bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subtle white matter intensity changes on FLAIR imaging in patients with ischemic stroke
Authors: Cougo Pedro , Colares Heber , Farinhas João Gabriel , Hämmerle Mariana , Neves Pedro , Bezerra Raquel , Balduíno Alex , Wu Ona , Pontes-Neto Octavio M. 
Published: May 2023

AbstractBackgroundThere is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities which characterize leukoaraiosis are present within regions of normal-appearing white matter. In this study, we aimed to verify whether signal intensity on FLAIR imaging in normal-appearing white matter is related to the leukoaraiosis burden.MethodsWe performed a cross-sectional study of adult patients admitted with a diagnosis of acute ischemic stroke or transient ischemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, white matter was further segmented based on voxel-distance from leukoaraiosis borders. Normalized mean FLAIR signal intensity on normal-appearing white matter (NAWMM) was used as a dependent variable in univariate and multivariate statistical analysis, and leukoaraiosis volume quartiles (LKAV) and clinical data as independent variables.ResultsOne-hundred consecutive patients were selected for analysis (53% female, mean age 68 years). NAWMMwas higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. NAWMMwas independently associated with leukoaraiosis volume. In voxels in the vicinity of leukoaraiosis borders, there was a linear association between LKAVand NAWMM(B=0.03;P<0.01). In voxels non-adjacent to leukoaraiosis borders, there was a non-linear association, with higher values of NAWMMamong patients in the second and third quartiles, and lower in the first and fourth quartiles (B=-0.21 for the second order term;P<0.01). In multivariate analysis, leukoaraiosis was the only variable independently related to NAWMM.ConclusionsOur results show that normal-appearing white matter exhibits subtle signal intensity changes that are related to leukoaraiosis burden. The neuroimaging signature of these subtle changes suggests that they might not be a milder form of leukoaraiosis, but rather rather reflect widespread etiopathogenic processes underlying small-vessel disease and thus, leukoaraiosis development.
DrosophilaAHR limits tumor growth and stem cell proliferation in the intestine
Authors: Tsai Minghua , Sun Jiawei , Alexandre Cyrille , Shapiro Michael , Franchet Adrien , Li Ying , Gould Alex P. , Vincent Jean-Paul , Stockinger Brigitta , Diny Nicola Laura 
Published: May 2023

AbstractThe aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, theDrosophilahomolog of AHR, has only been studied in the context of development but not in the adult intestine. Here, we show thatspinelessis upregulated in the adult intestinal epithelium after infection withPseudomonas entomophila(P.e.). Spineless knockdown increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using eitherNotchRNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism. These findings demonstrate a new role for Spineless in the adultDrosophilamidgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium.
The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs
Authors: Murray Gemma G. R. , Hossain A. S. Md. Mukarram , Miller Eric L. , Bruchman Sebastian , Balmer Andrew J. , Matuszewska Marta , Herbert Josephine , Hadjirin Nazreen F. , Mugabi Robert , Li Ganwu , Ferrando Maria Laura , Fernandes de Oliveira Isabela Maria , Nguyen Thanh , Yen Phung L. K. , Phuc Ho D. , Moe Aung Zaw , Wai Thiri Su , Gottschalk Marcelo , Aragon Virginia , Weigand Peter Valentin- , Heegaard Peter M. H. , Vrieling Manouk , Maw Min Thein , Myint Hnin Thidar , Win Ye Tun , Hoa Ngo Thi , Bentley Stephen D. , Clavijo Maria J. , Wells Jerry M. , Tucker Alexander W. , Weinert Lucy A. 
Published: May 2023

AbstractThe expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species this can affect the health of humans as well as livestock. Here we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis ofStreptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages ofS. suisemerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation ofS. suisand acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential ofS. suisis yet to be fully realised.
Characterisation of the genetic determinants of context specific DNA methylation in primary monocytes
Authors: Gilchrist James J. , Fang Hai , Danielli Sara , Tomkova Marketa , Nassiri Isar , Ng Esther , Tong Orion , Taylor Chelsea , Al Mossawi Hussein , Lau Evelyn , Neville Matt , Schuster-Boeckler Benjamin , Knight Julian C. , Fairfax Benjamin P. 
Published: May 2023

AbstractDNA methylation (DNAm) has pervasive effects on gene expression and associations with ageing-related traits. Here we describe monocyte DNAm responses to inflammatory stimuli across 192 individuals. We find that, unlike the similarly widespread changes in gene expression elicited by LPS and IFNγ, DNAm is markedly more sensitive to LPS. Exposure to LPS caused differential methylation at 20,858 immune-modulated CpGs (imCpGs) which display distinct genomic localisation and transcription factor usage, dependent upon whether methylation is lost or gained. Demethylated imCpGs are profoundly enriched for enhancers, and are over-represented by genes implicated in human diseases, most notably cancer. We find LPS-induced demethylation follows hydroxymethylation and for most sites the degree of demethylation correlates with baseline signal. Notably, we find LPS exposure triggers gain in epigenetic age by approximately 6 months, identifying a potential cause of accelerated epigentic aging which has diverse negative health associations. Finally, we explore the effect of genetic variation on LPS-induced changes in DNAm, identifying 209 imCpGs under genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of human disease associated loci that also modulate imCpG formation.In summary, our findings suggest innate immune activity continually remodels DNAm in a highly punctate, enhancerenriched fashion that is under tight genetic control and predominantly involves genes commonly mutated in cancer.
Identification of dynamical changes of rabies transmission under quarantine: community-based measures towards rabies elimination
Authors: Rysava Kristyna , Tildesley Michael J. 
Published: May 2023

AbstractQuarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.Author summaryCanine rabies remains a human health risk in many countries around the world, particularly in lower and middle income settings where many dogs are free roaming and able to interact more easily with other dogs and humans. In this paper, we present results from a mathematical model that simulates the spread of rabies both between dogs and from dogs to humans and investigate the impact of quarantine and vaccination at reducing transmission. Our work demonstrates the effectiveness of quarantining both infected and exposed dogs - we observe that quarantine can have a substantial effect on reducing the number of new animals subsequently infected and thereby lowering the risk of humans being exposed to infection. Such a policy can have significant benefits, particularly in settings where access to vaccinations is challenging and resources are limited. Our research can therefore help to inform policy makers in countries where canine rabies is circulating to develop appropriate strategies to reduce the human health risks associated with canine rabies in the future.
Subchronic Toxicity Assessment of Perfluoroalkyl Substances by Mixed Exposure of Nine Substances at Daily Intake Relevant Concentration
Authors: Takeda Kazuki , Saito Taki , Sasaki Sakura , Eguchi Akifumi , Sugiyama Makoto , Suzuki Kio , Eto Saeka , Kamata Ryo 
Published: May 2023

AbstractPer- and poly-fluoroalkyl substances (PFAS) have been utilized extensively for various applications owing to their distinctive chemical properties. They exhibit high persistence in the environment and accumulate within the human body, necessitating toxicity assessments. However, the consequences of prolonged, low-level exposure to PFAS and concurrent exposure to multiple PFAS have not been explored. In this study, male C57BL/6J mice (aged 8 weeks) were exposed to a composite of nine PFAS, which include long-chain PFAS (e.g. perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g. perfluorobutanoic acid and perfluorobutanesulfonic acid) at concentrations equivalent to the estimated daily human intake in the composition reported (1 µg/L [sum of the nine compounds], the maximum reported exposure concentration) via drinking water. Histological examination revealed vacuolization of hepatocytes and irregular arrangement of hepatocyte cords, suggesting that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, and in addition to known substances such as glutathione, a compound with unknown biological function; 2,5-dihydro-2,4-dimethyloxazole was found. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism-and cancer-related genes as well as phospholipid metabolism. Future studies are required to evaluate the chronic toxicity of prolonged, low-level exposure to PFAS mixtures and to investigate the health effects of PFAS.
labelSeg: segment annotation for tumor copy number alteration profiles
Authors: Zhao Hangjia , Baudis Michael 
Published: May 2023

1AbstractSomatic copy number alterations (SCNA) are a predominant type of oncogenomic alterations that affect a large proportion of the genome in the majority of cancer samples. Current technologies allow high-throughput measurement of such copy number aberrations, generating results consisting of frequently large sets of SCNA segments. However, the automated annotation and integration of such data are particularly challenging because the measured signals reflect biased, relative copy number ratios. In this study, we introducelabelSeg, an algorithm designed for rapid and accurate annotation of CNA segments, with the aim of enhancing the interpretation of tumor SCNA profiles. Leveraging density-based clustering and exploiting the length-amplitude relationships of SCNA, our algorithm proficiently identifies distinct relative copy number states from individual segment profiles. Its compatibility with most CNA measurement platforms makes it suitable for large-scale integrative data analysis. We confirmed its performance on both simulated and sample-derived data from The Cancer Genome Atlas (TCGA) reference dataset, and we demonstrated its utility in integrating heterogeneous segment profiles from different data sources and measurement platforms. Our comparative and integrative analysis revealed common SCNA patterns in cancer and protein-coding genes with a strong correlation between SCNA and mRNA expression, promoting the investigation into the role of SCNA in cancer development.
WITHDRAWN: Cholesterol mechanically stabilizes aquaporin-0 arrays by strengthening the association of adjacent tetramers
Authors: Orjuela Juan D. , Chiu Po-Lin , Walz Thomas , de Groot Bert L. , Aponte-Santamaría Camilo 
Published: May 2023

Withdrawal StatementThe authors have withdrawn this manuscript owing to its merge with BIORXIV/2023/540959. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The merged preprint can be found atdoi.org/10.1101/2023.05.16.540959
Metabolic, Biochemical, Mineral and Fatty acid profiles of edibleBrassicaceaemicrogreens establish them as promising functional food
Authors: Pant Yogesh , Lingwan Maneesh , Masakapalli Shyam Kumar 
Published: May 2023

AbstractHidden hunger due to micronutrient deficiencies affecting one in three people is a global concern. Identifying functional foods which provide vital health beneficial components in addition to the nutrients is of immense health relevance. Microgreens are edible seedlings enriched with concentrated minerals and phytochemicals whose dietary potential as functional foods needs evaluation. In this study, comprehensive biochemical, mineral, metabolic, and fatty acid profiles of fourBrassicaceaemicrogreens - mustard (Brassica juncea), pak choi (Brassica rapa subsp. chinensis), radish pink (Raphanus sativus), and radish white (Raphanus ruphanistrum) was investigated. The biochemical and mineral profiling confirmed their promising nutritional and antioxidant nature and as excellent sources of minerals. Mineral profiling using inductively coupled plasma mass spectrometry (ICP-MS) exhibited promising levels of Fe, Mn, Mg, K, and Ca in microgreens. Gas chromatography-mass spectrometry (GC-MS) based metabolite profiling highlighted a range of phytochemicals-sugars, amino acids, organic acids, amines, fatty acids, phenol, and other molecules. Fatty acid profiling established promising levels of Oleic acid (C18:1; Monounsaturated fatty acids-MUFA) and linoleic acids (C18:2; omega-6 Poly unsaturated fatty acid-PUFA), which are health beneficial. It is estimated that fresh microgreens (100 g) can meet about 20 % to 50 % recommended dietary allowance (RDA) of macro- and micro-minerals along with providing useful fatty acids and antioxidants. Overall, the study highlightedBrassicaceaemicrogreens as an excellent nutrient source that can act as functional foods with promising potential to overcome “hidden hunger”.Graphical AbstractHighlightsBrassicaceaemicrogreens are rich in molecules with relevance to nutrition and healthThe biochemical analysis supported the antioxidant nature of microgreensComprehensive metabolite profiles of edible microgreens ofBrassica juncea(Mustard),Brassica rapa subsp. chinensis(Pak Choi),Raphanus sativus(Radish Pink), andRaphanus ruphanistrum(Radish white) using GC-MS are reportedIonomics analysis using theBrassicaceaemicrogreens exhibited promising levels of microminerals Fe, Mn, Mg, K, and CaFatty acid profiles show promising levels of Linoleic acid and Oleic acid, which have health relevance
Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion-Volumetric Printing of Microgels
Authors: Ribezzi Davide , Gueye Marième , Florczak Sammy , Dusi Franziska , de Vos Dieuwke , Manente Francesca , Hierholzer Andreas , Fussenegger Martin , Caiazzo Massimiliano , Blunk Torsten , Malda Jos , Levato Riccardo 
Published: May 2023

ABSTRACTIn living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and therefore a bottleneck towards creating physiologically relevant models. Addressing this limitation, we introduced a novel technique, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing to spatially pattern multiple inks/cell types. Light-responsive microgels were developed as permissive microenvironment for cell homing and self-organization, and as bioresins (µResins) for light-based bioprinting. Tuning the mechanical and optical properties of these gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. µResins can then be sculpted within seconds with tomographic light projections into centimetre-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids within microgels enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP was applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with enhanced functionality, and for developing engineered living systems and (metabolic) disease models.
Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets
Authors: Ramanan Deepshika , Chowdhary Kaitavjeet , Candéias Serge M. , Sassone-Corsi Martina , Mathis Diane , Benoist Christophe 
Published: May 2023

ABSTRACTFoxp3+regulatory T cells (Tregs) in the colon are key to promoting peaceful co-existence with symbiotic microbes. Differentiated in either thymic or peripheral locations, and modulated by microbes and other cellular influencers, colonic Treg subsets have been identified through key transcription factors (TF; Helios, Rorg, Gata3, cMaf), but their inter-relationships are unclear. Applying a multimodal array of immunologic, genomic, and microbiological assays, we find more overlap than expected between populations. The key TFs play different roles, some essential for subset identity, others driving functional gene signatures. Functional divergence was clearest under challenge. Single-cell genomics revealed a spectrum of phenotypes between the Helios+ and Rorγ+ poles, different Treg-inducing bacteria inducing the same Treg phenotypes to varying degrees, not distinct populations. TCR clonotypes in monocolonized mice revealed that Helios+ and Rorγ+ Tregs are related, and cannot be uniquely equated to tTreg and pTreg. We propose that rather than the origin of their differentiation, tissue-specific cues dictate the spectrum of colonic Treg phenotypes.
Investigating the Volume and Diversity of Data Needed for Generalizable Antibody-Antigen ∆∆G Prediction
Authors: Hummer Alissa M. , Schneider Constantin , Chinery Lewis , Deane Charlotte M. 
Published: May 2023

AbstractAntibody-antigen binding affinity lies at the heart of therapeutic antibody development: efficacy is guided by specific binding and control of affinity. Here we present Graphinity, an equivariant graph neural network architecture built directly from antibody-antigen structures that achieves state-of-the-art performance on experimental ∆∆G prediction. However, our model, like previous methods, appears to be overtraining on the few hundred experimental data points available. To test if we could overcome this problem, we built a synthetic dataset of nearly 1 million FoldX-generated ∆∆G values. Graphinity achieved Pearson’s correlations nearing 0.9 and was robust to train-test cutoffs and noise on this dataset. The synthetic dataset also allowed us to investigate the role of dataset size and diversity in model performance. Our results indicate there is currently insufficient experimental data to accurately and robustly predict ∆∆G, with orders of magnitude more likely needed. Dataset size is not the only consideration – our tests demonstrate the importance of diversity. We also confirm that Graphinity can be used for experimental binding prediction by applying it to a dataset of>36,000 Trastuzumab variants.
SCN9A: Proposal of Voltage-Gated Ion Channels as a Novel Diagnostic Marker for Alzheimer’s Disease
Authors: Shah Divyash , Shah Raehash , Waldron Alyssa , Leonardi Donna 
Published: May 2023

AbstractAlzheimer’s disease (AD) is an age-related neurodegenerative disease that affects over 6 million adults each year. As individuals age, their cells do not repair themselves which leads to proliferation arrest known as senescence. In the nervous system, astrocyte senescence has been associated with neuroinflammation and other AD processes. Thus, studying senescence may be a unique approach to understanding AD pathology. This study looks at the correlation between SCN9A, a novel gene target, and AD. Results suggest SCN9A may be a potential diagnostic marker for AD. A model was created with an 80%+ accuracy rate in predicting AD. Overall, this study suggests SCN9A plays a large role in neurodegeneration and treating AD.