bluuebunny/crossref_metadata_2025_split huggingface dataset:
ClustALL: A robust clustering strategy for stratification of patients with acutely decompensated cirrhosis
Authors: Palomino-Echeverria Sara , Huergou Estefania , Ortega-Legarre Asier , Uson Eva M. , Aguilar Ferran , de la Pena Carlos , Lopez-Vicario Cristina , Alessandria Carlo , Laleman Wim , Queiroz Alberto Farias , Moreau Richard , Fernandez Javier , Arroyo Vicente , Caraceni Paolo , Lagani Vincenzo , Sanchez Cristina , Claria Joan , Tegner Jesper , Trebicka Jonel , Kiani Narsis , Planell Nuria , Rautou Pierre-Emmanuel , Gomez-Cabrero David 
Published: November 2023

AbstractPatient heterogeneity represents a significant challenge for both individual patient management and clinical trial design, especially in the context of complex diseases. Most existing clinical classifications are based on scores built to predict patients’ outcomes. These classical methods may thus miss features that contribute to heterogeneity without necessarily translating into prognostic implications.To address patient heterogeneity at hospital admission, we developed ClustALL, a computational pipeline designed to handle common clinical data challenges such as mixed data types, missing values, and collinearity. ClustALL also facilitates the unsupervised identification of multiple and robust stratifications. We applied ClustALL to a prospective European multicentre cohort of patients with acutely decompensated cirrhosis (AD) (n=766), a highly heterogeneous disease. ClustALL identified five robust stratifications for patients with AD, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features but also having a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n=580).In conclusion, this study developed ClustALL, a novel and robust stratification method capable of addressing challenges tied to intricate clinical data and applicable to complex diseases. By applying ClustALL to patients with AD, we identified three patient clusters, offering insights that could guide future clinical trial design.
Superbugs online: Co-production of an educational website to increase public understanding of the microbial world in, on and around us
Authors: Tyrrell Jon M. , Hatch Sarah , Flanagan Melissa , Owen Kerry , Proctor Yvonne , Stone Catherine , Fricker Geoff , Hullis Kirk , Eberl Matthias 
Published: November 2023

1.AbstractDigital tools and online presence have become a cornerstone to public engagement and involvement strategy and delivery. We here describe the co-production process behind launching a new multilingual resource for schools in the UK and beyond, jointly between university scientists, engagement professionals, primary and secondary teachers, and web designers. The ‘Superbugs’ website aims at raising awareness and increasing public understanding of the microbial world in, on and around us, and has attracted >19,000 online visitors, >33,500 page views and >775,000 Twitter impressions over the past 24 months.Superbugs.onlineis available in English, Welsh, Irish and Scottish Gaelic, thus making it accessible to everyone in the UK and Ireland, regardless of the language in which they receive and deliver their science education. The website is easy to navigate and features background information, quizzes, animations, videos, illustrated stories, interactive timelines, games and protocols for home experiments. All materials are presented in a non-prescriptive way, aimed at allowing flexibility for the materials to be adapted to the individual needs of teachers and pupils alike. Our work has led to demonstrable impact on the co-production team and on pupils and teachers as key stakeholders, based on a comprehensive evaluation of the co-production process itself, the impact of the end product, and the creation of lasting relationships with stakeholders and co-producers, for the mutual benefit of everyone involved.2.Data summaryThe authors confirm all supporting data have been provided within the article or through supplementary data files.
Suppressing DNMT3a Alleviates the Intrinsic Epigenetic Barrier for Optic Nerve Regeneration and Restores Vision in Adult Mice
Authors: Tai Wai Lydia , Cho Kin-Sang , Kriukov Emil , Ashok Ajay , Wang Xuejian , Monavarfeshani Aboozar , Yan Wenjun , Li Yingqian , Guan Timothy , Sanes Joshua R. , Baranov Petr , Chen Dong Feng 
Published: November 2023

ABSTRACTThe limited regenerative potential of the optic nerve in adult mammals presents a major challenge for restoring vision after optic nerve trauma or disease. The mechanisms of this regenerative failure are not fully understood1,2. Here, through small-molecule and genetic screening for epigenetic modulators3, we identify DNA methyltransferase 3a (DNMT3a) as a potent inhibitor of axon regeneration in mouse and human retinal explants. Selective suppression of DNMT3a in retinal ganglion cells (RGCs) by gene targeting or delivery of shRNA leads to robust, full-length regeneration of RGC axons through the optic nerve and restoration of vision in adult mice after nerve crush injury. Genome-wide bisulfite and transcriptome profiling in combination with single nucleus RNA-sequencing of RGCs revealed selective DNA demethylation and reactivation of genetic programs supporting neuronal survival and axonal growth/regeneration by DNMT3a deficiency. This was accompanied by the suppression of gene networks associated with apoptosis and inflammation. Our results identify DNMT3a as the central orchestrator of an RGC-intrinsic mechanism that limits optic nerve regeneration. Suppressing DNMT3a expression in RGCs unlocks the epigenetic switch for optic nerve regeneration and presents a promising therapeutic avenue for effectively reversing vision loss resulted from optic nerve trauma or diseases.
Ten years malaria trend analysis in Mangili Public Health Centre, East Sumba District of East Nusa Tenggara Province, Indonesia: a retrospective study
Authors: Lobo Maria , Guntur Robertus Dole , Kusumaningrum Damai , Bria Yulianti Paula 
Published: November 2023

AbstractBACKGROUNDMalaria still remains a major public health problem globally including in Indonesia. Currently, most of malaria cases are in the eastern part of the country. However, there is no information yet regarding the trends of malaria prevalence at rural health institution particularly at Mangili Public Health Centre.AIMThis study aims to explore the trend of malaria prevalence over a ten-year period.METHODSA retrospective study was carried out in the Centre. The laboratory record books from January 2013 to December 2022 were carefully reviewed to identify malaria cases based on the sex, age, type of plasmodium, year and month when the patients diagnosed malaria microscopically. The trend analysis was applied to identify the trend of malaria over the period under review.RESULTSOver the last ten years, 19,938 blood films were requested for malaria diagnosis at the health centre. From this number, 3.679 (18.5%, with 95% confidence interval (CI): 17.2 – 19.7) were microscopically confirmed malaria cases. From the total cases, prevalence of plasmodium falciparum, vivax and mix infection was 85.5% with 95% CI: 84.3 – 86.8; 6.39% with 95% CI: 3.26 – 9.51; and 7.58% with 95% CI: 4.48 – 10.7 respectively. The number of malaria cases reached a peak in January, whilst it was the lowest in October. Overall trend on the prevalence of malaria decreased significantly, however the prevalence of plasmodium falciparum increased considerably during COVI-19 pandemic. The prevalence of plasmodium falciparum, vivax and mixed infection was higher in male, age group ≥ 15, and student than their counterpart.CONCLUSIONMalaria remains high in this area with plasmodium falciparum is the dominant species followed by mixed infection. Scaling up malaria control and prevention activities are very crucial to significantly reduce the burden of malaria and to boost malaria elimination in this region.
Endophytic bacterial communities of alpine Rosaceae plants are affected by the plant tissue, collection site and host plant and culturable psychrotolerant isolates contribute to plant freezing stress tolerance
Authors: Marian Malek , Antonielli Livio , Pertot Ilaria , Perazzolli Michele 
Published: November 2023

SummaryWild plants growing in alpine regions are associated with endophytic microbial communities that may support plant growth and survival under cold conditions.The structure and function of endophytic bacterial communities were characterised in flowers, leaves and roots of three alpine Rosaceous plants in Alpine areas using a combined amplicon sequencing and culture-dependent approach to identify factors shaping these communities.Amplicon-sequencing analysis revealed that plant tissue, collection site and host plant are the main factors affecting the richness, diversity and taxonomic structure of endophytic bacterial communities in alpine Rosaceae plants. Core endophytic bacterial taxa were identified as 31 amplicon sequence variants highly prevalent across all plant tissues.Psychrotolerant bacterial endophytes belonging to the core taxa ofDuganella, Erwinia, PseudomonasandRhizobiumgenera mitigated freezing stress in strawberry plants, demonstrating the beneficial role of endophytic bacterial communities and their potential use for cold stress mitigation in agriculture.
UNLOCKING ROBOTIC POTENTIAL THROUGH MODERN ORGAN SEGMENTATION
Authors: Chaudhary Ansh 
Published: November 2023

AbstractDeep learning has revolutionized the approach to complex data-driven problems, specifically in medical imaging, where its techniques have significantly raised efficiency in organ segmentation. The urgent need to enhance the depth and precision of organ-based classification is an essential step towards automation of medical operation and diagnostics. The research aims to investigate the effect and potential advantages transformer models have on binary semantic segmentation, the method utilized for the project. Hence, I employed the SegFormer model, for its lightweight architecture, as the primary deep learning model, alongside the Unet. A custom 2D computerized tomography (CT) scan dataset was assembled, CT-Org2D through meticulous operations. Extensive experiments showed that, in contrast to the selected models, the task’s simplicity required a redesigned Unet architecture with reduced complexity. This model yielded impressive results: Precision, Recall, and IOU scores of 0.91, 0.92, and 0.85 respectively. The research serves as a starting point, motivating further exploration, through different methodologies, to achieve even greater efficiency in organ segmentation.
Environment-independent distribution of mutational effects emerges from microscopic epistasis
Authors: Ardell Sarah , Martsul Alena , Johnson Milo S. , Kryazhimskiy Sergey 
Published: November 2023

AbstractPredicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recently discovered global epistasis, where the fitness effects of mutations scale with the fitness of the background genotype, can improve predictions, but how the environment modulates this scaling is unknown. We measured the fitness effects of ∼100 insertion mutations in 42 strains ofSaccharomyces cerevisiaein six laboratory environments and found that the global-epistasis scaling is nearly invariant across environments. Instead, the environment tunes one global parameter, the background fitness at which most mutations switch sign. As a consequence, the distribution of mutational effects is predictable across genotypes and environments. Our results suggest that the effective dimensionality of genotype-to-phenotype maps across environments is surprisingly low.One Sentence SummaryThe effects of mutations on microbial growth rate follow a pattern of global epistasis that is invariant across environments.
CAnDI: a new tool to investigate conflict in homologous gene trees and explain convergent trait evolution
Authors: Robertson Holly M. , Walker Joseph F. , Moyroud Edwige 
Published: November 2023

AbstractPhenotypic convergence is found across the tree of life, and morphological similarities in distantly related species are often presumed to have evolved independently. However, clarifying the origins of traits has recently highlighted the complex nature of evolution, as apparent convergent features often share similar genetic foundations. Hence, the tree topology of genes that underlie such traits frequently conflicts with the overall history of species relationships. This conflict creates both a challenge for systematists and an exciting opportunity to investigate the rich, complex network of information that connects molecular trajectories with trait evolution. Here we present a novel conflict identification program named CAnDI (Conflict And Duplication Identifier), which enables the analysis of conflict in homologous gene trees rather than inferred orthologs. We demonstrate that the analysis of conflicts in homologous trees using CAnDI yields more comparisons than in ortholog trees in six datasets from across the eukaryotic tree of life. Using the carnivorous trap of Caryophyllales, a charismatic group of flowering plants, as a case study we demonstrate that analysing conflict on entire homolog trees can aid in inferring the genetic basis of trait evolution: by dissecting all gene relationships within homolog trees, we find genomic evidence that the molecular basis of the pleisiomorphic mucilaginous sticky trap was likely present in the ancestor of all carnivorous Caryophyllales. We also show that many genes whose evolutionary trajectories group species with similar trap devices code for proteins contributing to plant carnivory and identify aLATERAL ORGAN BOUNDARY DOMAINtranscription factor as a possible candidate for regulating sticky trap development.
An organic extract from ascidianCiona robustainduces cytotoxic autophagy in human malignant cell lines
Authors: Gallo Alessandra , Penna Ylenia Maria , Russo Maria , Rosapane Marco , Tosti Elisabetta , Russo Gian Luigi 
Published: November 2023

AbstractThe last decades have seen an increase in the isolation and characterization of anticancer compounds derived from marine organisms, especially invertebrates, and their use in clinical trials. In this regard, ascidians, which are included in the subphylum Tunicata, represent successful examples with two drugs, Aplidine© and Yondelis©, that reached the market as orphan drugs against several malignancies. Here, we report that an organic extract prepared from homogenized tissues of the Mediterranean ascidianCiona robustainhibited cell proliferation in HT-29, Hep G2, and U2 OS human cells with the former resulting as the most sensitive to the extract (EC50= 250 µg/ml). We demonstrated that the ascidian organic extract was not cytotoxic on HT-29 cells induced to differentiate with sodium butyrate, suggesting a preference for the mixture for the malignant phenotype. Finally, we reported that the cell death induced by the organic extract was mediated by the activation of a process of cytotoxic autophagy as a result of the increased expression of the LC3-II marker and the number of autophagic vacuoles, which almost doubled in treated HT-29 cells. In summary, although the detailed chemical composition of theCiona robustaextract is still undetermined, our data suggest the presence in it of bioactive compounds possessing anticancer activity.
The Lifeact-EGFP Quail: A New Avian Model For Studying Actin DynamicsIn Vivo
Authors: Alvarez Yanina D. , van der Spuy Marise , Wang Jian Xiong , Noordstra Ivar , Tan Siew Zhuan , Carroll Murron , Yap Alpha S. , Serralbo Olivier , White Melanie D. 
Published: November 2023

AbstractHere we report the generation of a transgenic Lifeact–EGFP quail line for the investigation of actin organization and dynamics during morphogenesisin vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviours and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we reveal the dynamics of cells undergoing apical constriction and the emergence of large-scale actin structures such as supracellular cables and rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact–EGFP transgenic quail as a new model system for livein vivoinvestigations of the actin cytoskeleton.
STRANDS OF CONNECTION: LIVESTOCK GRAZING, VEGETATION DENSITY, AND ORB-WEAVER SPIDER PERSISTENCE
Authors: Oyarzabal Guilherme , Guimarães Murilo 
Published: November 2023

AbstractStudies on the effects of grazing disturbances in grasslands have shown mixed results for spider diversity, mainly regarding their guilds. While ungrazing, low, and moderate grazing potentially enhance diversity of orb-weavers, heavy grazing seems to reduce specieś richness. On the population level, studies of orb-weavers are scarce, and the effects of grazing are unknow. In this way, we investigated the effects of different levels of grazing on population persistence of orb-weaver spiders, hypothesizing that low to intermediate disturbances benefit populations. We predict that high grazing, due to the removal of vegetation structure, will negatively affect occupancy and abundance of orb-weavers. For that, we experimentally controlled grazing pressure and obtained population occurrence and counts of two orb-weaver spider species,Argiope argentataandAlpaida quadrilorata. We found thatA. argentatawas directly affected by grazing, as it relies on higher vegetation for web-building. In contrast,A. quadrilorata, which occurs in cattle-resistant rosette plants, showed no effects of grazing.Implications for insect conservation:Our study emphasizes the need for balanced grazing practices and habitat conservation to protect orb-weaver spiders and other arthropods, as well as, species-specific effects for species from the same guild, underscoring their ecological significance in maintaining ecosystem stability.
Self-reported decreases in the purchases of selected unhealthy foods resulting from the implementation of warning labels in Mexican youth and adult population
Authors: Contreras-Manzano Alejandra , White Christine M. , Nieto Claudia , Quevedo Kathia L. , Vargas-Meza Jorge , Hammond David , Thrasher James F. , Barquera Simón , Jáuregui Alejandra 
Published: November 2023

AbstractBackgroundFront-of-package nutritional warning labels (WLs) are designed to facilitate identification and selection of healthier food choices. We assessed self-reported changes in purchasing different types of unhealthy foods due to WLs in Mexico and the association between the self-reported reductions in purchases of sugary beverages and intake of water and sugar-sweetened beverages.MethodsData came from 14-17 year old youth (n=1,696) and adults ≥18 (n=7,775) who participated in the Mexican arm of the 2020-2021 International Food Policy Study, an annual repeat cross-sectional online survey. Participants self-reported whether the WLs had influenced them to purchase less of each of ten unhealthy food categories due to WLs. Among adults, a 23-item Beverage Frequency Questionnaire was used derive past 7-day intake of water and sugary beverages analyzed to determine the relationship between self-reported reductions in purchasing sugary drinks due to the WLs. Multilevel mixed-effects logistic regression models were fitted to estimate the percentage of participants who self-reported reducing purchases within each food group, and overall. Sociodemographic characteristics associated with this reduction were investigated as well.ResultsOverall, 44.8% of adults and 38.7% of youth reported buying less of unhealthy food categories due to the implementation of WL, with the largest proportion reporting decreased purchases of cola, regular and diet soda. A greater impact of WLs on the reported purchase of unhealthy foods was observed among the following socio-demographic characteristics: females, individuals who self-identified as indigenous, those who were overweight, individuals with lower educational levels, those with higher nutrition knowledge, households with children, and those with a significant role in household food purchases. In addition, adults who reported higher water intake and lower consumption of sugary beverages were more likely to report reduced purchases of sugary drinks due to the WLs. Adults who reported greater water intake and lower sugary beverages intake were significantly more likely to report buying fewer sugary drinks due to the WLs.ConclusionOur findings suggest that implementation of WLs has reduced purchases of unhealthy foods in Mexico. These results underscore the positive impact of the labeling policy particularly in subpopulations with lower levels of education and among indigenous adults.
Epigenetic and transcriptional regulation of the human angiotensinogen gene by high salt
Authors: Perla Sravan , Kumar Ashok 
Published: November 2023

AbstractHypertension is caused by a combination of genetic and environmental factors. Angiotensinogen (AGT) is a component of RAAS, that regulates blood pressure. The human angiotensinogen (hAGT) gene has -6A/-6G polymorphism and -6A variant is associated with human hypertension. In this study, we have investigated the epigenetic regulation of the hAGT. To understand transcriptional regulation of the hAGT, we have made transgenic animals containing -6A. We show that HS affects DNA methylation and modulates transcriptional regulation of this gene in liver and kidney. High salt (HS) increases hAGT gene expression in -6A TG mice. We have observed that the number of CpG sites in the hAGT promoter is decreased after HS treatment. In the liver, seven CpG sites are methylated whereas after HS treatment, only three CpG sites remain methylated. In the kidney, five CpG sites are methylated, whereas after HS treatment, only three CpG sites remain methylated. These results suggest that HS promotes DNA demethylation and increasing AGT gene expression. RT-PCR and immunoblot analysis show that hAGT gene expression is increased by HS. Chip assay has shown that transcription factors bind strongly after HS treatment. RNA-Seq identified differentially expressed genes, novel target genes associated with hypertension, top canonical pathways, upstream regulators. One of the plausible mechanisms for HS induced up-regulation of the hAGT gene is through IL-6/JAK/STAT3/AGT axis.