bluuebunny/crossref_metadata_2025 huggingface dataset:
In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City
Authors: Ashrap Pahriya , Meeker John D. , Sánchez Brisa N. , Basu Niladri , Tamayo-Ortiz Marcela , Solano-González Maritsa ,   Adriana Mercado-García4, Téllez-Rojo Martha M. , Peterson Karen E. , Watkins Deborah
Published: October 2020

Background: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.Methods: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone levels [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10-18 years). We used linear regression to independently examine urinary metal levels in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.Results: In utero and prepubertal concentrations of some urinary metals were associated with increased levels of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.Conclusion: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep
Authors: Dong Kunzhe , Yang Min , Han Jiangang , Ma Qing , Han Jilong , Song Ziyi , Luosang Cuicheng , Gorkhali Neena Amatya , Yang Bohui , He Xiaohong , Ma Yuehui , Jiang Lin
Published: October 2020

Background: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures.Results: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. Conclusions: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.
Praziquantel treatment coverage among school age children against  Schistosomiasis and associated factors in Ethiopia: a cross-sectional survey, 2019
Authors: Dea Yilma Chisha , Zerdo Zerihun , Asnakew Mekuria , Churko Chuchu , Yihune Manaye , Teshome Abinet , Nigussu Nebiyu , Seife Fikire , Getachew Birhanu , Sileshi Markos
Published: October 2020

Background: World Health Organization estimated that 779 million people are at risk of getting schistosomiasis (SCH) and 240 million people were infected worldwide. SCH due to schistosoma mansoni (S. mansoni) is a wide public health problem in Ethiopia. The aim of the survey was to quantify national and district disaggregated treatment coverage status for SCH and compare validated coverage with the one reported. Methods: Community based cross-sectional survey was conducted in April 2019 among households with school age children (SAC) 5-14 years in seven purposively selected districts of the country. Segments to be surveyed were randomly selected and households to be interviewed from each segment were determined using systematic sampling technique. A total of 3,378 households visited and 5,679 SAC (5-14 years) were interviewed.Results: Overall reported treatment coverage of Praziquantel (PZQ) against SCH was 4286 (75.5%). Males were 27% more likely to swallow the drug (AOR= 1.27; 95% CI: 1.09, 1.47) than females. SAC with age 10-14 years were 45% more likely to swallow the drug compared with their counter parts (5-9 years), (AOR =1.45; 95% CI: 1.25, 1.69). There is statistically significant association between PZQ swallowing status with school enrollment. (AOR= 20.90, 95% CI: 17.41, 25.08). Swallowing status of PZQ against SCH significantly higher for SAC treated in districts applied integrated treatment approach (87.5%) compared with SAC treated in vertical treatment approach (72.5%); P-value <0.001. SACs were asked for reasons for not taking the drug and the main reported reason for not swallowing PZQ in the present study was none attending of the school.Conclusions Over all treatment coverage of PZQ against SCH in the present study was 75.5%. Although it is in accordance with WHO recommendation for Ethiopia, national programmatic improvements are necessary to achieve higher coverage in the future. To increase treatment coverage for PZQ against SCH in Ethiopia, school based training should target all schools. Moreover, mobilization, sensitization and implementation of the community wide treatment need to be improved.
Socio-demographic associations of HIV among women attending antenatal care in selected rural primary care facilities in South Africa's Eastern Cape province.
Authors: Mabunda Sikhumbuzo A , Sigovana Khuthala , Chitha Wezile , Apalata Teke , Nomatshila Sibusiso
Published: October 2020

Background: To effectively reduce vertical HIV transmission requires a reduction of HIV prevalence and incidence among pregnant women and a full understanding of its epidemiology. The study aimed to determine the prevalence of HIV among women attending antenatal care and further determine spousal support during antenatal care attendance in rural areas in Eastern Cape province, South Africa. Methods: A Cross-sectional study of women attending antenatal care in four Primary Care facilities was conducted using an interviewer-administered questionnaire which collected information on socio-demographic characteristics and medical history. Binomial logistic regression analyses were used to determine factors associated with HIV and to estimate the prevalence ratio (PR). The 95% confidence interval (95%CI) is used for precision of estimates; p≤0.05 for statistical significance. Results: A total of 343 participants were included in the final analysis. The antenatal HIV prevalence was 38.2% (95%CI: 33.2 – 43.9). For 75% of the women, the HIV diagnosis was made 141 days before the date of the interview (median=77 days, interquartile range=42-141 days). Participants between the age of 30 to 39 years were 50% more likely to be HIV positive compared to those who were between the age of 20 to 29 years, these differences were statistically significant (PR=1.5; p-value=0.001). Furthermore, self-employed women were 30% less likely to be HIV positive when compared to unemployed participants, this was also statistically significant (PR=0.7; p-value<0.0001). Conclusion: Despite a 100% antenatal HIV testing rate, the antenatal HIV prevalence remains high in this population, coupled with no spousal attendance in antenatal care. It is important to move beyond awareness about the HIV status to actionable strategies of reducing the HIV incident cases. It is therefore important to remain vigilant and monitor mother-to-child transmission that could be associated with this increased prevalence.
Breeding farm, level of feeding and presence of antibiotics in the feed influence rabbit cecal microbiota
Authors: Velasco-Galilea María , Guivernau Miriam , Piles Miriam , Viñas Marc , Rafel Oriol , Sánchez Armand , Ramayo-Caldas Yuliaxis , González-Rodríguez Olga , Sánchez Juan P.
Published: October 2020

Background: the effect of the production environment and different management practices in rabbit cecal microbiota remains poorly understood. While previous studies have proved the impact of the age or the feed composition, research in the breeding farm and other animal management aspects, such as the presence of antibiotics in the feed or the level of feeding, is still needed. Characterization of microbial diversity and composition of growing rabbits raised under different conditions could help better understand the role these practices play in cecal microbial communities and how it may result in different animal performance.Results: four hundred twenty-five meat rabbits raised in two different facilities, fed under two feeding regimes (ad libitum or restricted) with feed supplemented or free of antibiotics, were selected for this study. A 16S rRNA gene-based assessment through the MiSeq Illumina sequencing platform was performed on cecal samples collected from these individuals at slaughter. Different univariate and multivariate approaches were conducted to unravel the influence of the different factors on microbial alpha diversity and composition at phylum, genus and OTU taxonomic levels. The animals raised in the facility harboring the most stable environmental conditions had greater, and less variable, microbial richness and diversity. Bootstrap univariate analyses of variance and sparse partial least squares-discriminant analyses endorsed that farm conditions exerted an important influence on rabbit microbiota since the relative abundances of many taxa were found differentially represented between both facilities at all taxonomic levels characterized. Furthermore, only five OTUs were needed to achieve a perfect classification of samples according to the facility where animals were raised. The level of feeding and the presence of antibiotics did not modify the global alpha diversity but had an impact on some bacteria relative abundances, albeit in a small number of taxa compared with farm, which is consistent with the lower sample classification power according to these factors achieved using microbial information.Conclusions: this study reveals that factors associated with the farm effect and other management factors, such as the presence of antibiotics in the diet or the feeding level, modify cecal microbial communities. It highlights the importance of offering a controlled breeding environment that reduces differences in microbial cecal composition that could be responsible for different animal performance.
Adherence predictor variables in AIDS patients: An empirical study using the data mining-based RFM model
Authors: Li Min , Wang Qunwei , Shen Yinzhong
Published: October 2020

Background: Highly active antiretroviral therapy (ART) is still the only effective method to stop the disease progression in acquired immunodeficiency syndrome (AIDS) patients. However, poor adherence to the therapy makes it ineffective. In this work, we construct an adherence prediction model of AIDS patients using the classical recency, frequency and monetary value (RFM) model in the data mining-based customer relationship management model to obtain adherence predictor variables.Methods: We cleaned 257305 diagnostic data elements of AIDS outpatients in Shanghai from August 2009 to December 2019 to obtain 16440 elements. We tested the RFM and RFm (R: recent consultation month, F: consultation frequency, M/m: total/average medical costs per visit) models, three clustering methods (K-means, Kohonen and two-step clustering) and four decision algorithms (C5.0, the classification and regression tree, Chi-square Automatic Interaction Detector and Quick, Unbiased, Efficient, Statistical Tree) to select the optimal combination. The optimal model and clustering analysis were used to divide the patients into two groups (good and poor adherence), then the optimal decision algorithm was used to construct the prediction model of adherence and obtain its predictor variables.Results: The results revealed that the RFm model, K-means clustering analysis and C5.0 algorithm were optimal. After three rounds of k-means clustering analysis, the optimal RFm clustering model quality was 0.8, 10614 elements were obtained, including 9803 and 811 from patients with good or poor adherence, respectively, and five types of patients were identified. The prediction model had an accuracy of 100% with the recent consultation month as an important adherence predictor variable.Conclusions: This work presented a prediction model for medication adherence in AIDS patients at the designated AIDS center in Shanghai, using the RFm model and the k-means and C5.0 algorithms.
Sequential bilateral Behçet’s neuroretinitis associated with prepapillary vitreous exudate: case report
Authors: Ksiaa Imen , Aoun Safa Ben , Zina Sourour , Nefzi Dhouha , Khochtali Sana , Khairallah Moncef
Published: October 2020

Objective: To describe a case of Behçet disease (BD) uveitis manifesting with sequential bilateral prepapillary inflammatory vitreous exudate (PIVE) documented with multimodal imaging, including swept source optical coherence tomography (SS OCT) and OCT angiography. Material and Methods: A single case report.Results: A 37-year-old man developed sequential bilateral PIVE, initially misdiagnosed as toxoplasmic neuroretinitis, before extraocular features of BD became evident and the patient treated accordingly. SS OCT showed at the acute phase in both eyes a typical “mushroom-shaped” prepapillary hyperreflectivity of the PIVE. SS OCTA demonstrated a corresponding prepapillary hypointense area due to shadowing effect, decreasing in size while scanning deeper layers. It also detected peripapillary retinal hypervascularity in both eyes and a sectoral area of flow signal loss in the first involved left eye. Visual acuity improved following the resolution of the PIVE and associated acute inflammatory changes in both eyes. The left eye showed residual optic disc pallor and retinal nerve fiber layer defects.Conclusion: Sequential bilateral PIVE may occur in the absence of other clinical features of BD. SS OCT and OCTA can provide useful information for the diagnosis and management of PIVE and underlying optic nerve inflammation.
The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors
Authors: Karimian Zahra , Mavoungou Sandra , Salem Joe-Elie , Tubach Florence , Dechartres Agnes
Published: October 2020

Background – While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs.
Methods – PubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources.
Results – Of 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8% and 8.8% of publications respectively, compared to 11.8% and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources.
Conclusions – The reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.
Stakeholders’ perspectives of comprehensive sexuality education in Iranian male adolescents
Authors: gelehkolaee keshvar samadaee , Maasoumi Raziyeh , Azin Seyed Ali , Nedjat Saharnaz , Parto Moslem , Hajiabadi Ilia Zamani
Published: October 2020

Background: A coherent sexuality education program for adolescents is part of their sexual and reproductive rights and can help them have a healthier future. Therefore, the aim of this study was to explore the perspectives and intervention preferences of Iranian stakeholders regarding comprehensive sexuality education (CSE) in male adolescents based on the IMB model (Information, Motivation, Behavioral skills). Methods: This study was a qualitative study that was analyzed through a directed content analysis approach. Individual interviews and focused group discussions (FGDs) were used for data collection. The data were collected through in-depth semi-structured interviews with stakeholders in two schools and the Education Department in Sari and the Ministry of Health and Ministry of Education in Tehran from March 2019 to August 2019. Data saturation was achieved after 28 interviews and 1 FGDs with 9 participants. Finally, two sets of data were coded and analyzed using directed content analysis. Results: In this study, five themes emerged as (1) role of institutions; (2) role of organizations; (3) need for stakeholder’s partnership; (4) need for adolescent sexuality socialization management; and (5) need for enhancing the teachers’ professional competence, which seemed to influence the implementation of CSE in male adolescents. Participants also expressed a number of intervention preferences for CSE. The most important of these was the change in macro policies, helping to create a culture against all forms of violence and breaking the taboo of sexuality education for children and adolescents.Conclusions: The results of this study revealed the need for a CSE program for adolescents' sexuality socialization. The finding showed that teachers required training to enhance their professional competence about sexuality issues. Therefore, it is necessary to design and implement culture-appropriate skill based programs to enhance the teachers’ professional competence regarding the adolescents’ sexual health.
Assessment of Intracellular Calcium and Plasmalemmal Membrane Potential in Cryopreserved Metaphase II Mouse Oocytes
Authors: Ammar Omar Farhan , Moodley Therishnee
Published: October 2020

Objectives: Ca2+ is critical for normal oocyte activation and fertilization, and any alteration to the Ca2+ homeostasis may lead to failed fertilization or even cell death. It has been shown that intracellular Ca2+ is increased in bovine and human oocytes when cultured in vitro. Additionally, ATP sensitive potassium channels have been characterised recently in human and Xenopus oocytes. Glibenclamide a KATP channel blocker was shown to protect human oocytes from Ca+2 overloading via inhibition of plasmalemmal KATP channels. This research note aims to demonstrate the effects of oxidative stress and in vitro ageing on the intracellular Ca+2 and plasmalemmal membrane potential dynamics in cryopreserved metaphase II (MII) mouse oocytes. Also, this study aims to show if glibenclamide (a KATP channel blocker ) has a role in regulating intracellular Ca+2 and plasmalemmal membrane potential through KATP channels in cryopreserved metaphase II mouse oocytes.Results: our data did not show an increase in intracellular Ca2+ in untreated cryopreserved mouse oocytes loaded with Fluo-3 AM dye. However, an increase in the plasmalemmal membrane potential was noticed (hyperpolarization). Glibenclamide has shown no significant effect on Ca2+ and plasmalemmal membrane potential.
An efficient computational Method for Predicting Drug-Target Interactions using Weighted Extreme Learning Machine and Speed Up Robot Features
Authors: Yong An Ji , Fan-Rong Meng , Zi-Ji Yan
Published: October 2020

Background: Prediction of novel Drug–Target interactions (DTIs) plays an important role in discovering new drug candidates and finding new proteins to target. In consideration of the time-consuming and expensive of experimental methods. Therefore, it is a challenging task that how to develop efficient computational approaches for the accurate predicting potential associations between drug and target. Results: In the paper, we proposed a novel computational method called WELM-SURF based on drug fingerprints and protein evolutionary information for identifying DTIs. More specifically, for exploiting protein sequence feature, Position Specific Scoring Matrix (PSSM) is applied to capturing protein evolutionary information and Speed up robot features (SURF) is employed to extract sequence key feature from PSSM. For drug fingerprints, the chemical structure of molecular substructure fingerprints was used to represent drug as feature vector. Take account of the advantage that the Weighted Extreme Learning Machine (WELM) has short training time, good generalization ability, and most importantly ability to efficiently execute classification by optimizing the loss function of weight matrix. Therefore, the WELM classifier is used to carry out classification based on extracted features for predicting DTIs. The performance of the WELM-SURF model was evaluated by experimental validations on enzyme, ion channel, GPCRs and nuclear receptor datasets by using fivefold cross-validation test. The WELM-SURF obtained average accuracies of 93.54%, 90.58%, 85.43% and 77.45% on enzyme, ion channels, GPCRs and nuclear receptor dataset respectively. We also compared our performance with the Extreme Learning Machine (ELM), the state-of-the-art Support Vector Machine (SVM) on enzyme and ion channels dataset and other exiting methods on four datasets. By comparing with experimental results, the performance of WELM-SURF is significantly better than that of ELM, SVM and other previous methods in the domain.Conclusion: The results demonstrated that the proposed WELM-SURF model is competent for predicting DTIs with high accuracy and robustness. It is anticipated that the WELM-SURF method is a useful computational tool to facilitate widely bioinformatics studies related to DTIs prediction.
The preoperative and the postoperative neutrophil-to-lymphocyte ratio both predict prognosis in gastric cancer patients
Authors: Kim Eun Young , Song Kyo Young
Published: October 2020

Background: Both the preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR) have been proposed to predict the long-term prognosis in some cancers, including gastric cancer. The present study investigated the prognostic impact of postoperative NLR, and its preoperative to postoperative changes, in patients with gastric cancer. Methods: From 2009 to 2012, 1,227 consecutive patients who underwent curative surgery for gastric cancer were enrolled in this study. The optimal cut-off value for the postoperative 6-month NLR was 1.7, as determined by receiver operating characteristic curve analysis. Patients were categorized into low- and high-NLR groups based on their postoperative NLR. Four additional groups (low to low, low to high, high to low, and high to high groups) were defined based on the preoperative to postoperative change in the NLR. Results: The 5-year overall survival (OS) rates of the low- and high-NLR group were 90.7% and 83.0%, respectively (P < 0.001). The differences in OS were significant in stage I and stage III gastric cancer patients. (P = 0.000 and 0.012, respectively). Postoperative NLR was an independent prognostic factor for OS (hazard ratio [HR] = 1.556; P = 0.010). The high to high NLR change was a significant predictor of OS (HR = 1.817; P = 0.003). Conclusions: High preoperative and postoperative NLRs, and especially the persistent elevation of preoperative to postoperative NLR, were significant poor prognostic factors for OS in patients with gastric cancer.
Pancreatic Lineage Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells on Acellular Pancreatic Bioscaffold
Authors: Li Zhao , Du Yue , Wang Xin
Published: October 2020

Background:We evaluated(1) the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) into pancreatic lineage cells on rat acellular pancreatic bioscaffold (APB) and (2) the effect of differentiated BMSCs on chronic pancreatitis in vivo.Methods:After BMSCs were isolated and characterized, they were dynamically cultured on APB and statically cultured in tissue culture flasks (TCFs), with or without growth factor(GF) in both culture systems. We assessed cytological behavior, such as the proliferation and differentiation of BMSCs, by morphological observation, flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative real-time/reverse transcriptase polymerase chain reaction, and Western blot analysis. For the in vivo study, we evaluated the pancreatic fibrosis and pathological scores.We detected the expression of α-SMA,collagen types I and III,and IL-10 in pancreatic tissue by ELISA.Results:The most appropriate flow rate for the dynamic culture of BMSCs was 4mL/min. The proliferation rates of BMSCs in the APB groups were significantly higher than in the TCF groups.During the pancreatic lineage cell differentiation process, APB induced BMSCs to express mRNA markers such as PDX-1 and PTF-1 at higher levels. In contrast, the marker Oct4 was expressed at a lower level in the APB group. All tested pancreatic cytokeratins, including α-Amy, CK7, Flk-1, and C-peptide, were expressed at higher levels in the APB group. The secretion of metabolic enzymes, such as Amy and insulin, was higher in the APB system. By scanning electron microscopy and transmission electron microscopy, the ultrastructure of BMSCs in the APB group further revealed the morphological characteristics of pancreatic-like cells. In the in vivo study, the expression of α-SMA and collagen types I and III in tissues was significantly lower in differentiated BMSCs group, whereas the levels of IL-10 in pancreatic tissue were higher in differentiated BMSCs with significant difference. In addition, in both the in vitro and the in vivo study, GF significantly improved proliferation, differentiation, and pancreatic cell therapy.Conclusion: Our data showed (1) the capacity of APB, a three-dimensional pancreatic biomatrix, to promote BMSC differentiation toward pancreatic lineage and pancreatic-like phenotypes, and (2) the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.
Follistatin-like 1 (FSTL1) is a prognostic biomarker and correlated with immune cell infiltration in gastric cancer
Authors: Li Li , Huang Shanshan , Yao Yangyang , Chen Jun , Li Junhe , Xiang Xiaojun , Deng Jun , Xiong Jianping
Published: October 2020

Background: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated. Methods: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real‐time quantitative PCR (RT-qPCR) was using to analyzed protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates was analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA) and LinkedOmics database. Results: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and Immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC. Conclusions: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.
Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection
Authors: Hu Zhi-Qiang , Zhou Zheng-Jun , Luo Chu-Bin , Xin Hao-Yang , Li Jia , Yu Song-Yang , Zhou Shao-Lai
Published: October 2020

Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.
Atrial Matrix Remodeling in Atrial Fibrillation Patients with Aortic Stenosis
Authors: Fragão-Marques Mariana , Miranda I , Martins D , Barroso Isaac , Mendes C , Pereira-Neves A , Falcão-Pires I , Leite-Moreira A
Published: October 2020

Background: This study aimed to evaluate atrium extracellular matrix remodeling in Atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. Methods: A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to Aortic valve replacement (AVR) surgery in a tertiary hospital were selected. Results: Fibrosis was significantly increased in the AF group when compared to Sinus Rhythm (SR) patients (p=0.024). Moreover, cardiomyocyte area was significantly higher in AF patients vs SR patients (p=0.008). Conversely, collagen III gene expression was increased in AF patients (p=0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p=0.006). TIMP1 (p=0.004) and TIMP2 (p=0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p=0.0159) and mean (p=0.031) gradients demonstrated a negative association with serum TIMP1. Conclusion: Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.
Epidemiology of Sheep Lice and Efficacy Evaluation of 60% Diazinon and 1% Ivermectin against Bovicola ovis in Sayint District, South Wollo, Ethiopia
Authors: Legesse Simegn , Hailemelekot Mussie , Tamrat Habtamu , Ferede Yeshwas
Published: October 2020

Background

Sheep lice, caused by Bovicola ovis are very common in Ethiopia. It can result decreased production and reproduction, downgrading and rejection of skins in tannery industries. A cross-sectional and experimental study were conducted in Sayint District, South Wollo, Ethiopia which aims to determine the prevalence of sheep lice with the associated risk factors, identify the major sheep lice species and evaluate the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis. Study kebeles and animals were selected using purposive and multistage sampling techniques. Accordingly, a total of 232 sheep were sampled to estimate the prevalence of sheep lice. Fifteen sheep for in-vivo and 80 Bovicola ovis lice for in-vitro test were used for drug efficacy trial, by using completely randomized design.
Results

The overall prevalence of sheep lice in this study was 48%. Hair length (OR = 2, P = 0.00), body condition (OR = 1.9, P = 0.02), agro ecology (OR = 1.19, P = 0.00) and season (OR = 2, P = 0.01) were significantly (P < 0.05) associated with sheep lice infestation. The dominant sheep lice species in the study area were Bovicola ovis with prevalence of 83% and mixed infestation of 17% Bovicola ovis with Linognatus ovillus. In this study, the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis were 97% and 81%, respectively.
Conclusion

The overall prevalence of sheep lice infestation in the present study area was higher, in which Bovicola ovis was predominant and resistant against 1% Ivermectin. Therefore, tailor made intervention is required with a view to reducing the prevalence of sheep lice infestation and addressing drug resistance in the study area.
Structure and assembly of the S-layer determine virulence in C. difficile
Authors: Banerji Oishik , Lanzoni-Mangutchi Paola , Vaz Filipa , Barwinska-Sendra Anna , Wilson Jason , Kirk Joseph , O'Beirne Shauna , Basle Arnaud , Omari Kamel El , Wagner Armin , Fairweather Neil , Douce Gillian , Bullough Per , Fagan Robert P , Salgado Paula
Published: October 2020

Many bacteria and archaea possess a cell surface layer – S-layer – made of a 2D protein array that covers the entire cell. As the outermost component of the cell envelope, S-layers play crucial roles in many aspects of cell physiology. Importantly, many clinically relevant bacterial pathogens possess a distinct S-layer that forms an initial interface with the host, making it a potential target for development of species-specific antimicrobials. Targeted therapeutics are particularly important for antibiotic resistant pathogens such as Clostridioides difficile, the most frequent cause of hospital acquired diarrhea, which relies on disruption of normal microbiota through antibiotic usage.
Despite the ubiquity of S-layers, only partial structural information from a very limited number of species is available and their function and organization remains poorly understood.
Here we report the first complete atomic level structure and in situ assembly model of an S-layer from a bacterial pathogen and reveal its role in disease severity. SlpA, the main C. difficile S-layer protein, assembles through tiling of triangular prisms abutting the cell wall, interlocked by distinct ridges facing the environment. This forms a tightly packed array, unlike the more porous S-layer models previously described. We report that removing one of the SlpA ridge features dramatically reduces disease severity, despite being dispensable for overall SlpA structure and S-layer assembly. Remarkably, the effect on disease severity is independent of toxin production and bacterial colonization within the mouse model of disease.
Our work combines X-ray and electron crystallography to reveal a novel S-layer organization in atomic detail, highlighting the need for multiple technical approaches to obtain structural information on these paracrystalline arrays. These data also establish a direct link between specific structural elements of S-layer and virulence for the first time, in a crucial paradigm shift in our understanding of C. difficile disease, currently largely attributed to the action of potent toxins.
This work highlights the crucial role of S-layers in pathogenicity and the importance of detailed structural information for providing new therapeutic avenues, targeting the S-layer. Understanding the interplay between S-layer and other virulence factors will further enhance our ability to tackle pathogens carrying an S-layer. We anticipate that this work provides a solid basis for development of new, C. difficile-specific therapeutics, targeting SlpA structure and S-layer assembly to reduce the healthcare burden of these infections.
Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis
Authors: Cecere Germano , Singh Meetali , Cornes Eric , Li Blaise , Quarato Piergiuseppe , Bourdon Loan , Dingli Florent , Loew Damarys , Procaccia Simone
Published: October 2020

In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with ribosome translation in the cytoplasm, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.
How to build a water-splitting machine: structural insights into photosystem II assembly
Authors: Zabret Jure , Bohn Stefan , Schuller Sandra , Arnolds Oliver , Möller Madeline , Meier-Credo Jakob , Liauw Pasqual , Chan Aaron , Tajkhorshid Emad , Langer Julian , Stoll Raphael , Krieger-Liszkay Anja , Engel Benjamin , Rudack Till , Schuller Jan , Nowaczyk Marc
Published: October 2020

Biogenesis of photosystem II (PSII), nature’s water splitting catalyst, is assisted by auxiliary proteins that form transient complexes with PSII components to facilitate stepwise assembly events. Using cryo-electron microscopy, we solved the structure of such a PSII assembly intermediate with 2.94 Å resolution. It contains three assembly factors (Psb27, Psb28, Psb34) and provides detailed insights into their molecular function. Binding of Psb28 induces large conformational changes at the PSII acceptor side, which distort the binding pocket of the mobile quinone (QB) and replace bicarbonate with glutamate as a ligand of the non-heme iron, a structural motif found in reaction centers of non-oxygenic photosynthetic bacteria. These results reveal novel mechanisms that protect PSII from damage during biogenesis until water splitting is activated. Our structure further demonstrates how the PSII active site is prepared for the incorporation of the Mn4CaO5 cluster, which performs the unique water splitting reaction.
Supply chain diversity buffers cities against food shocks
Authors: Mejia Alfonso , Gomez Michael , Ruddell Ben , Rushforth Richard
Published: October 2020

Food supply shocks are increasing worldwide, urging discovery of methods to manage the risk of food shock and boost food supply chain resilience. Ecological theory suggests that network structure is crucial for the resilience of the food supply chain. Here we show that boosting a city’s food supply chain diversity increases the resistance of a city to food shocks of mild to moderate severity up to 15%. We develop an intensity-duration-frequency model linking food shock risk to supply chain diversity. The empirical-statistical model is based on annual food inflow observations from all metropolitan areas in the United States during the years 2012-2015, years when most of the country experienced moderate to severe droughts. This model is simple, operationally useful, and hazard-agnostic. Using this method cities can improve their resistance to food supply shocks with policies that increase the food supply chain’s diversity.
The Loss of DLG2 Isoform 7/8, But Not Isoform 2, is Critical in Advanced Staged Neuroblastoma
Authors: Keane Simon , Martinsson Tommy , Kogner Per , Ejeskar Katarina
Published: October 2020

BACKGROUND: Neuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling. METHODS: We evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available neuroblastoma data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS.RESULTS: In neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability.CONCLUSION: We have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.
Hypoproliferative human NPC xenografts survived extendedly in the brain of immunocompetent rats
Authors: Liu Chunhua , Wang Xiaoyun , Huang Wenhao , Meng Wei , Su Zhenghui , Xing Qi , Shi Heng , Zhang Di , Zhou Min , Zhao Yifan , Wang Haitao , Pan Guangjin , Zhong Xiaofen , Pei Duanqing , Guo Yiping
Published: October 2020

Background: There is a huge controversy about whether xenograft or allograft in the “immune-privileged” brain needs immunosuppression. In animal studies, prevailing sophiscated immunosuppression or immunodeficiency is detrimental for the recipients, which results in short lifespan of animals, and confounds functional behavioral readout of the graft benefit, discouraging long-term follow-up. Methods: Neuron-restricted human neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages and then transplanted into the brain of immunocompetent rats without use of immunosuppressant. The graft survivals, their cell fates and HLA expression levels were examined over time (up to months after transplantation). We compared the survival capability of NPCs from different passages, and in different transplantation sites (brain parenchyma vs. para-and intra-ventricular sites). The host responses to the grafts were also investigated.Results: Our results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat cerebro-parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA expression level and host MHC-II expression level remain relatively low and little change over the long-term survival, and therefore can’t predict the late-onset rejection. Human grafts in or close to cerebroventricle are more vulnerable to the immune attack than the intra-striatum grafts. Prevention of graft hyperplasia by using hypoproliferative late-passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood–brain barrier (BBB). Conclusions: The present study confirms the “immune privilege” of the brain parenchyma, and more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.