bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of continuous epidural infusion with epidural electric stimulation compared to that of conventional continuous epidural infusion for acute herpes zoster management: A retrospective study﻿
Authors: Lee Chung Hun , Choi Sang Sik , Lee Mi Kyoung , Lee Yeon Joo , Park Jong Sun
Published: January 2020

Background: Continuous epidural infusions are commonly used in clinical settings to reduce the likelihood of transition to postherpetic neuralgia via pain control. The purpose of this study was to compare the efficacy of conventional continuous epidural infusion to that of continuous epidural infusion in which the catheter is guided by electric stimulation to areas with neurological damage for the treatment of zoster-related pain and prevention of postherpetic neuralgia.Methods: We analyzed the medical records of 114 patients in this study. The patients were divided into two groups: contrast (conventional continuous epidural infusion) and stimulation (continuous epidural infusion with epidural electric stimulation). In the contrast group, the position of the epidural catheter was confirmed using contrast medium alone, whereas in the stimulation group, the site of herpes zoster infection was identified through electric stimulation using a guidewire in the catheter. Clinical efficacy was assessed using a numerical rating scale (pain score) up to 6 months after the procedures. We compared the percentage of patients who showed complete remission (pain score less than 2 and no further medication) in each group. We also investigated whether the patients required additional interventional treatment due to insufficient pain control during the 6-month follow-up period after each procedure.Results: After adjusting for confounding variables, the pain score was significantly lower in the stimulation group than in the contrast group for 6 months after the procedure. After adjustment, the odds of complete remission were 1.9-times higher in the stimulation group than in the contrast group (95% confidence interval [CI]: 0.81-4.44, P = 0.14). Patients in the contrast group were significantly more likely to require other interventions within 6 months of the procedure than patients in the stimulation group (odds ratio: 3.62, 95% CI: 1.17-11.19, P = 0.03).Conclusion: Epidural drug administration to specific spinal segments using electric stimulation catheters may be more helpful than conventional continuous epidural infusion for improving pain and preventing postherpetic neuralgia in the acute phase of herpes zoster.
Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma
Authors: Noh Byeong-Joo , Kwak Jae Young , Eom Dae-Woon
Published: January 2020

Background

Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.Methods

Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and microsatellite instability (MSI) were performed and evaluated.Results

Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with MSI status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.Conclusions

TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.
Comparative analysis of somatic variant calling on matched FF and FFPE WGS samples
Authors: Brienen Louise de Schaetzen van , Larmuseau Maarten , Eecken Kim Van der , De Ryck Frederic , Robbe Pauline , Schuh Anna , Fostier Jan , Ost Piet , Marchal Kathleen
Published: January 2020

Background. Research grade Fresh Frozen (FF) DNA material is not yet routinely collected in clinical practice. Many hospitals, however, collect and store Formalin Fixed Paraffin Embedded (FFPE) tumor samples. Consequently, the sample size of whole genome cancer cohort studies could be increased tremendously by including FFPE samples, although the presence of artefacts might obfuscate the variant calling. To assess whether FFPE material can be used for cohort studies, we performed an in-depth comparison of somatic SNVs called on matching FF and FFPE Whole Genome Sequence (WGS) samples extracted from the same tumor.
Results. We first compared the calls between an FF and an FFPE from a metastatic prostate tumor, showing that on average 50% of the calls in the FF are recovered in the FFPE sample, with notable differences between variant callers. Combining the variants of the different callers using a simple heuristic increases both the precision and the sensitivity of the variant calling. Validating the heuristic on nine additional matched FF-FFPE samples, resulted in an average F1-score of 0.58 and an outperformance of any of the individual callers. In addition, we could show that part of the discrepancy between the FF and the FFPE samples can be attributed to intra-tumor heterogeneity (ITH).
Conclusion. This study illustrates that when using the correct variant calling strategy, the majority of clonal SNVs can be recovered in an FFPE sample with high precision and sensitivity. These results suggest that somatic variants derived from WGS of FFPE material can be used in cohort studies.
Decomposing the educational inequalities in the factors associated with severe acute malnutrition among under-five children in Low- and Middle-Income Countries
Authors: Fagbamigbe Adeniyi Francis , Kandala Ngianga- Bakwin , Uthman Olalekan
Published: January 2020

Background: Low- and Middle-Income Countries (LMIC) have remained plagued with the burden of severe acute malnutrition (SAM). The decomposition of the educational inequalities in SAM across individual, neighbourhood and national level characteristics in LMIC have not been explored. This study aims to decompose educational-related inequalities in the development of SAM among under-five children in LMIC and identify the risk factors that contribute to the inequalities. Methods: We pooled successive secondary data from the Demographic and Health Survey (DHS) conducted between 2010 and 2018 in 51 LMIC. We analysed data of 532,680 under-five children nested within 55,823 neighbourhoods. Severe acute malnutrition was the outcome variable while the literacy status of mothers was the main exposure variable. The explanatory variables cut across the individual-, household and neighbourhood-level factors of the mother-child pair. Oaxaca-Blinder decomposition method was used at p=0.05. Results: Mothers with no formal education ranged from 0.1 % in Armenia and Kyrgyz to as much as 86.1 % in Niger. The overall prevalence of SAM in the group of children whose mothers had no education was 5.8 % compared with 4.2 % among those whose mothers were educated, this varied within each country. Fourteen countries (Cameroon(p=0.000), Chad(p=0.000), Comoro(p=0.047), Burkina Faso(p=0.000), Ethiopia(p=0.000), India(p=0.000), Kenya(p=0.000), Mozambique(p=0.012), Namibia(p=0.001), Nigeria(p=0.000), Pakistan(p=0.000), Senegal(p=0.003), Togo(p=0.013), and Timor Leste(p=0.000) had statistically significant pro-illiterate inequality while no country showed statistically significant pro-literate inequality. We found significant differences in SAM prevalence across child’s age(p=0.000), child’s sex(p=0.000), maternal age(p=0.001), household wealth quintile(p=0.001), mother’s access to media(p=0.001), birth weight(p=0.000) and neighbourhood socioeconomic status disadvantage(p=0.000). On the average, neighbourhood socioeconomic status disadvantage, location of residence were the most important factors in most countries. Other contributors to the explanation of educational inequalities are birth weight, maternal age and toilet type. Conclusions: SAM is prevalent in most LMIC with wide educational inequalities. Educational inequalities in SAM was explained by individual, household and community-level factors. Promotion of women education should be strengthened as better education among women will close the gaps and reduce the burden of SAM generally. We recommend further studies of other determinate causes of inequalities in severe acute malnutrition in LMIC.
Associations between maternal BMI, breastfeeding practices and infant anthropometric status in Colombia; secondary analysis of ENSIN 2010.
Authors: Aldana-Parra Fanny , Olaya Gilma , Fewtrell Mary
Published: January 2020

• Background: Maternal malnutrition and infant feeding mode impact short and long term infant and child morbidity and mortality. The period of lactation may provide an opportunity to modulate the risk of disease later in life. Our aim was to estimate the effect of maternal body mass index (BMI) and infant feeding mode, particularly breastfeeding practices, on the anthropometric status of children under two years in Colombia.
Experiences, views and needs of first-time fathers in pregnancy related care: a qualitative study in south-east Nigeria.
Authors: Onyeze-Joe Chiemeka , Godin Isabelle
Published: January 2020

Background Given the relevance of paternal involvement in maternal care, there is a need to prepare first-time fathers to participate in pregnancy and childbirth actively. This study explores the experiences and needs of first-time fathers and the influence of these on their involvement during pregnancy and childbirth in Nigeria. Methods A descriptive qualitative study was conducted. Semi-structured interviews with 50 men recruited from rural and urban workplaces, hospitals, and markets, generated data used to explore the experiences, views and needs of first-time fathers’ in pregnancy-related care in south-east Nigeria. All data were transcribed and analysed using thematic analysis. Results Six major themes were identified: gender roles, antenatal involvement, care costs and delivery choices, need to be informed, dealing with emotions, and dealing with the delivery day. A key finding was that inexperience, cultural beliefs and perceptions of gender norms greatly influenced the support provided by first-time fathers to their spouses, and the support they received from their social support networks. Two primary needs were identified: need to be informed and the need to know about the cost of care in health settings. First-time fathers acknowledged the role of information on their decision making and final choices. Conclusion Findings reveal the influence of gender norms, beliefs, and social support on first-time fathers’ involvement in pregnancy and childbirth. This study also highlights the urgent need to provide informational support for first-time fathers and presents insights into what hospitals can do to achieve this need. Keywords: male involvement, first-time fathers, pregnancy, qualitative, Nigeria
Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites
Authors: Cheng Jintao , Cao Fei , Chen Xinai , Li Yongquan , Mao Xuming
Published: January 2020

Background: Endophytic fungi can produce many active secondary metabolites, which are important resources of natural medicines. However, there is currently little understanding of endophytic fungi at the omics levels. Calcarisporium arbuscula, an endophytic fungus from the healthy fruit of Russulaceae, can produce a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic bioactivities. Comprehensive survey of the endophytic fungi genome and transcriptome will help to understand their capacity to biosynthesize secondary metabolites and lay the foundation for the development of these precious resources.Results: In this study，we reported the high-quality genome sequence of a strain C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, relatively larger than other typical filamentous fungi, and comprises 10,001 predictable genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover, 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for mycotoxins aurovertins. In addition, several gene clusters were predicted to produce various mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown possibly involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assay showed that only the expression of aurovertin gene cluster is much stronger than the housekeeping genes under laboratory conditions, consistent with that aurovertins are the predominant metabolites. The gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than the housekeeping genes, which might partially explain poor production of other secondary metabolites in this fungus.Conclusions: Our omics data along with bioinformatics analysis indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce profound secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities.
Does Xpert MTB/RIF Assay Give Rifampicin Resistance Results Without Identified Mutation? Review of Cases from Addis Ababa, Ethiopia.
Authors: Alemu Ayinalem , Tadesse Mengistu , Seid Getachew , Mollalign Helina , Eshetu Kirubel , Sinshaw Waganeh , Abebaw Yeshiwork , Amare Misikir , Dagne Biniyam , Diriba Getu , Yenew Bazezew , Getu Melak , Zerihun Betselot
Published: January 2020

Background: Xpert® MTB/RIF assay is currently used in Ethiopia for the rapid diagnosis of Mycobacterium tuberculosis (MTB) and mutations that confer Rifampicin resistance. Rifampicin resistance is determined based on any mutation in the 81 bp of rpoB gene using five overlapping probes represented as Probe A (codons 507–511), Probe B (codons 512–518), Probe C (codons 518–523), Probe D (codons 523–529) and Probe E (codons 529–533). In this review, we assessed the frequency of missed probe types for Rifampicin Resistance results. Methods: Data were reviewed from specimens received and tested using Xpert® MTB/RIF assay at Ethiopian National Tuberculosis Reference Laboratory, in Addis Ababa from 15 July 2016 to 31 December 2018 retrospectively. All archived data were reviewed carefully to describe missed probe types and the quantity of DNA in the sample. Results: A total of 100 specimens were reported as MTB Detected Rifampicin Resistance Detected by Xpert® MTB/RIF assay. More than half (55%) of these results were reported from male patients. The median age was 28.0 years (5 months to 88 years). Majorities (62%) of the cases were detected from sputum. Among the total of 38 extrapulmonary samples, lymph node aspirates were accounted for 50% (19/38). The most common mutations (81.0%) were found in the Probe E region followed by Probe D (10.0%), and Probe B (3.0%). Mutations in Probe A and Probe C regions were not observed. However, six (6.0%) Rifampicin resistance cases were found without any missed probe type. The delta Ct max is ≥4.3. No specimen yielded Rifampicin resistance associated with more than one probe failure or mutation combinations. Conclusion: Mutations associated with Probe E (codons 529–533) region were identified as the commonest rpoB gene mutations. The Rifampicin resistance results found without any identified missing probe needs further study. The lower DNA amount was observed in extrapulmonary specimens compared with sputum. Keywords: Rifampicin-resistance, Molecular Beacon, DNA probes, Xpert® MTB/RIF Assay
Phylogeny of teleost connexins reveals highly inconsistent intra- and interspecies use of nomenclature and misassemblies in recent teleost chromosome assemblies
Authors: Mikalsen Svein Ole , Tausen Marni , Kongsstovu Sunnvør í
Published: January 2020

Background: Based on an initial collecting of database sequences from the gap junction protein gene family (also called connexin genes) in a few teleosts, the naming of these sequences appeared variable. The reasons could be (i) that the structure in this family is variable across teleosts, or (ii) unfortunate naming. Rather clear rules for the naming of genes in fish and mammals have been outlined by nomenclature committees, including the naming of orthologous and ohnologous genes. We therefore analyzed the connexin gene family in teleosts in more detail. We covered the range of divergence times in teleosts (eel, Atlantic herring, zebrafish, Atlantic cod, three-spined stickleback, Japanese pufferfish and spotted pufferfish; listed from early divergence to late divergence).
Results: The gene family pattern of connexin genes is similar across the analyzed teleosts. However, (i) several nomenclature systems are used, (ii) specific orthologous groups contain genes that are named differently in different species, (iii) several distinct genes have the same name in a species, and (iv) some genes have incorrect names. The latter includes a human connexin pseudogene, claimed as GJA4P, but which in reality is Cx39.2P (a delta subfamily gene often called GJD2like). We point out the ohnologous pairs of genes in teleosts, and we suggest a more consistent nomenclature following the outlined rules from the nomenclature committees. We further show that connexin sequences can indicate some errors in two high-quality chromosome assemblies that became available very recently.
Conclusions: Minimal consistency exists in the present practice of naming teleost connexin genes. A consistent and unified nomenclature would be an advantage for future automatic annotations and would make various types of subsequent genetic analyses easier. Additionally, roughly 5% of the connexin sequences point out misassemblies in the new high-quality chromosome assemblies from herring and cod.
Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis
Authors: Qu Nanfang , Qin Sanyu , Zhang Xuemei , Bo Xiaotong , Liu Zhengchun , Tan Chao , Wen Guiqiong , Jiang Haixing
Published: January 2020

Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.
Does the medical insurance system really achieved the effect of poverty alleviation for the middle-aged and elderly people in China?Characteristics of vulnerable groups and failure links.
Authors: Ma Meiyan , Li Ye , Wang Nianshi , Wu Qunhong , Shan Linghan , Jiao Mingli , Fu Xuelian , Li Heng , Sun Tao , Yi Bin , Tian Wanxin , Xia Qi , Shi Baoguo , Hao Yanhua , Yin Hui , Ning Ning , Gao Lijun , Liang Libo , Wang Jiahui
Published: January 2020

Objective ： We examined the physiological, household, and spatial agglomeration characteristics of the health poverty population in China. We identified weak links that affect the implementation of the medical insurance and further improve its effectiveness for health poverty alleviation. Methods: A national representative sample from the 2015 China Health and Pension Tracking Survey (CHARLS) was analyzed. The WHO recommended method was adopted to calculate catastrophic health expenditure (CHE) and impoverishment by medical expenses (IME). We created a binary indicator for IME as the outcome variable and applied the treatment-effect model to analyze the determinants of IME. Results ： The rate of IME was 7.2% of the overall population, compared to 20.3% of the sample households trapped in CHE. The rate of IME enrolled in insurance schemes was 7.4% higher than that of uninsured families (4.8%). Economic level, living area, family size, age of household head, having hospitalized members, and participating in insurance were statistically significant for the rate of IME. Conclusion ： The original poverty -promoting policies has not reached the maximum point of convergence with China’s current demand for health. The overlapped health vulnerabilities exacerbated the risk of poverty among the elderly and households with high health needs and utilization. In addition, the medical insurance schemes have proven to be insufficient for protection against economic burden of poor households. So, special health needs, age, and household capacity to pay should be comprehensively considered while strengthening the connection between the disease insurance scheme with supplementary insurance. Keywords: medical insurance, poverty alleviation, healthy poverty, catastrophic health expenditure, impoverishment by medical expenses.
C -reactive protein and albumin ratio for the diagnosis of complicated appendicitis in children
Authors: Feng Wei , Yang Qian-Yu , Zhao Xu-Feng , Li Miao-Miao , Cui Hua-Lei
Published: January 2020

Background: No reliably specific marker for complicated appendicitis has been identified. Serum C-reactive protein (CRP) and albumin (ALB) ratio (CRP/ALB ratio) has been a new inflammation-based prognostic score which is associated with the severity of inflammation. However, its value in the diagnosis of complicated appendicitis has not been studied. The aim of this study was to evaluate the predictive value of CRP/ALB ratio for complicated appendicitis in children. Methods: A retrospective study of 232 children with acute appendicitis was conducted with assessment of age, gender, symptom duration, albumin and blood routine indexes on admission. According to intraoperative findings and postoperative pathological results, patients were divided into the simple appendicitis group (127 cases) and complicated appendicitis group (105 cases). SPSS version 17 was used to analyse the data. Results: Of the 232 patients, 118 (50.9%) were male and 114 (49.1%) were female. The CRP/ALB ratio was higher in complicated appendicitis compared with simple appendicitis (p<0.05). Logistic regression analysis showed that the higher levels of mononuclear cell count (MC), CRP, procalcitonin (PCT) and CRP/ALB ratio were independent risk factors for complicated appendicitis in children. Receiver operating characteristic curve analysis showed that the area under the curve of CRP/ALB ratio (0.946) was was bigger than MC (0.619), CRP (0.906) and PCT (0.843). CRP/ALB ratio >1.43 was found to be a significant marker in predicting complicatedappendicitis with 91.4% sensitivity and 90.6% specificity. Compared with CRP/ALB ratio =<1.43, patients with CRP/ALB ratio >1.43 had a 102.22 times higher chance of complicated appendicitis (95% CI: 41.322 - 252.874). Conclusion: Admission CRP/ALB ratio was significantly higher in children with acute complicated appendicitis. It is a novel but promising hematological marker that aids the differentiation of acute complicated and simple appendicitis.
Production of an anti-angiogenic factor sFLT1 is suppressed via promoter hypermethylation of FLT1 gene in choriocarcinoma cells
Authors: Sasagawa Tadashi , Jinno-Oue Atsushi , Nagamatsu Takeshi , Morita Kazuki , Tsuruga Tetsushi , Mori-Uchino Mayuyo , Fujii Tomoyuki , Shibuya Masabumi
Published: January 2020

Background: Soluble Fms-like tyrosine kinase-1 (sFLT1) as an anti-angiogenic factor is abundantly expressed in placental trophoblasts. Choriocarcinoma, a malignant tumor derived from trophoblasts, is known to be highly angiogenic and metastatic. However, the molecular mechanism underlying angiogenesis in choriocarcinoma pathogenesis remains unclear. We aimed to investigate the mRNA expression and DNA methylation status of the FLT1 gene in human choriocarcinoma cells and trophoblast cells. Methods: qRT-PCR, Western blotting and ELISA were conducted to evaluate the mRNA and protein expression levels of sFLT1. 5-aza-2'-deoxycytidine (5azadC) treatment and bisulfite sequencing were used to study the FLT1 gene promoter methylation. The effect of sFLT1 on choriocarcinoma growth and angiogenesis was evaluated in a xenograft mouse model. Results: Expression of the FLT1 gene was strongly suppressed in choriocarcinoma cell lines compared with that in the primary trophoblasts. Treatment of choriocarcinoma cell lines with 5azadC, a DNA methyltransferase inhibitor, markedly increased in mRNA expression of three FLT1 splice variants and secretion of sFLT1 proteins. Bisulfite sequencing revealed that the CpG hypermethylation was observed at the FLT1 promoter region in choriocarcinoma cell lines and a human primary choriocarcinoma tissue but not in human trophoblast cells. Interestingly, in 5azadC-treated choriocarcinoma cell lines, sFLT1 mRNA expression and sFLT1 production were further elevated by hypoxic stimulation. Finally, as expected, sFLT1-expressing choriocarcinoma cells implanted into nude mice showed significantly slower tumor growth and reduced microvessel formation compared with GFP-expressing control choriocarcinoma cells. Conclusions: Inhibition of sFLT1 production by FLT1 silencing occurs via the hypermethylation of its promoter in choriocarcinoma cells. The stable expression of sFLT1 in choriocarcinoma cells resulted in the suppression of tumor growth and tumor vascularization in vivo . We suggest that the FLT1 gene may be a cell-type-specific tumor suppressor in choriocarcinoma cells.
Development of A Guideline for Reporting Mediation Analyses (AGReMA)
Authors: Cashin Aidan Gregory , McAuley James H , Lamb Sarah E , Hopewell Sally , Kamper Steven J , Williams Christopher M , Henschke Nicholas , Lee Hopin
Published: January 2020

Background There are a growing number of studies using mediation analysis to understand the mechanisms of health interventions and exposures. Recent work has shown that the reporting of these studies is heterogenous and incomplete. This problem stifles clinical application, reproducibility, and evidence synthesis. This paper describes the processes and methods that will be used to develop a guideline for reporting studies of mediation analyses (AGReMA). Methods/Design AGReMA will be developed over five overlapping stages. Stage one will comprise a systematic review to examine relevant evidence on the quality of reporting in published studies that use mediation analysis. In the second stage we will consult a group of methodologists and applied researchers by using a Delphi process to identify items that should be considered for inclusion in AGReMA. The third stage will involve a consensus meeting to consolidate and prioritise key items to be included in AGReMA. The fourth stage will involve production of AGReMA and an accompanying explanation and elaboration document. In the final stage we will disseminate the AGReMA statement via journals, conferences, and professional meetings across multiple disciplines. Discussion The development and implementation of AGReMA will improve the standardization, transparency, and completeness in the reporting of studies that use mediation analysis to understand the mechanisms of health interventions and exposures.
Leaving no one behind: lessons from implementation of policies for universal HIV treatment to universal health coverage
Authors: Assefa Yibeltal , Hill Peter S , Damme Wim Van , Dean Judith , Gilks Charles F
Published: January 2020

Background: The third Sustainable Development Goal (SDG-3) aims to ensure healthy lives and promote well-being for all at all ages. SDG-3 has a specific target on universal health coverage (UHC), which emphasizes the importance of all people and communities having access to quality health services without risking financial hardship. The objective of this study is to review progress towards UHC using antiretroviral treatment (ART) as a case study. Methods: We used a mixed-methods design including qualitative and quantitative approaches. We reviewed and synthesised the evidence on the evolution of the WHO HIV treatment guidelines between 2002 and 2019. We calculated ART coverage over time by gender, age group, and location. We also estimated ART coverage differences and ratios. Findings: ART guidelines have evolved from “treating the sickest” to “treating all”. ART coverage increased globally from under 7% in 2005 to 62% in 2018. There have been successes in increasing ART coverage in all populations and locations. However, progress varies by population and location in many regions. There is inequity in ART coverage: women (68%) versus men (55%), and adults (62%) versus children (54%). This inequity has widened over time, and with expanded ART eligibility criteria. On the other hand, data from at least one high-burden country (Ethiopia) shows that inequity among regions has narrowed over time due to the improvements in the primary health care systems and implementation of the public health approach in the country. Conclusion: ART coverage has increased at global, regional and national levels to all population groups. However, the gains have not been equitable among locations and populations. Policies towards universality may widen the inequity in resource-limited settings unless countries take precautions and “put the last first”. We argue that primary health care and public health approaches, with multi-sectoral actions and community engagement, are vital to minimize inequity, achieve UHC and leave no one behind.
Sputum and plasma adiponectin levels in clinically stable adult cystic fibrosis patients with CFTR I1234V mutation
Authors: AbdulWahab Atqah , Allangawi Mona , Thomas Merlin , Bettahi Ilham , Sivaraman Siveen K. , Jerobin Jayakumar , Chandra Prem , Abou-Samra Abdul-Badi , Ramanjaneya Manjunath
Published: January 2020

Background: Cystic fibrosis (CF) lung disease is associated with chronic inflammation leading to progress in lung function. Adiponectin is a predominantly anti-inflammatory adipokine that may have a role in CF lung. This study aims to determine total sputum and total plasma adiponectin levels in clinically stable adults CF patients with CFTR I1234V mutation, compared to plasma adiponectin levels in healthy controls and to investigate their correlations with body mass index (BMI) and spirometry in patients with CF. Methods: A cross-sectional study comprises 17 CF patients and 18 healthy controls. Adiponectin levels were measured by magnetic bead-based multiplex assay. Results: The mean age of adult CF patients was 22.9 years± 3.8 (18-30) and 76.5% CF patients had pancreatic sufficiency. The mean BMI in healthy controls was slightly higher than CF patients. The mean sputum adiponectin level was significantly lower than plasma adiponectin levels in CF patients and healthy controls (p<0.001), whereas no significant difference in plasma adiponectin levels between CF patients and healthy controls. The mean sputum adiponectin level was observed to be higher in CF patients with pancreatic insufficiency. Sputum adiponectin level was correlated positively with plasma adiponectin level in CF patients (r= 0.47, p=0.06). Sputum and plasma adiponectin levels in CF patients were correlated negatively with BMI and percentage predicted forced expiratory volume in 1 second (FEV1) and Forced vital capacity (FVC). Conclusions Sputum adiponectin may provide a minimally invasive tool in the assessment of an inflammatory status in CF patients. Further larger study to address any difference in sputum and plasma adiponectin levels among CF patients with pancreatic sufficiency versus pancreatic insufficiency.
Taxonomic and denitrifying bacteria communities associated with the interception of nitrate leaching by carbon amendment in the subsoil
Authors: Chen Chen , Han Hui , Meng Ya , Wu Hangyu , Jia Rui , Xu Ting , Ding guo-chun , Li Ji
Published: January 2020

The authors have withdrawn this preprint from Research Square
Prevalence and associated factors of erectile dysfunction among men DM patients in Gondar university hospital, Gondar Ethiopia
Authors: tesfaye tewodros , bayisa mulugeta , mesfin Nebiyu
Published: January 2020

Back ground- globally it is likely that 387 million people have DM and this number expected to increase to 592 million by the year 2035. WHO estimated the number of cases of diabetes in Ethiopia to be about 800thausadns in 2011 and expected that it would increase to about 1.8 million by the year 2030. Psychosomatic and sexual dysfunctions are one among different complication that DM patients come across during their disease course. Therefore this study aimed to estimate the prevalence and associated with erectile dysfunction among adult men DM patients in Ethiopia.Method-An institutional based cross-sectional study design was conducted among male DM patients at Gondar university referral hospital chronic illness clinic. Single population proportion sampling technique was used. 367 were selected proportionally using systematic random sampling technique. Face to face interview method was employed using a structured questionnaire for data collection. Data were analyzed descriptively and through bi-and multivariate logistic regression model.Result-The prevalence rate is 53.1%. The mean age of the respondents was 54.12(SD+16.5112) years age from 21-90 years. Majority of the respondents 158(43.1%) were Orthodox followers followed by Muslim, 113(30.8%), Protestant 55(15.0%) and Catholic 41(11.2%). the median monthly salary was 2000 Ethiopian Birr. BMI of most respondents was within the range of 18.5-24.9. ED was significantly associated with Age, Duration of DM and Alcohol.Conclusion- Finding of this study indicated that ED is a major public and self issue with its multi-factorial among male DM. The evidence from this study found that being aged, alcoholic and longer duration of DM was significantly associated with ED.Key words- Erectile dysfunction, prevalence, male DM patients, Gondar University Referral Hospital.
Magnitude of screening for gestational diabetes mellitus in an urban setting in Tanzania; a cross-sectional analytic study
Authors: Mukuve Akampa Mbaaga , Mgonja Miriam Lucy , Sendagire Ibrahim , Noorani Mariam
Published: January 2020

Background: Medical screening detects risk factors for disease or presence of disease in otherwise well persons in order to intervene early and reduce morbidity and mortality. During antenatal care (ANC) it is important to detect conditions that complicate pregnancy, like gestational diabetes mellitus (GDM). Despite international and local guidelines recommending screening for GDM during ANC, there is evidence to suggest that the practice was not being carried out adequately. A major challenge may be lack of consensus on uniform GDM screening and diagnostic guidelines internationally and locally. The primary objective was to determine the magnitude of screening for GDM among women receiving ANC at the Aga Khan Hospital, Dar es Salaam and Muhimbili National Hospital, Dar es Salaam. Secondary objectives were: to determine the methods used by health practitioners to screen for GDM, to determine the magnitude of undiagnosed gestational diabetes mellitus among women attending ANC and factors associated with screening for GDM among these women. Methods: A cross-sectional analytical study was done. Data collection was done using pre-tested questionnaires and reviewing antenatal care records. The proportion of women attending ANC who were screened for GDM was determined. The 75g Oral Glucose Tolerance Test (OGTT) was offered to women who had not been screened after education and consent. Results: Only 107 out of 358 (29.9%) had been offered some form of GDM screening. Tests used for GDM screening were random blood sugar (56.8%), fasting blood sugar (32.8%), HbA1C (6%) and 75g OGTT (3.4%). The uptake of the OGTT was 27%. Of these women the prevalence of GDM was 27.4%. Factors associated with screening for GDM were history of big baby, history of pregnancy induced hypertension and participant awareness of GDM (all p : <0.05). Conclusions: Screening for GDM among women attending ANC was lower than the World Health Organization target. Efforts should be directed towards promoting GDM screening, increasing awareness about GDM and developing more effective screening methods.
MtOrt: An empirical mitochondrial amino acid substitution model for evolutionary studies of Orthoptera insects
Authors: Chang Huihui , Nie Yimeng , Zhang Nan , Zhang Xue , Sun Huimin , Mao Ying , Qiu Zhongying , Huang Yuan
Published: January 2020

Background Amino acid substitution models play an important role in inferring phylogenies from mitochondrial proteins. Although different amino acid substitution models have been proposed, only a few were estimated from mitochondrial protein sequences for specific taxa such as the mtArt model for Arthropoda. The increasing of mitochondrial genome data from broad Orthoptera taxa provides an opportunity to estimate the Orthoptera-specific mitochondrial amino acid empirical model. Results We sequenced complete mitochondrial genomes of 54 Orthoptera species, and then estimated an amino acid substitution model (named mtOrt) by maximum likelihood method based on the 283 complete mitochondrial genomes available currently. The results indicated that there are obvious differences between mtOrt and the existing model, and the new model can better fit the Orthoptera mitochondrial protein datasets. Moreover, topologies of trees constructed using mtOrt and existing models are frequently different. MtOrt does indeed have an impact on likelihood improvement as well as tree topologies. The comparisons between the topologies of trees constructed using mtOrt and existing models show that the new model outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein data. Conclusions The new mitochondrial amino acid substitution model of Orthoptera shows obvious differences from the existing models, and outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein sequences.
Comparing Intervention Strategies for Reducing Clostridioides difficile Transmission in Acute Healthcare Settings: An Agent-Based Modeling Study
Authors: Stephenson Brittany , Lanzas Cristina , Lenhart Suzanne , Ponce Eduardo , Bintz Jason , Dubberke Erik R. , Day Judy
Published: January 2020

Background Clostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting. Methods We developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI susceptibility, and tracks contamination levels of ward rooms by C. difficile. Interventions include two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination. Results Increased HCW contact precaution compliance with CDI patients was ranked as the most effective intervention in decreasing colonizations, with reductions up to 56%. Antibiotic stewardship practices were highly ranked after contact precaution compliance. Vaccination and reduction of high-risk antibiotics were the most effective intervention in decreasing CDI. Vaccination reduced CDI cases to up to 90%, and the reduction of high-risk antibiotics decreased CDI cases up to 23%. Conclusions Overall, interventions that decrease patient susceptibility were the most effective interventions in reducing both colonizations and CDI cases.
Large-scale movements and site fidelity of bull sharks (Carcharhinus leucas) at Reunion Island (Indian ocean)
Authors: Soria Marc , Tremblay Yann , Blaison Antonin , Forget Fabien , Crochelet Estelle , Dagorn Laurent
Published: January 2020

Two bull sharks ( Carcharhinus leucas ) were tagged in coastal waters off Reunion Island in the tropical Indian Ocean and where tracked for 174 and 139 days using both popup satellite archival tags (pSAT) and acoustic tags. Both sharks spent a majority of their time inshore (58.1% and 89.9% in the male and the female respectively). The female performed short excursions. The male alternated residence time along the coast with wide ranging movements and performed one extensive open-ocean excursion near a seamount situated at more than 200 km from the island. The differences in the residency and home range of both sharks probably reflect different patterns of foraging and mating behaviors in the male and the female. These results underline the importance of developing risk-mitigation management taking into account the movements of sharks, and of double tagging in telemetry studies that attempt to measure the degree of fidelity of a species.
Association of Lean Body Mass to Menopausal Symptoms: The Study of Women’s Health Across the Nation
Authors: Woods Rosanne , Hess Rebecca , Biddington Carol , Federico Marc
Published: January 2020

Background The purpose of this study was to examine the association of lean body mass (LBM) to the development of vasomotor symptoms (VMS) as women transition through menopause. Methods This study is a secondary use of data available for public use from follow up visits six through 10 for participants in the Study of Women’s Health Across the Nation. The study examined 2,533 women, between the ages 42 – 52 years, each year over a10-year period. Data was modeled for associations of lean body mass and VMS. Changes in LBM since prior visit and since baseline were also modeled along with differences in means using binary logistic regression, adjusting for covariates. Results LBM was significantly associated to concurrent VMS ( p = .036), percent change in LBM since prior visit ( p = .003), percent change since baseline ( p <.001), and overall means associations ( p = .023). LBM was not significant for VMS at individual visit measures. In mixed regression modeling, time was significant ( p <.0001) at all visits. The estimated probability of developing VMS decreases significantly as LBM increases. Conclusions Lean body mass is negatively associated with incident VMS. Our data suggests that maintaining higher levels of LBM during the menopausal transition may be protective against the development of VMS. Every woman will experience menopause in her life and the ability to potentially prevent the onset of specific symptoms through basic interventions, such as resistance training to increase lean body mass, may positively impact this large population.
Genetic characteristics and diversity of Korean Jeju Black cattle by whole genome SNP markers
Authors: Alam Mohammad Zahangir , Son Hyo Jung , Lee Yun Mi , Hanna Lauren Hulsman , Riley David , Mannen Hideyuki , Sasazaki Shinji , Park Se Pill , Kim Jong Joo
Published: January 2020

Background Conservation and genetic improvement of cattle breeds requires to know the information about genetic diversity and population structure of animals. This study investigated the genetic diversity and population structure among the three breeds raised in Korean peninsula. Three popular breed found in Korea , i.e. Jeju Black, Hanwoo, Holstein with other six breeds such as Angus, Hereford, Brown Wagyu, Black Wagyu, Brahman and Nellore was examined in this study. Genetic diversity within the cattle breeds was analyzed using the popular measures of genetic diversity namely minor allele frequency (MAF), observed and expected heterozygosity (H O and H E ), inbreeding coefficient (F IS ) and past effective population size (N E ). Molecular variance and population structure were performed among the nine cattle breeds using model-based clustering (ADMIXTURE) analysis. Genetic distances between breed pairs were evaluated using Nei’s genetic distance (D A ) and with Weir and Cockerham’s F ST . Results This study revealed that Jeju Black cattle had lowest level of heterozygocity (HE = 0.21) among the studied taurine cattle breeds ranging from 0.25 to 0.30, and low MAF of 0.16, while other breeds have MAF ranging 0.11~0.21. The level of inbreeding was -0.076 in case of Jeju Black as compared to other breed (-0.018 ~ -0.118). PCA analysis and neighbor-joining (NJ) tree showed a clear separation of Jeju Black cattle from other local and exotic cattle breeds. Model-based clustering also revealed a distinct pattern of admixture of Jeju Black cattle having no clustering with other studied populations. The F ST value between Jeju Black cattle and Hanwoo was 0.106, which was lowest across the breeds ranging from 0.161 to 0.274, indicating some degree of genetic closeness of Jeju Black cattle with Hanwoo. The N E of Jeju Black cattle was 38, whereas Hanwoo was 209 in the most recent 13 generation ago. Conclusion This study indicates an alarming trend of reducing effective population size in Jeju Black cattle. Thus, a sustainable breeding policy should be implemented to increase the population of Jeju Black cattle for the genetic improvement and future conservation.