bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of Mifepristone and Methotrexate for the Treatment of Ectopic Pregnancy: A Systematic Review Protocol
Authors: Su Qiling , Feng Huiyan , Tian Tian , Liao Xiaoqian , Li Yunhui , Li Xiaomao 
Published: September 2021

AbstractAimThe increase in ectopic pregnancies (EP) in recent years and their impact on female fertility forces physicians to find an effective medical treatment that can avoid surgery as soon as possible. Methotrexate and mifepristone are widely used in conservative treatments, but the effectiveness of this combination is not completely clear. Therefore, the aims in this meta-analysis are to systematically analyze the efficacy of mifepristone combined with methotrexate in the treatment of EP through existing studies and draw a conclusion, to evaluate the advantages and disadvantages of inclusion trials and propose improvement measures and scientific designing schemes.MethodsSix databases will be searched, including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure(CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Database (WF). Randomized controlled trials published up to October 2020 will be selected. Search terms include mifepristone, methotrexate, EP, and random (free word/synonym expansion). We will include trials in which the experimental group was treated with combination of mifepristone and methotrexate, and the control group was treated with mifepristone alone. Revman 5.4 will be used to evaluate the quality of the trials, and the effect model will be selected to analyze the results. Cure rate will be the main outcome index.ResultOnly when we finish this meta analysis can we get the result.DiscussionThe results of this study will provide evidence for the efficacy of mifepristone combined with methotrexate therapy in the treatment of EP. The site of onset of pregnancy should be taken into account.PROSPERO registration numberCRD42021246757
Systemic and Genetic Risk Factors for Reticular Macular Disease and Soft Drusen in Age-Related Macular Degeneration
Authors: Thomson Robert J. , Chazaro Joshua , Otero-Marquez Oscar , Ledesma-Gil Gerardo , Tong Yuehong , Coughlin Arielle C. , Teibel Zachary R. , Alauddin Sharmina , Tai Katy , Lloyd Harriet , Scolaro Maria , Govindaiah Arun , Bhuiyan Alauddin , Dhamoon Mandip S. , Deobhakta Avnish , Narula Jagat , Rosen Richard B. , Yannuzzi Lawrence A. , Freund K. Bailey , Smith R. Theodore 
Published: September 2021

ABSTRACTPurposeSoft drusen and subretinal drusenoid deposits (SDD) aka reticular macular disease (RMD) characterize two pathways to advanced age-related macular degeneration (AMD). We propose these pathways are distinct diseases, with distinct genetic risks, serum risks and associated systemic diseases.Methods126 Subjects with AMD had: retinal imaging for RMD status, serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke.Results62 subjects had RMD, 64 were nonRMD (drusen only), 51 had CVD or Stroke. RMD correlated significantly with: ARMS2 risk allele (p= 0.019); lower mean serum HDL (61±18 vs. 69±22 mg/dl, p= 0.038, t test); CVD and troke (34/51 RMD, p= 0.001).NonRMD correlated/trended with APOE2 (p= 0.032) and CETP (p= 0.072) risk alleles. 97 subjects total had some drusen, which correlated with CFH risk (p= 0.016). Multivariate independent risks for RMD were: CVD and Stroke (p= 0.008), and ARMS2 homozygous risk (p= 0.038).ConclusionThe RMD and soft drusen AMD pathways have distinct systemic associations, serum and genetic risks. RMD is associated with CVD and stroke, ARMS2 risk, and lower HDL; drusen with CFH risk and two lipid risk genes. These pathways appear to be distinct diseases leading to advanced AMD.Summary StatementTwo phenotypes of age-related macular degeneration, soft drusen and reticular macular disease (the combination of subretinal drusenoid deposits and choriocapillaris insufficiency), are shown here to have distinct systemic vascular, serum, and genetic risks. These findings support the concept that these phenotypes actually represent distinct disease processes.
ChAdOx1 nCoV-19 (AZD1222) vaccine elicits monoclonal antibodies with potent cross-neutralizing activity against SARS-CoV-2 viral variants
Authors: Seow Jeffrey , Graham Carl , Hallett Sadie R. , Lechmere Thomas , Maguire Thomas J.A. , Huettner Isabella , Cox Daniel , Roberts Rebekah , Waters Anele , Ward Christopher C. , Mant Christine , Pitcher Michael J. , Spencer Jo , Fox Julie , Malim Michael H. , Doores Katie J. 
Published: September 2021

AbstractAlthough the antibody response to COVID-19 vaccination has been studied extensively at the polyclonal level using immune sera, little has been reported on the antibody response at the monoclonal level. Here we isolate a panel of 44 anti-SARS-CoV-2 monoclonal antibodies (mAbs) from an individual who received two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine at a 12-week interval. We show that despite a relatively low serum neutralization titre, mAbs with potent neutralizing activity against the current SARS-CoV-2 variants of concern (B.1.1.7, P.1, B.1.351 and B.1.617.2) were obtained. The vaccine elicited neutralizing mAbs form 8 distinct competition groups and bind epitopes overlapping with neutralizing mAbs elicited following SARS-CoV-2 infection. AZD1222 elicited mAbs are more mutated than mAbs isolated from convalescent donors 1-2 months post infection. Spike reactive IgG+ B cells were still detectable 9-months post boost. These findings give molecular insights into AZD1222 elicited antibody response.
Disentangling heterogeneity of Malignant Pleural Mesothelioma through deep integrative omics analyses
Authors: Mangiante Lise , Alcala Nicolas , Di Genova Alex , Sexton-Oates Alexandra , Gonzalez-Perez Abel , Khandekar Azhar , Bergstrom Erik N. , Kim Jaehee , Giacobi Colin , Le Stang Nolwenn , Boyault Sandrine , Cuenin Cyrille , Tabone-Eglinger Severine , Damiola Francesca , Voegele Catherine , Ardin Maude , Michallet Marie-Cecile , Soudade Lorraine , Delhomme Tiffany M. , Poret Arnaud , Brevet Marie , Copin Marie-Christine , Giusiano-Courcambeck Sophie , Damotte Diane , Girard Cecile , Hofman Veronique , Hofman Paul , Mouroux Jérôme , Lacomme Stephanie , Mazieres Julien , de Montpreville Vincent Thomas , Perrin Corinne , Planchard Gaetane , Rouquette Isabelle , Sagan Christine , Scherpereel Arnaud , Thivolet Francoise , Vignaud Jean-Michel , Jean Didier , Gilg Soit Ilg Anabelle , Olaso Robert , Meyer Vincent , Boland Anne , Deleuze Jean-Francois , Altmuller Janine , Nuernberg Peter , Lantuejoul Sylvie , Ghantous Akram , Maussion Charles , Courtiol Pierre , Hernandez-Vargas Hector , Caux Christophe , Girard Nicolas , Lopez-Bigas Nuria , Alexandrov Ludmil B. , Salle Françoise Galateau , Foll Matthieu , Fernandez-Cuesta Lynnette 
Published: September 2021

SummaryMalignant Pleural Mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Using the largest series of whole-genome sequencing data integrated with transcriptomic and epigenomic data using multi-omic factor analysis, we demonstrate that MPM heterogeneity arises from four sources of variation: tumor cell morphology, ploidy, adaptive immune response, and CpG island methylator phenotype. Previous genomic studies focused on describing only the tumor cell morphology factor, although we robustly find the three other sources in all publicly available cohorts. We prove how these sources of variation explain the biological functions performed by the cancer cells, and how genomic events shape MPM molecular profiles. We show how these new sources of variation help understand the heterogeneity of the clinical behavior of MPM and drug responses measured in cell lines. These findings unearth the interplay between MPM functional biology and its genomic history, and ultimately, inform classification, prognostication and treatment.Graphical abstract
Tuning epithelial cell-cell adhesion and collective dynamics with functional DNA-E-cadherin hybrid linkers
Authors: Schoenit Andreas , Giudice Cristina Lo , Hahnen Nina , Ollech Dirk , Jahnke Kevin , Göpfrich Kerstin , Cavalcanti-Adam Elisabetta Ada 
Published: September 2021

AbstractThe binding strength between epithelial cells is crucial for tissue integrity, signal transduction and collective cell dynamics. However, there is no experimental approach to precisely modulate cell-cell adhesion strength at the cellular and molecular level. Here, we establish DNA nanotechnology as tool to control cell-cell adhesion of epithelial cells. We designed a DNA-E-cadherin hybrid system consisting of complementary DNA strands covalently bound to a truncated E-cadherin with a modified extracellular domain. DNA sequence design allows to tune the DNA-E-cadherin hybrid molecular binding strength, while retaining its cytosolic interactions and downstream signaling capabilities. The DNA-E-cadherin hybrid facilitates strong and reversible cell-cell adhesion in E-cadherin deficient cells by forming mechanotransducive adherens junctions. We assess the direct influence of cell-cell adhesion strength on intracellular signaling and collective cell dynamics. This highlights the scope of DNA nanotechnology as a precision technology to study and engineer cell collectives.
Immune function of the serosa in hemimetabolous insect eggs
Authors: Jacobs Chris G.C. , van der Hulst Remy , Chen Yen-Ta , Williamson Ryan P. , Roth Siegfried , van der Zee Maurijn 
Published: September 2021

AbstractInsects comprise more than a million species and many authors have attempted to explain this success by evolutionary innovations. A much overlooked evolutionary novelty of insects is the serosa, an extraembryonic epithelium around the yolk and embryo. We have shown previously that this epithelium provides innate immune protection to eggs of the beetle Tribolium castaneum. It remained elusive, however, whether this immune competence evolved in the Tribolium lineage or is ancestral to all insects. Here, we expand our studies to two hemimetabolous insects, the bug Oncopeltus fasciatus and the swarming grasshopper Locusta migratoria. For Oncopeltus, RNA sequencing reveals an extensive response upon infection, including the massive upregulation of antimicrobial peptides (AMPs). We demonstrate antimicrobial activity of these peptides using in vitro bacterial growth assays, and describe two novel AMP families called Serosins and Ovicins. For both insects, qPCRs show immune competence of the eggs when the serosa is present, and in situ hybridizations demonstrate that immune gene expression is localized in the serosa. This first evidence from hemimetabolous insect eggs suggests that immune competence is an ancestral property of the serosa. The evolutionary origin of the serosa with its immune function might have facilitated the spectacular radiation of the insects.
DIDO3 acts at the interface of RNAPII transcription and chromatin structure regulation
Authors: Pons Tirso , Serra Francois , Pazos Florencio , Valencia Alfonso , Martínez-A Carlos 
Published: September 2021

ABSTRACTChromatin structure and organization has a key role in gene expression regulation. Here, we integrated ChIP-seq, RNA-seq, Hi-C, epigenetic, and cancer-related mutations data to get insight into the role of Death Inducer Obliterator gene (Dido1) in RNA pol II (RNAPII) transcription and chromatin structure regulation. Analysis of ChIP-seq data of DIDO3, the largest protein isoform ofDido1, revealed binding-sites overlap about 70% with RNAPII and H3K36me3 in the mouse genome, but also significant overlap 10-30% with Polycomb, CTCF, H3K4me3, and H3K27ac. Based on this analysis we propose that DIDO3’s PHD domain interacts with H3K36me3 posttranslational modification. Integrating multi-omics data we describe how DIDO3 potentially recruit several transcription factors, including RNAPII, and also regulates genes transcribing those same transcription factors. DIDO3 regulation of the genes traduced into proteins to which it binds puts DIDO3 in the center of intricate feedback loops. We showed, by using data from a DIDO3 mutant, that DIDO3 C-terminus is responsible for most of these transcriptional regulation, and is also implicated in other very important pathways by regulating genes encoding for Polycomb-accessory proteins, subunits of the SWI/SNF chromatin remodelling, or Set1/COMPASS chromatin modifier complexes. These multi-protein complexes control gene activation or silencing and also play a role in tumour development. DIDO3 C-terminus region and splice-site for alternative DIDO2/DIDO3 protein isoforms tended to accumulate recurrent truncating mutations identified in the TCGA Pan-Cancer dataset. We hypothesize that deregulation of DIDO3, as it happens with large epigenetic complexes and long-range interactions, leads to cell differentiation deficiency and cancer development. Overall, we propose here a molecular mechanism by which DIDO3, favour RNAPII pausing and long-range chromatin interactions.
A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model
Authors: Haskey Natasha , Ye Jiayu , Estaki Mehrbod , Verdugo Meza Andrea A. , Barnett Jacqueline A. , Yousefi Mitra , Birnie Blake W. , Gruenheid Samantha , Ghosh Sanjoy , Gibson Deanna L. 
Published: September 2021

SummaryThe Mediterranean diet (MD) is a health-promoting, moderate fat diet (~ 40% energy). It is not known if the blend of fats found in the MD contribute to the beneficial protective effects. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to isocaloric diets composed with corn oil (CO, n-6 polyunsaturated-rich), olive oil (high monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2−/− mice. The MD resulted in lower clinical and histopathological scores, and induced tolerogenic CD103+CD11b+ dendritic, Th22 and IL-17+IL-22+ cells important for intestinal barrier repair. MD also reduced attendant insulin resistance and a shift to a higher health-promoting gut microbes including Lactobacillus B. animalis and Muribaculaceae, whereas CO showed higher prevalence of mucin-degraders (Akkermansia muciniphila) and colitis promoters (Enterobacteriaceae). Our findings suggest that the MD fat blend could be recommended as a maintenance diet for colitis.
Plant neighborhood shapes diversity and reduces interspecific variation of the phyllosphere microbiome
Authors: Meyer Kyle M. , Porch Robert , Muscettola Isabella E. , Vasconcelos Ana Luisa S. , Sherman Julia K. , Metcalf C. Jessica E. , Lindow Steven E. , Koskella Britt 
Published: September 2021

AbstractMicrobial communities associated with plant leaf surfaces (i.e. the phyllosphere) are increasingly recognized for their role in plant health. While accumulating evidence suggests a role for host filtering of its microbiota, far less is known about how community composition is shaped by dispersal, including from neighboring plants. We experimentally manipulated the local plant neighborhood within which tomato, pepper, or bean plants were grown in a three-month field trial. Focal plants were grown in the presence of con- or hetero-specific neighbors (or no neighbors) in a fully factorial combination. At 30-day intervals, focal plants were harvested and replaced with a new age- and species-matched cohort while allowing neighborhood plants to continue growing. 16S community profiling revealed that the strength of host filtering effects (i.e. interspecific differences in composition) decreased over time. In contrast, the strength of neighborhood effects increased over time, suggesting dispersal from neighboring plants becomes more important as neighboring plant biomass increases. We next implemented a cross-inoculation study in the greenhouse using inoculum generated from the field plants to directly test host filtering of microbiomes while controlling for directionality and source of dispersal. This experiment further demonstrated that focal host species, the host from which the microbiome came, and in one case the donor hosts’ neighbors, contribute to variation in phyllosphere bacterial composition. Overall, our results suggest that local dispersal is a key factor in phyllosphere assembly, and that demographic factors such as nearby neighbor identity and biomass or age are important determinants of phyllosphere microbiome diversity.
PlasmidHostFinder: Prediction of plasmid hosts using random forest
Authors: Aytan-Aktug Derya , Clausen Philip TLC , Szarvas Judit , Munk Patrick , Otani Saria , Nguyen Marcus , Davis James J , Lund Ole , Aarestrup Frank M 
Published: September 2021

ABSTRACTPlasmids play a major role facilitating the spread of antimicrobial resistance between bacteria. Understanding the host range and dissemination trajectories of plasmids is critical for surveillance and prevention of antimicrobial resistance. Identification of plasmid host ranges could be improved using automated pattern detection methods, compared to homology-based methods due to the diversity and genetic plasticity of plasmids. In this study, we developed a method for predicting the host range of plasmids based on the random forest machine learning method. We trained the models with 8,519 plasmids from 359 different bacterial species per taxonomic level, where the models achieved 0.662 and 0.867 Matthews correlation coefficients at the species and order levels, respectively. Our results suggest that despite the diverse nature and genetic plasticity of plasmids, our random forest model can accurately distinguish between plasmid hosts. This tool can be used online through Center for Genomic Epidemiology (https://cge.cbs.dtu.dk/services/PlasmidHostFinder/).ImportanceAntimicrobial resistance is a global health threat to humans and animals causing high mortality and morbidity, and effectively ending decades of success in fighting against bacterial infections. Plasmids confer extra genetic capabilities to the host organisms through accessory genes, which can encode antimicrobial resistance and virulence factors. In addition to lateral inheritance, plasmids can be transferred horizontally between bacterial taxa. Therefore, detecting the host range of plasmids is crucial for understanding and predicting the dissemination trajectories of extrachromosomal genes and bacterial evolution, as well as for taking effective counter measures against antimicrobial resistance.
Pharmacogenomic study of heart failure and candesartan response from the CHARM programme
Authors: Dubé Marie-Pierre , Chazara Olympe , Lemaçon Audrey , Asselin Géraldine , Provost Sylvie , Barhdadi Amina , Perreault Louis-Philippe Lemieux , Mongrain Ian , Wang Quanli , Carss Keren , Paul Dirk S , Cunningham Jonathan W , Rouleau Jean , Solomon Scott D , McMurray John J V , Yusuf Salim , Granger Chris B , Haefliger Carolina , de Denus Simon , Tardif Jean-Claude 
Published: September 2021

ABSTRACTAimsThe Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme consisted of three parallel, randomised, double-blind clinical trials comparing candesartan with placebo in patients with heart failure (HF) categorised according to left ventricular ejection fraction and tolerability to an ACE inhibitor. We conducted a pharmacogenomic study of the CHARM studies to identify genetic predictors of heart failure progression and the efficacy and safety of treatment with candesartan.MethodsWe performed genome-wide association studies (GWAS) with the composite endpoint of cardiovascular death or hospitalisation for heart failure in 2727 patients from CHARM-Overall and stratified by CHARM study according to preserved and reduced ejection fraction. The safety endpoints were hyperkalaemia, renal dysfunction, hypotension, and change in systolic blood pressure. We also conducted a genome-wide gene-level collapsing analysis from whole-exome sequencing data with the composite cardiovascular endpoint.ResultsWe found the genetic variant rs66886237 at 8p21.3 near the gene GFRA2 to be associated with the composite cardiovascular endpoint in 1029 HF patients with preserved ejection fraction from the CHARM-Preserved study [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.55-2.35; P=1.7×10-9], but not in patients with reduced ejection fraction. None of the GWAS for candesartan safety or efficacy passed the significance threshold.ConclusionsWe have identified a candidate genetic variant potentially predictive of the progression of heart failure in patients with preserved ejection fraction. The findings require further replication and we cannot exclude the possibility that the results may be chance findings.
Transmission clusters, predominantly associated with men who have sex with men, play a main role in the propagation of HIV-1 in Northern Spain (2013-2018)
Authors: Gil Horacio , Delgado Elena , Benito Sonia , Georgalis Leonidas , Montero Vanessa , Sánchez Mónica , Cañada-García Javier E. , García-Bodas Elena , Díaz Asunción , Thomson Michael M. ,   the Spanish Group for the Study of New HIV Diagnoses
Published: September 2021

ABSTRACTViruses of HIV-1-infected individuals whose transmission is related group phylogenetically in transmission clusters (TCs). The study of the phylogenetic relations of these viruses and the factors associated with these individuals is essential to analyze the HIV-1 epidemic. In this study, we examine the role of TCs in the epidemiology of HIV-1 infection in Galicia and the Basque County, two regions of Northern Spain. A total of 1158 newly HIV-1-diagnosed patients (NDs) from both regions diagnosed in 2013-2018 were included in the study. Partial HIV-1 pol sequences were analyzed phylogenetically by approximately-maximum-likelihood with FastTree 2. In this analysis, 10,687 additional sequences from samples from HIV-1-infected individuals collected in Spain in 1999-2019 were also included to assign and determine the TCs’ sizes. TCs were defined as those which included viruses from ≥4 individuals, at least 50% of them Spaniards, and with ≥0.95 Shimodaira-Hasegawa-like node support in the phylogenetic tree. Factors associated to TCs were evaluated using odds ratios (OR) and their 95% confidence intervals (CI). Fifty one percent of NDs grouped in 162 TCs. Male patients (OR: 2.6; 95% CI: 1.5-4.7) and men having sex with men (MSM) (OR: 2.1; 95% CI: 1.4-3.2) had higher odds of belonging to a TC compared to female and heterosexual patients, respectively. Individuals from Latin America (OR: 0.3; 95% CI: 0.2-0.4), North Africa (OR: 0.4; 95% CI: 0.2-1.0), and especially Sub-Saharan Africa (OR: 0.02; 95% CI: 0.003-0.2) were inversely associated to belonging to TCs compared to native Spaniards. Differences in distribution and sizes of local TCs were observed in both regions reflecting a different epidemic pattern. Our results show that TCs play an important role in the spread of HIV-1 infection in the two Spanish regions studied, where transmission between MSM is predominant. The majority of migrants were infected with viruses not belonging to TCs that expand in Spain. Molecular epidemiology is essential to identify local peculiarities of HIV-1 propagation. The early detection of TCs and prevention of their expansion, implementing effective control measures, could reduce HIV-1 infections.