Kuttippurathu Lakshmi , Turick Scott , Nieves Sean , Hanna Peter , Smith Elizabeth , Hoover Donald , Chen Jin , Cheng Zixi (Jack) , Ardell Jeffrey , Shivkumar Kalyanam , Schwaber James , Vadigepalli Rajanikanth
Published: August 2020

We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion - the right atrial ganglionic plexus (RAGP) that is a critical mediator of vagal control of the sinoatrial node (SAN) activity. We developed a 3D representation of RAGP with extensive mapping of neurons and used neuronal tracing to identify the spatial distribution of the subset of neurons that project to the SAN. RNAseq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to CNS neuronal subtypes. High-throughput qPCR of hundreds of laser capture microdissected single neurons led to a surprising finding that cholinergic and catecholaminergic neuronal markers Th and Chat were correlated, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. Interestingly, no single gene or module was an exclusive marker of RAGP neuronal connectivity to SAN. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP, informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.
Lung nodules and IgG4 related disease: a single-center based experience
Authors: Xie Yan , Xiong Anji , Marion Tony , Liu Yi
Published: August 2020

Background: This study was undertaken in an attempt to characterize the frequency and clinical features of lung nodules in IgG4 related disease (IgG4-RD) patients as an insight for help with the diagnosis of lung nodules.Methods: A retrospective study was carried out in West China Hospital, Sichuan University from January 2012 to December 2018, 89 patients with definite IgG4-RD were enrolled.Results: Fifty of 89 patients with definite IgG4-RD had radiologically confirmed lung nodules, 6 of whom were diagnosed with definite IgG4 related lung disease. Lung nodules detected in more than 40 patients were small and solid, always with regular margins. Multiple (41/50) and bilateral (34/50) distributions was also a major characteristic of these lung nodules. Lobulation and speculation were simultaneously detected in 3 patients, including 2 patients combined with pleural indentation. Calcification of nodules was detected in only one patient. Thirty-seven patients also had additional radiological abnormalities of lungs, including ground-glass opacity (21/50), thickening of pleura (9/50), thickening of interlobular septa (4/50), thickening of bronchial wall (3/50), pleural effusion (4/50), mass (3/50), interstitial changes (5/50), and mediastinal or hilar lymphadenopathy (32/50). Most patients (44/50) were treated with glucocorticoids alone or combined with immunosuppressive agents. Sixteen patients received a re-examination by chest computed tomography (CT) scan after treatment, 10 of whom showed a decrease in the size and/or the number of nodules.Conclusions: The incidence of lung nodules in IgG4-RD patients can be high. For an IgG4-RD patient with lung nodules, the possibility that the lung nodules related to IgG4-RLD is high. It is hard to differentiate IgG4 related lung nodules from other lung diseases, in particular, lung cancer. Radiological characteristics and positive responses to glucocorticoids and immunosuppressive agents can help with the differential diagnosis. For these patients, regular follow-up is also important.
Mechanistic modeling of the SARS-CoV-2 disease map
Authors: Rian Kinza , Esteban-Medina Marina , Hidalgo Marta R , Çubuk Cankut , Falco Matias M , Loucera Carlos , Gunyel Devrim , Ostaszewski Marek , Peña-Chilet María , Dopazo Joaquin
Published: August 2020

Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inferred from gene expression experiments. Moreover, the effect of potential interventions, such as knock-downs, or drug effects (currently the system models the effect of more than 8000 DrugBank drugs) can be studied. This freely available tool not only provides an unprecedentedly detailed view of the mechanisms of viral invasion and the consequences in the cell but has also the potential of becoming an invaluable asset in the search for efficient antiviral treatments.
Prevalence and predictors of child labour among junior public secondary school students in Enugu, Nigeria: a cross-sectional study
Authors: Enebe Joseph Tochukwu , Enebe Nympha Onyinye , Enebe Joseph Tochukwu , Agunwa Chuka Chike , Ossai Edmund Ndudi , Ezeoke Uchechukwu Enuma , Idoko Arthur Chinedu , Mbachu Chinyere Ojiugo
Published: August 2020

Background
Millions of children have been identified globally to be involved in child labour with low-income countries being mostly hit. This study was aimed at assessing child labour and its predictors among public secondary school students in Enugu metropolis.
Methods
The study was a descriptive cross-sectional study of 332 junior secondary school students attending public secondary schools in Enugu metropolis, Nigeria. A structured interviewer-administered questionnaire was used for data collection and analyses were done using SPSS version 23 and STATA Software. The level of statistical significance was set at 5% p-value.
Results
The prevalence of overall child labour among the respondents was high (71.7%) likewise its different categories: domestic (52.1%) and economic (34.0%) child labour. About 35.2% of the respondents worked under hazardous conditions while 8% were forced to work. Approximately 65% (236) of the respondents who had heard about child labour perceived it as wrong. They mainly worked to render financial assistance to their parents. Class of study (AOR = 2.208 (95% CI: 1.199–4.066) and weekly income earned (AOR = 0.316 (95% CI: 0.176–0.567) predicted child labour among the respondents.
Conclusion
The prevalence of child labour among public secondary schools in Enugu was high and the predictors were the class of the respondents and the weekly income they made. This may imply that child labour in Enugu was driven by poverty as respondents who earned higher were more involved in child labour thereby calling for concerted economic and social reforms to reduce this menace.
Accurate and Objective Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Disease Severity with a Wearable Sensor
Authors: Palombo Turner , Campos Andrea , Vernon Suzanne D. , Roundy Shad
Published: August 2020

Background Approximately 2.5 million people in the U.S. suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This disease negatively impacts patients’ ability to function, often resulting in difficulty maintaining employment, sustaining financial independence, engaging socially with others, and in particularly severe cases, consistently and adequately performing activities of daily living. The focus of this research was to develop a sensor-based method to measure upright activity defined as time with feet on the floor and referred to as UpTime, as an indicator of ME/CFS disease severity.Methods A commercially available inertial measurement unit (IMU), the Shimmer, was selected for this research. A Kalman filter was used to convert IMU data collected by the Shimmer to angle estimates. Angle estimate accuracy was confirmed by comparison to a motion capture system. Leg angle estimates were then converted to personalized daily UpTime scores using a critical angle of 39º from vertical to differentiate between upright (feet on the floor) and not upright. A six-day, case-control study with 15 subjects (five healthy controls, five moderate-level ME/CFS, and five severe-level ME/CFS) was conducted to determine the utility of UpTime for assessing disease severity.Results UpTime was found to be a significant measure of ME/CFS disease severity. Severely ill ME/CFS patients spend less than 20% of each day with feet on the floor. Moderately ill ME/CFS patients spend between 20–30% of each day with feet on the floor. Healthy controls have greater than 30% UpTime. IMU-measured UpTime was more precise than self-reported hours of upright activity which were over-estimated by patients.Conclusions UpTime is an accurate and objective measure of upright activity, a measure that can be used to assess disease severity in ME/CFS patients. Due to its ability to accurately monitor upright activity, UpTime can also be used as a reliable endpoint for evaluating ME/CFS treatment efficacy. Future studies with larger samples and extended data collection periods are required to fully confirm the use of UpTime as a measure of disease severity in ME/CFS. With the added perspective of large-scale studies, this sensor-based platform could provide a recovery path for individuals struggling with ME/CFS.
Comparative Effectiveness of Dulaglutide Versus Iiraglutide in Asian type 2 Diabetes Patients: A Multi-Institutional Cohort Study and Meta-Analysis
Authors: Chang Kai-Cheng , Shao Shih-Chieh , Kuo Shihchen , Yang Chen-Yi , Chen Hui-Yu , Chan Yuk-Ying , Ou Huang-tz
Published: August 2020

BackgroundHead-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. MethodsWe conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016-2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every three months in the one-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. ResultsA total of 1,512 subjects receiving dulaglutide and 1,513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: -1.06%, p<0.001; liraglutide: -0.83%, p<0.001), with a significant between-group difference (-0.23%, 95% confidence interval: -0.38 to -0.08%, p<0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: -1.14 kg, -3.08 U/L and -2.08 ml/min/1.73 m2, p<0.01; liraglutide: -1.64 kg, -3.65 U/L and -2.33 ml/min/1.73 m2, p<0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (-2.47 mmHg, p<0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. ConclusionsIn real-world T2D patients, dulaglutide versus liraglutide yielded better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.
Treatment Strategies for Nonunion After Intramedullary Nailing for Femoral Fracture: Experiences of Fifty Nonunion Patients
Authors: Yu Guang-Shu , Xu Yang-Kai , Lin Yan-Bin , Zhuang Yan , Xiong Sheng-Ren , Xiong Guo-Sheng
Published: August 2020

Background: Femoral nonunion is mainly caused by factors such as instability of the fracture end, insufficient blood supply, or infection. However, these factors are mainly related to the different fracture types and inappropriate treatment plans. It is important to analyze the etiology of femoral nonunion and use a simple and effective treatment method to resolve it. The purpose of this study was to divide femoral nonunion into different types and give corresponding treatment strategies.Methods: We retrospectively evaluated 50 patients with femoral nonunion. Patients were divided into six groups and each group was treated with a different strategy. All patients were followed up clinically and radiologically every month until fracture healing.Results: All 50 patients were followed up with an average follow-up time of 17.44 ± 5.48 months. Based on the type of primary femoral fracture and the factors causing nonunion, we divided the femoral nonunion into six types. These included Type I: nonunion caused by instability of simple fracture (AO classification 32-A); Type II: nonunion caused by stress shielding at fracture ends of a simple fracture (AO/OTA classification 32-A); Type III: nonunion in femoral fracture with third fragment (AO/OTA classification 32-B); Type IV: nonunion in femoral fracture with segmental femoral fracture (AO/OTA classification 32-C2); Type V: nonunion in comminuted femoral fracture (AO/OTA classification 32-C3); and Type VI: nonunion caused by infection. Based on these classifications, the following methods are used to treat femoral nonunion. Type I femoral nonunion will achieve fracture healing by blocking screws, exchanging intramedullary nails, or adding plates. Type II femoral nonunion can be addressed through dynamitization or bone graft (possibly in combination with plate fixation) to achieve fracture healing. Type III femoral nonunion requires a treatment plan of bone graft or bone graft combined with plate fixation. The treatment plan for Type IV femoral nonunion is to add a plate, and autogenous bone graft if necessary. Type V femoral nonunion treatment is bone graft combined with plate fixation, or external fixation with subsequent bone segment transport or lengthening. Type VI requires placement of antibiotic bone cement or external fixation added to fix the fracture end.Conclusions: There are several factors associated with failure of femoral fracture treatments by intramedullary nailing. We need to carefully analyze the causes of fracture treatment failure. Our six classifications and corresponding treatment strategies resulted in satisfactory clinical outcomes.
Molecular Interaction of Cytotoxic Anticancer Analogues as Inhibitors of β-tubulin Protein Against UACC-62 Melanoma Cell
Authors: Chen Kuan-Chung , Wu Chi-Rei , Lien Jin-Cherng
Published: August 2020

Background
In previous research, a series of cytotoxic anticancer analogues related to 2-acylamino-1,4-naphthoquinone derivatives has been demonstrated. As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug.
Methods
This study performed molecular docking simulation, pharmacophore model, comparative force field analysis model, and comparative similarity indices analysis model to investigate the relationship between inhibitory activities and the properties of compounds, in order to further progress the development of cytotoxic anticancer analogues.
Results
These compounds have common H-bond interactions with key residues Lys254 and Lys352, but compounds with large R2 substituent have different docking poses than compounds with small R2 substituent. Some of derivatives such as compound 18 formed the H-bonds with residue Lys254 using the oxygen atoms in R1 substituent and formed π-cation interactions with residue Lys352 using phenyl moiety of 1,4-naphthoquinone. The R1 substituent of these compounds preferred to have disfavored hydrophobic fields and favorable space toward the direction of residue Asn258, while the R2 substituent of these compounds preferred to have about 2–3 carbon chain length hydrophobic substituent toward the direction of residues Ala316 and Lys352.
Conclusion
These results offer some beneficial advices for further study in anticancer drug development process.
Maternal mortality following thromboembolism; Incidences and prophylaxis strategies
Authors: Shirazi Mahboobeh , Sahebdel Behrokh , Torkzaban Mahnoosh , Feyzabad Elham , ghaemi marjan
Published: August 2020

Background: Thromboembolism is one of the main causes of maternal mortality, which can be prevented in many cases. The present study was designed to investigate the incidence and prophylaxis strategies for maternal mortality following thromboembolism.Methods: In this case series study, the data of the mortality cases were extracted according to the ethical and security standards of the Ministry of Health of the country. The thromboembolism risk factors measured and scored using a questionnaire entitled "the evaluation of risk factors for maternal mortality following thromboembolism during pregnancy, labor, or post-partum".Results: The maternal mortality rate was 16 per 100,000 live births. Among 297 mortality cases, 27 (9%) death were due to thromboembolism. The mean gestational age was 32.5 weeks. Dyspnea (88.8%) and tachycardia (18.5%) were found as common clinical manifestations in these patients. Sixteen cases (59.3%) did not get heparin, 6 (22.2%) received single dose and 5 (18.5%) received two doses and more. In these 11 cases, 5 (45%) patients received heparin before surgery, 1 after surgery, and 5 before and after surgery. Twenty cases deceased in the first hours after delivery and the rest after 2 to 12 days. The average score of risk for thromboembolism based on Royal College of Obstetricians & Gynecologist (RCOG) guideline was 4.6.Conclusion: It seems that one of the most important cause of maternal mortality in this study was the lack of recognition of high-risk patients and the lack of prescription for prophylaxis with heparin and this clearly explains the need for accurate screening of high-risk mothers, designing a standard form and the care and treatment of these patients.
Recommendation for Cranial Upper Border of Level Ⅱb in Clinical Target Volumes (CTV) for Nasopharyngeal Carcinoma
Authors: Wang Lijun , Huang Shengfu , Zhang Lanfang , He Xia , Liu Yatian
Published: August 2020

Purpose: To recommend the cranial side of level Ⅱb in clinical target volumes (CTV) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, to help reach a consensus on contouring level Ⅱb in CTV.Methods: From 2012 to 2016, 331 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. According to the AJCC 8th staging system of NPC, there were 15 patients with stage Ⅰ, 76 stage Ⅱ, 103 stage Ⅲ, and 137 stage Ⅳ. Distribution of cervical lymph nodes in NPC was assessed based on imaging results. Comparison of the safety and the parotid dose parameters between patients with or without a reduction in the range ofⅡb was taken by SPSS 25.0 and R 2.14.2 software.Results: Metastasis rates of the most common diseased lymph nodes, lateral retropharyngeal lymph node andⅡb lymph node, were 82.8% and 64.0%, respectively. Among patients with levelⅡb involvement, the upper borders of metastatic nodes in 13.7% of cases were beyond the caudal edge of C1. The D50 and V26 values for parotid glands were significantly reduced after modified the upper bound of level Ⅱb in CTV (P = 0. 000).Conclusions: The upper bound of level IIb，in principle，should reach the lateral skull base during the delineation of the cervical CTV for NPC. To protect the parotid glands, however, individualized reduction in the upper bound of level IIb is recommended for patients who meet the formulated standard.