bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Butyrate on Small and Large Airways: Effects on Cell Viability, Inflammatory Changes and Permeability
Authors: Yildiz Abdullah Burak , Aksoy Gizem Tuse , Konyalilar Nur , Kayalar Ozgecan , Korkunc Seval Kubra , Bayram Hasan 
Published: February 2024

SummaryChronic airway diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma pose a significant global health burden. The pathophysiology involves chronic inflammation, with oxidative stress playing a crucial role in disease severity. Current treatments, especially for COPD, have limitations, necessitating exploration of alternative therapeutic approaches. In this study, we investigated the potential effects of butyrate, a short-chain fatty acid, on airway epithelial cells. Human bronchial epithelial cells (BEAS-2B) and bronchiolar epithelial carcinoma cells (A549) were cultured and exposed to hydrogen peroxide (H2O2) to induce oxidative stress. Butyrate was then applied at various concentrations, and the impact on cell viability, epithelial permeability, inflammatory cytokines, and gene expression was assessed. Our cell viability experiments revealed a dose-dependent reduction in viability with H2O2, while butyrate was found to be safe as it did not affect cell viability. Additionally, butyrate showed decrease in small airway permeability. Butyrate demonstrated anti- inflammatory properties, suppressing H2O2-induced release of interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF) in large airways. Gene expression analysis further highlighted complex regulatory effects of butyrate on inflammatory pathways. Our study suggests that butyrate may have potential therapeutic benefits in chronic airway diseases by modulating inflammation, permeability, and gene expression. However, further research, including in vivo studies and exploration of endogenous butyrate utilization, is needed to fully understand its pharmacodynamics and clinical relevance. Our findings contribute to the understanding of short-chain fatty acids as potential candidates for respiratory disease treatment.
Ultra-low coverage fragmentomic model of cell-free DNA for cancer detection based on whole-exome regions
Authors: Sangphukieo Apiwat , Noisagul Pitiporn , Thongkumkoon Patcharawadee , Chaiyawat Parunya 
Published: February 2024

AbstractCell-free DNA (cfDNA) has shown promise as a non-invasive biomarker for cancer screening and monitoring. The current advanced machine learning (ML) model, known as DNA evaluation of fragments for early interception (DELFI), utilizes the short and long fragmentation pattern of cfDNA and has demonstrated exceptional performance. However, the application of cfDNA-based model can be limited by the high cost of whole-genome sequencing (WGS). In this study, we present a novel ML model for cancer detection that utilizes cfDNA profiles generated from all protein-coding genes in the genome (exome) with only 0.08X of WGS coverage. Our model was trained on a dataset of 721 cfDNA profiles, comprising 426 cancer patients and 295 healthy individuals. Performance evaluation using a ten-fold cross-validation approach demonstrated that the new ML model using whole-exome regions, called xDELFI, can achieve high accuracy in cancer detection (Area under the ROC curve; AUC=0.896, 95%CI = 0.878 - 0.916), comparable to the model using WGS (AUC=0.920, 95%CI = 0.901 – 0.936). Notably, we observed distinct fragmentation patterns between exonic regions and the whole-genome, suggesting unique genomic features within exonic regions. Furthermore, we demonstrate the potential benefits of combining mutation detection in cfDNA with xDELFI, which enhance the model sensitivity. Our proof-of-principle study indicates that the fragmentomic ML model based solely on whole-exome regions retains its predictive capability. With the ultra-low sequencing coverage of the new model, it could potentially improve the accessibility of cfDNA-based cancer diagnosis and aid in early detection and treatment of cancer.
Resilience, mental health, sleep, and smoking mediate pathways between lifetime stressors and Multiple Sclerosis severity
Authors: Polick Carri S. , Darwish Hala , de Olivera Leo Pestillo , Watson Ali , Nickenig Vissoci Joao Ricardo , Calhoun Patrick S. , Ploutz-Snyder Robert , Connell Cathleen M. , Braley Tiffany J. , Stoddard Sarah A. 
Published: February 2024

AbstractIntroLifetime stressors (e.g., poverty, violence, discrimination) have been linked to Multiple Sclerosis (MS) features; yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated.AimTo deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience.MethodsAdults with MS (N=924) participated in an online survey through the National MS Society listserv. Structural Equation Modeling was used to examine the direct and indirect effect of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity and interference), via resilience, mental health (anxiety and depression), sleep disturbance, and smoking.ResultsThe final analytic model had excellent fit (GFI=0.998). Lifetime stressors had a direct relationship with MS severity (β=0.27, p<.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of mediation was significant (β=0.45).ConclusionsThis work provides foundational evidence to inform conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve disease course.HighlightsLifetime stressors directly and indirectly relate to MS severity.Resilience, mental health, sleep, and smoking were mediators.Resilience attenuated the effects of stressors on mental health, sleep, and smoking.Multi-modal interventions are needed to help improve MS symptom severity.
Associations of a multidimensional polygenic sleep health score and a sleep lifestyle index on health outcomes and their interaction in a clinical biobank
Authors: Paz Valentina , Wilcox Hannah , Goodman Matthew , Wang Heming , Garfield Victoria , Saxena Richa , Dashti Hassan S. 
Published: February 2024

AbstractSleep is a complex behavior regulated by genetic and environmental factors, and is known to influence health outcomes. However, the effect of multidimensional sleep encompassing several sleep dimensions on diseases has yet to be fully elucidated. Using the Mass General Brigham Biobank, we aimed to examine the association of multidimensional sleep with health outcomes and investigate whether sleep behaviors modulate genetic predisposition to unfavorable sleep on mental health outcomes. First, we generated a Polygenic Sleep Health Score using previously identified single nucleotide polymorphisms for sleep health and constructed a Sleep Lifestyle Index using data from self-reported sleep questions and electronic health records; second, we performed phenome-wide association analyses between these indexes and clinical phenotypes; and third, we analyzed the interaction between the indexes on prevalent mental health outcomes. Fifteen thousand eight hundred and eighty-four participants were included in the analysis (mean age 54.4; 58.6% female). The Polygenic Sleep Health Score was associated with the Sleep Lifestyle Index (β=0.050, 95%CI=0.032, 0.068) and with 114 disease outcomes spanning 12 disease groups, including obesity, sleep, and substance use disease outcomes (p<3.3×10−5). The Sleep Lifestyle Index was associated with 458 disease outcomes spanning 17 groups, including sleep, mood, and anxiety disease outcomes (p<5.1×10−5). No interactions were found between the indexes on prevalent mental health outcomes. These findings suggest that favorable sleep behaviors and genetic predisposition to healthy sleep may independently be protective of disease outcomes. This work provides novel insights into the role of multidimensional sleep on population health and highlights the need to develop prevention strategies focused on healthy sleep habits.
Trends in Gaps of Care for Congenital Heart Disease Patients: Implications for Social Determinants of Health and Child Opportunity Index
Authors: Zaidi Abbas H. , Alberts Adam , Chowdhury Devyani , Beaty Claude , Brewer Benjamin , Chen Ming Hui , de Ferranti Sarah D. 
Published: February 2024

AbstractBackgroundLifelong continuity of care is imperative for patients with congenital heart disease (CHD); unfortunately, gaps in care (GIC) are common.MethodsAll patients aged 0-34 years followed at a pediatric subspecialty hospital (primary location Delaware; satellites covering Pennsylvania, New Jersey, Maryland) with CHD who underwent surgery between January 2003 and May 2020 were included. Patients were categorized as simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health factors such as age, race, ethnicity, sex, language, insurance status, and Child Opportunity Index based on home address zip code were analyzed.ResultsOf 2012 CHD patients, a GIC of ≥3 years was identified in 56% (n=1119). The proportion of patients with GIC per year increased for all patients. Multivariable longitudinal models with all CHD patients showed that GIC are increasing for patients who are ≥10.5 years old, have simple CHD, live out of state, live farther from a site of care (hospital or satellite clinics), receive public insurance and/or have less protection with additional insurance plans, and reside in low Child Opportunity Index neighborhoods. A separate model for only moderate/complex CHD patients showed similar findings. Neither longitudinal model showed race/ethnicity as significant for increasing GIC trends.ConclusionsGIC have continued to increase with an aging CHD population with social determinants of health factors specifically related to insurance, access, and neighborhood opportunity. Attenuating GIC necessitates standardized practices while simultaneously addressing the impact of SDOH on all CHD patients.Clinical PerspectiveWhat is new?This study is the first to examine gaps in care (GIC) trends over time in patients with repaired congenital heart disease (CHD) and found that almost half had GIC.Over 2 decades, GIC are increasing for certain subpopulations of CHD patients based on social determinants of health, including being older, lacking insurance, and residing in low Child Opportunity Index neighborhoods.What Are the Clinical Implications?GIC are worsening in certain subpopulations of CHD patients, including those with low Child Opportunity Index, lack of insurance, or poor access to health care systems.CHD programs must target social determinants of health factors to improve ongoing care and long-term outcomes for all patients.
Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases
Authors: Nakajima Masahiro , Tanaka Nobukiyo , Motouchi Sei , Kobayashi Kaito , Shimizu Hisaka , Abe Koichi , Hosoyamada Naoya , Abara Naoya , Morimoto Naoko , Hiramoto Narumi , Nakata Ryosuke , Takashima Akira , Hosoki Marie , Suzuki Soichiro , Shikano Kako , Fujimaru Takahiro , Imagawa Shiho , Kawadai Yukiya , Wang Ziyu , Kitano Yoshinao , Nihira Takanori , Nakai Hiroyuki , Taguchi Hayao 
Published: February 2024

Abstractβ-1,2-Glucans are natural glucose polymers that play important physiological roles, including as symbiotic or pathogenic factors and in osmoregulation. Phylogenetically new glycoside hydrolase (GH) families have recently been identified from β-1,2-glucanase (SGL) sequences from bacteria (GH144) and a fungus (GH162). In this study, we identified four phylogenetically new groups (Groups 1–4), and determined that these families, together with GH144, GH162, and GH189, a family of transglycosylase domains in cyclic β-1,2-glucan synthases, form a superfamily. Biochemical analysis of six proteins in these groups revealed that the proteins in Groups 1–3 showed hydrolytic activity specific to β-1,2-glucan. The kinetic parameters of the enzymes of Groups 1–3 were similar to GH144 and GH162 SGLs, indicating that these enzymes were SGLs. Optical rotation analysis revealed that the SGLs followed an anomer-inverting mechanism. Structural analysis and prediction of the proteins in Groups 1–4, GH144, GH162, and GH189 suggested that Groups 1–3 and GH144 had the same reaction mechanism. Nevertheless, Groups 1–3 were dispersed irregularly in the superfamily. Overall, we determined that Groups 1–3 were new GH families, GHxxx, GHyyy, and GHzzz, respectively, and proposed that this superfamily be called an SGL superfamily because of the phylogenetical, functional, and structural relationships within the superfamily.HighlightsWide variety of glycoside hydrolases is far beyond our understanding.Functional and structural analysis identified three new glycoside hydrolase families.Molecular evolution with irregular changes in reaction mechanism was revealed.
Optogenetic control of pheromone gradients reveals functional limits of mating behavior in budding yeast
Authors: Banderas Alvaro , Hofmann Maud , Cordier Celine , Le Bec Matthias , Elizondo Carolina , Chiron Lionel , Pouzet Sylvain , Scolari Vittore , Hersen Pascal 
Published: February 2024

AbstractCell-cell communication through diffusible signals allows distant cells to coordinate biological functions. Such coordination depends on the signal landscapes generated by emitter cells and the sensory capacities of receiver cells. In contrast to morphogen gradients in embryonic development, microbial signal landscapes occur in open space with variable cell densities, spatial distributions, and physical environments. How do microbes shape signal landscapes to communicate robustly under such circumstances remains an unanswered question. Here we combined quantitative spatial optogenetics with biophysical theory to show that in the mating system of budding yeast— where two mates communicate to fuse—signal landscapes convey demographic or positional information depending on the spatial organization of mating populations. This happens becauseα-factor pheromone and its mate-produced protease Bar1 have characteristic wide and narrow diffusion profiles, respectively. Functionally, MATαpopulations signal their presence as collectives, but not their position as individuals, and Bar1 is a sink of alpha-factor, capable of both density-dependent global attenuation and local gradient amplification. We anticipate that optogenetic control of signal landscapes will be instrumental to quantitatively understand the spatial behavior of natural and engineered cell-cell communication systems.
Polyketide synthase-derived sphingolipids determine microbiota-mediated protection against pathogens inC. elegans
Authors: Peters Lena , Drechsler Moritz , Pees Barbara , Angelidou Georgia , Salzer Liesa , Moors Karlis Arturs , Paczia Nicole , Schulenburg Hinrich , Shi Yi-Ming , Kaleta Christoph , Witting Michael , Bode Helge B. , Dierking Katja 
Published: February 2024

AbstractProtection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematodeCaenorhabditis elegansand its microbiota isolatePseudomonas fluorescensMYb115 that is known to protect againstBacillus thuringiensis(Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affectC. eleganstolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.
A rapid, cost-effective, colorimetric LAMP assay (CLASS) for detecting invasive malaria vector,Anopheles stephensi
Authors: Rafferty Cristina , Raise Gloria , Scaife Jenyiah , Abongo Bernard , Omondi Seline , Milanoi Sylvia , Muchoki Margaret , Onyango Brenda , Ochomo Eric , Zohdy Sarah 
Published: February 2024

AbstractAnopheles stephensi, an invasive malaria vector in Africa, has the potential to impact the landscape of malaria on the continent, threatening to put an additional 126 million people per year at risk of malaria, largely in peri-urban/urban areas. To accelerate the early detection and rapid response toAn. stephensiand ensure no gains made in malaria control and elimination are lost, it is critical to confirm the presence of the species and the geographic extent of its spread to inform control. However, morphological identification may be misinterpreted if specimens are damaged and existing molecular species confirmation assays require specialized laboratory equipment and training and may be challenging to interpret, requiring additional sequencing confirmation. A colorimetric rapid loop-mediated isothermal amplification (LAMP) assay for molecularAn. stephensispecies identification was developed and optimized. The colorimetric assay requires only a heat source and reagents and can be used with or without DNA extraction resulting in positive color change in 30-35 minutes. To determine analytical sensitivity, a 1:10 dilution series of the DNA extract was conducted showing 100% assay sensitivity down to 0.003 nanograms. To determine specificity, three differentAn. stephensilaboratory strains (STE2, SDA 500, UCI), 8 other Anopheles mosquito species, andAedes aegyptiwere compared, and the results indicated 100% specificity across these species. To determine use without the need for DNA extraction, samples evaluated included a single mosquito leg, whole adult or larval mosquitoes, and pooled DNA extract from several mosquito species. A total of 1687 individual reactions were tested during optimization and all LAMP assay results were compared against the conventional PCR assay and confirmed through Sanger sequencing. To validate the optimized assay on wild caught specimens, DNA extracted from 12 wild caught, sequence-confirmedAn. stephensifrom Marsabit, Kenya, were tested and the colorimetric assay was accurate in identifying all of the specimens asAn. stephensi. The assay described presents an opportunity to accelerateAn. stephensimolecular identification in new and existing locations in Africa, within its endemic range, and globally. These findings present a simple, rapid, unique alternative to existing PCR and sequencing-basedAn. stephensispecies identification and confirmation strategies. With additional field validation studies, molecular screening tools like the colorimetric LAMP-based An.stephensispecies identification (CLASS) assay fill an important gap of rapid confirmation of this invasive vector and presents an ideal opportunity to better understand the spread of the species in Africa and other recently invaded areas, thus accelerating a response to mitigate its long-term impacts on malaria on the continent.
Accumulation dynamics of defective genomes during experimental evolution of two betacoronaviruses
Authors: Hillung Julia , Olmo-Uceda María J. , Muñoz-Sánchez Juan C. , Elena Santiago F. 
Published: February 2024

AbstractVirus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When coinfected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can disrupt infectious virus replication, impact immune responses, and affect viral persistence or evolution. Understanding the dynamics of DVGs alongside standard viral genomes during infection remains unclear. To address this, we conducted a long-term experimental evolution of two betacoronaviruses, the human coronavirus OC43 (HCoV-OC43) and the murine hepatitis virus (MHV), in cell culture at both high and low multiplicities of infection (MOI). We then performed RNA-seq at regular time intervals, reconstructed DVGs, and analyzed their accumulation dynamics. Our findings indicate that DVGs evolved to exhibit greater diversity and abundance, with deletions and insertions being the most common types. Notably, some high MOI deletions showed very limited temporary existence, while others became prevalent over time. We observed differences in DVG abundance between high and low MOI conditions in HCoV-OC43 samples. The size distribution of HCoV-OC43 genomes with deletions differed between high and low MOI passages. In low MOI lineages, short and long DVGs were most common, with an additional cluster in high MOI lineages which became more prevalent along evolutionary time. MHV also showed variations in DVG size distribution at different MOI conditions, though less pronounced compared to HCoV-OC43, suggesting a more random distribution of DVG sizes. We identified hotspot regions for deletions that evolved at high MOI, primarily within cistrons encoding structural and accessory proteins. In conclusion, our study illustrates the widespread formation of DVGs during betacoronavirus evolution, influenced by MOI and cell- and virus-specific factors.
Motor adaptation to environment changes predicting object behaviour can be flexible and implicit
Authors: Modchalingam Shanaathanan , King Andrew , ’t Hart Bernard Marius , Henriques Denise Y. P. 
Published: February 2024

AbstractHuman motor behaviour can adapt in response to perturbations in the environment, either through updating existing motor control models or by creating context-specific motor memories or strategies. Context informed motor adaptation can allow for flexible motor behaviour in changing environments, albeit with costs associated with action selection. While our dynamic natural environments necessitates flexible motor behaviour, many studies of motor control and motor learning limit their focus to model-based motor adaptation. In this study, we investigate if motor adaptation is flexible when a perturbation is applied to either the acceleration of a rolling ball, or to the throw direction at release during a virtual throw-to-target task. We also determine if the tendency for model updating is influenced by immersive and informative visual cues indicating the presence of a perturbation, such as the slant of a surface on which thrown objects travel. Despite the visual slant allowing for more rapid performance change when adapting to both perturbation scenarios, our findings reveal that perturbations resembling accelerations enabled flexible motor adaptation regardless of the presence of the slant cue. Perturbations in the throw direction conversely predominantly led to internal model updating. Additionally, informative visual slant properties of the task surface elicited implicit, slant-specific changes in performance. Our findings underscore the role of visual properties of both perturbations and environments in flexible motor learning.