bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid Signature of Motile Human Sperm: Characterization of Sphingomyelin, Ceramide and Phospholipids with a Focus on Very Long Polyunsaturated Fatty Acid
Authors: Oresti Gerardo M. , Luquez Jessica M. , Belmonte Silvia A. 
Published: February 2025

AbstractSperm membrane lipids play a crucial role in male fertility, influencing sperm motility, viability, and functional competence. This study provides a comprehensive characterization of the phospholipid and sphingolipid composition in highly motile human spermatozoa obtained through the swim-up method, a widely used technique in assisted reproductive technology (ART). Using two-dimensional thin-layer chromatography and phosphorus analysis, we identified choline glycerophospholipids (CGP, 45%), ethanolamine glycerophospholipids (EGP, 26%), and sphingomyelin (SM, 17%) as predominant phospholipids, with minor components including cardiolipin, lysophospholipids, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and neutral lipids. Gas chromatography analysis of glycerophospholipids (GPL) revealed a high long chain (C20-C22) polyunsaturated fatty acid (PUFA) content (46.3%), particularly docosahexaenoic acid (DHA, 22:6n-3), which was more abundant in CGP (46%) than EGP (26%). Sphingolipid analysis indicated that ceramide (Cer) and SM shared similar fatty acid profiles due to their metabolic relationship, with very long-chain (VLC) PUFA (≥C26) being more prevalent in SM (10%) than in Cer (6%). Additionally, argentation chromatography allowed the identification of highly unsaturated VLCPUFA species in Cer, including 28:3n-6, 28:4n-6, and 30:4n-6, which had not been previously quantified in motile human spermatozoa. Given the essential function of sphingolipid metabolism in spermatogenesis, capacitation, and acrosomal exocytosis, our findings suggest that the balance of VLCPUFA-containing SM and Cer emerges as a key factor in sperm performance and fertilization potential. This study provides novel insights into the lipid signature of human sperm and highlights the relevance of membrane lipid remodeling for male fertility and ART outcomes.
Reactive Pericytes Lead to Microvascular Dysfunction and Cortical Neurodegeneration During Experimental Autoimmune Encephalomyelitis
Authors: Yousefi Mohammadreza , Özkan Ayşe , Özmen Kaan Kutay , Uysallı Yiğit , Mamipour Mina , Akkaya Nazan , Amandi Amir-Reza Dalal , Atbaşi Abdulsamet , Heidarzadeh Morteza , Erdener Şefik Evren , Kawakami Naoto , Kiraz Alper , Özdemir Yasemin Gürsoy , Vural Atay 
Published: February 2025

AbstractThe mechanisms underlying neurodegeneration in multiple sclerosis remain incompletely understood. In this study, we aimed to investigate the role of vascular dysfunction in cortical neurodegeneration using a chronic cranial window model of experimental autoimmune encephalomyelitis in mice. After the induction of experimental autoimmune encephalomyelitis with myelin oligodendrocyte glycoprotein peptides in C57BL/6J mice, we assessed cerebrovascular reactivity though a chronic cranial window using laser speckle contrast imaging and intrinsic optical signal imaging in awake animals. We observed a significant reduction in cortical cerebrovascular reactivity during peak inflammation in the EAE group, as detected by laser speckle contrast imaging after 5% hypercapnia (p=0.04) and optical signal imaging after whisker stimulation (p=0.008). Histological analysis revealed a diffuse increase in CD13+ pericyte coverage (p=0.001), accompanied by focal IgG deposition within the microvascular lumen (p=0.04) and increased amount of CD45+ leukocytes stalled in microvessels (p=0.03) in the cortex of experimental autoimmune encephalomyelitis mice. Microglial activation was also present in the cortex of experimental autoimmune encephalomyelitis mice (p=0.04) and was particularly evident around microvessels with IgG deposition. Subpial and intracortical foci exhibiting loss of NeuN reactivity (p=0.03) and axonal loss (p=0.007) were detected in experimental autoimmune encephalomyelitis, but not in control mice. Altogether, these results demonstrate that microvascular function and neurovascular unit elements are globally affected in the cortex during autoimmune neuroinflammation and is related to neurodegeneration.
Genome-wide cline analysis identifies new locus contributing to a barrier to gene flow across anAntirrhinumhybrid zone
Authors: Field David L , Stankowski Sean , Reiter Taylor , Polechova Jitka , Bradley Desmond , Richardson Daniel , Pal Arka , Shipilina Daria , Boell Louis , Pickup Melinda , Xue Yongbiao , Coen Enrico , Barton Nicholas 
Published: February 2025

AbstractIdentification of the genomic regions that contribute to reproductive isolation and how they interact is a major goal of evolutionary genetics. Much effort has focused on locating candidate genes and potential barrier loci by scanning genomes for regions of excess differentiation (FST). An alternative, and perhaps more robust approach, would be to scan for genomic regions exhibiting steep clines in allele frequency across a hybrid zone. Here we develop this approach and apply it to genomic data from across a hybrid zone between varieties ofAntirrhinum majussubspeciesmajuswith different flower colour patterns (A. m. mvar.pseudomajusandA. m. mvar.striatum). Most steep clines are clustered in seven genomic regions, only four of which were present fromFSTscans between all pair-wise comparisons. Six of these regions carry previously identified loci that influence flower colour in the hybrid zone. The seventh region harbours a novel locus, RUBIA, modifying magenta intensity. Clines atRUBIAapproached towards fixation on magenta side of the hybrid zone, whilst remaining polymorphic on the yellow side. This polymorphism on the yellow side may reflect a smaller phenotypic effect ofRUBIAin yellow compared to magenta genetic backgrounds. Our findings illustrate how whole-genome cline scans in hybrid zones can robustly detect genomic regions contributing to phenotypic differences and highlight how different reproductive barrier loci interact across the genome.
Boosting reliability when inferring interactions from time series data in gene regulatory networks
Authors: Greco Mattia , Tersenghi Federico Ricci , Martin Olivier C. 
Published: February 2025

AbstractIn the context of the dynGENIE3 [13] approach for inferring regulatory network interactions from time-series data, we show that it is possible to modify that algorithm to significantly enhance its prediction reliability. To quantify the level of reliability, we used ground-zero truths based on simulated datasets generated by the GeneNetWeaver [22] tool. Our work introduces novel methods leveraging time-lagged correlations and estimators of mRNA decay rates, leading to significantly improved driver-target inference. Additionally, a temperature-based rescaling of priors was developed to further enhance prediction reliability. Results demonstrate substantial improvements in performance with a particularly notable increase in AUPRC scores. These advances underscore the possible gains resulting from incorporating priors into gene regulatory network inference.
A temporary challenge by tumor cells can lead to a permanent partial-impairment of memory CD8 T cell function
Authors: Laubreton Daphné , Prieux Margaux , Djebali Sophia , Dubois Maxence , De Bernard Simon , Gandrillon Olivier , Arpin Christophe , Marvel Jacqueline 
Published: February 2025

AbstractMemory CD8 T cells typically exhibit improved effector functions compared to their naive counterparts. However, under certain activation conditions, such as chronic viral infections or cancer, these cells may develop functional defects. In this study, we compared the functional quality of memory CD8 T cells generated following tumor rejection with those arising from an acute viral infection. We found that tumor-induced (Tum-CD8) memory cells exhibited a distinct phenotype and transcriptomic profile compared with viral-induced (Vir-CD8) memory cells. These memory cells are characterized by the expression of inhibitory receptors and displayed altered functions including reduced IFNγ and TNFα production as well as changes in integrin expression. Additionally, the protective capacity of Tum-CD8 memory cells was flawed relative to that of Vir-CD8 memory cells. Importantly, the functional defects of Tum-CD8 persisted upon viral recall. Together, these findings indicate that transient tumoral stimulation can imprint a stable partial exhaustion-like program on memory CD8 T cells.
Metabolically purified human stem cell-derived hepatocytes reveal distinct effects of Ebola and Lassa viruses
Authors: Prescott Joseph B. , Liu Kevin J. , Lander Angelika , Pek Nicole Min Qian , Jha Sawan Kumar , Bokelmann Marcel , Begur Manali , Koh Pang Wei , Yang Henry , Lim Bing , Red-Horse Kristy , Weissman Irving L. , Loh Kyle M. , Ang Lay Teng 
Published: February 2025

SUMMARYEbola and Lassa viruses require biosafety-level-4 (BSL4) containment, infect the liver, and cause deadly hemorrhagic fevers. The cellular effects of these viruses, and whether different families of hemorrhagic-fever viruses elicit similar effects, remain fundamental questions in BSL4 virology. Here, we introduce a new metabolic selection approach to create nearly-pure hepatocytes from human pluripotent stem cells, killing non-liver cells by withholding essential nutrients. Unexpectedly, Ebola and Lassa exerted starkly different effects on human hepatocytes. Ebola infection activated the integrated stress response (ISR) and WNT pathways in hepatocytes in vitro and killed them, whereas Lassa did not. Within non-human primates, Ebola likewise infected hepatocytes and activated ISR signalingin vivo. In summary, we present a single-cell transcriptional and chromatin accessibility roadmap of human hepatocyte differentiation, purification, and viral infection.
Development of an Australian Clinical Practice Guideline on methylenedioxymethamphetamine (MDMA)-assisted Psychotherapy for Post-traumatic Stress Disorder
Authors: Jing Yong Alene Sze , Brennan Sue E , Bratuskins Suzie , Freeburn Aimée , Bedi Gillinder , Burke Rimona , Haines Terry , Hollick Mary , Jones Kimberley Ann , Lawrence Andrew J , Lee Yong Yi , McFarlane Alexander C , Parker Stephen , Procter Nicholas , Spicer Liam , Somogyi Andrew A. , Stafrace Simon , Watts Stacey , Walton Clare , Wilson Kay , Bell J Simon 
Published: February 2025

AbstractIntroductionDespite recent clinical and research interest, medical use of psychedelics has not been legalised in most jurisdictions. The Australian Therapeutic Goods Administration rescheduled methylenedioxymethamphetamine (MDMA) in July 2023 to permit authorised prescribing of MDMA for Post-traumatic Stress Disorder (PTSD) outside of the clinical trial setting.ObjectiveThis manuscript describes the development of the Australian Clinical Practice Guideline on MDMA-assisted psychotherapy (MDMA-AP) for PTSD.MethodsThe Guideline will be developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) process. The Guideline will consider the benefits and harms of MDMA-AP compared to other treatments in people with PTSD. High quality systematic reviews identified via an overview of systematic reviews will be used as index and supplementary reviews. Using the GRADE Evidence-to-Decision framework, the multidisciplinary Guideline Development Group (GDG) will consider treatment benefits and harms, certainty of evidence, patient preferences and values, resources, equity, acceptability and feasibility. The GDG will be supported by a Stakeholder Group, Expert Group, Conflict of Interest Oversight Committee, and Evidence Review Team. The Guideline will be developed using an integrated knowledge translation approach, emphasising the co-production of knowledge through active participation and shared decision-making with end-users.ConclusionThe Guideline will be published on the digital platform MAGICapp and disseminated in peer-reviewed publications, professional conferences and via specific stakeholder groups. A Companion Guide will be developed for people living with PTSD and their carers, family members, and supports.
STILLBIRTHS: PREVALENCE, RISKS AND CLINICAL INTERVENTIONS IMPACT AMONG WOMEN IN KWAHU GOVERNMENT HOSPITAL
Authors: Abdul-Salaam Gaddafi , Owusu-Adjei Michael , Ansong Kwakye , Opong Joseph Manasseh , Osei Nana , Seth Ampadu 
Published: February 2025

AbstractBackgroundIt is the expectation and joy of every expectant mother and her immediate family to welcome into their fold healthy newborn babies after each gestational period. Unfortunately, in most instances this expectation is marred by complications which ocassionally result in the death of the unborn/newborn child known as stillbirth. This anti-climax leads to unexpected periods of sadness for both mother and her immediate family members. The growing incidence of stillbirths is acknowledged worldwide and said to be associated with many factors both maternal and child health conditions. However, the key question is how many of these maternal and child conditions could have been anticipated and prevented. Addressing this challenge will require a review of specific instutional policy frameworks that deals with the incidence of stillbirths on a case by case basis. In this retrospective study, record of stillbirths over a 5-year period is examined to determine impact of clinical interventions on prevalence and risks among women within Kwahu West municipality in Ghana.MethodA retrospective cross-sectional study to examine recorded cases of stillbirths over a 5-year period among women in Kwahu South Hospital to determine clinical intervention impact on prevalence, risks and control was undertaken. Using established clinical audit recommendations, this study examines the effectiveness of recommendations and its impact. Socio-demographic features such as age, educational level, gestational maturity, medical conditions of mother and child, delivery method, recorded stillbirth types, fetal sex and patient’s geographical location. All statistical analysis was performed using R programming tool.ResultsClinical interventions and its impact show a reduction in stillbirth types from 4 to 2 from 2019-2023. However, macerated and fresh stillbirths remain the most dominant stillbirth types recorded with and without medical conditions in urban communities. Sustained decreases in the number of stillbirths across all years including the elimination of early neonatal deaths and intra-uterine fetal deaths from 2021-2023 is observed.ConclusionEstablished institutional clinical audit on each stillbirth occurrence provided in-depth analysis on case-by-case basis. This practice led to the use of clinically designed interventions resulting from audit reviews on specific cases to help address similar situations. Even though a reduction in the number of recorded stillbirths from 20.83 per 1000 live births in 2019 to 10.81 per 1000 live births in 2023 is noted, a staggering 76.88% share of stillbirths among patients and fetus with no medical condition presents a serious challenge to healthcare providers. Detailed review of all cases that excludes nothing irrespective of clinical presentation can provide important insight into the incidence of high stillbirth rates among women with such presentation.
A technology-based randomized controlled trial of self-affirmation and gain-framed health messaging to reduce sedentary behavior in older adults
Authors: Ai Meishan , Thovinakere Nagashree , Walker Caitlin S. , Ordway Cora , Quinoñez Elizabeth , Melsky Emily , D’Agostino Frank , Tobias Calvin , Whitfield-Gabrieli Susan , Phillips Siobhan M. , Pindus Dominika M. , Hilman Charles , Morris Timothy P. , Kramer Arthur F. , Geddes Maiya R. 
Published: February 2025

AbstractObjectiveSedentary behavior significantly increases the risk for chronic diseases and cognitive decline in aging, underscoring the need for effective interventions. Older adults exhibit a ‘positivity effect’, whereby processing of positive information is prioritized over negative information. In addition, self-affirmation was shown to reduce sedentary behavior in younger adults, but its effects in older adults remain unknown. This study tested a novel, technology-based intervention combining daily self-affirmation and gain-framed health messages to reduce sedentary behavior in older adults.MethodsIn a 6-week randomized controlled trial (NCT0431536), 48 cognitively unimpaired, sedentary older adults were randomized into two groups: The intervention group (mean age=70.0±5.4years) completed daily self-affirmation based on their highest-ranked value, followed by gain-framed health messages. The active control group (mean age=68.4±5.0years) performed self-affirmation on their lowest-ranked value, followed by loss-framed messages. This was a single-blinded clinical trial that incorporated a hybrid efficacy and implementation design. Thus, information about intervention feasibility was examined. In addition, baseline motivational traits, including reward sensitivity, were assessed as moderators of behavior change. The neural basis of self-affirmation and gain-framed health messaging was examined at baseline using a task-based, event-related fMRI paradigm across groups, after randomization at the outset of the intervention.ResultsThe intervention showed high adherence (0.92±0.08) and positive ease-of-use ratings. While the intervention did not significantly reduce sedentary behavior compared to the active control condition, increased reward sensitivity predicted reduced sedentary behavior across all participants. FMRI results showed increased ventral striatal activation in the intervention group, compared to the active control group during reading of gain-framed compared to neutral messages.ConclusionsThis study supports the feasibility of technology-based sedentary beahvior reduction interventions for older adults. While self-affirmation combined with gain-framed messaging did not significantly reduce sedentary behavior, gain-framed messages engaged the reward network, and reward sensitivity predicted future reduction in sedentary behavior.
Harnessing Greater Statistical Power: Comprehensive Evaluation of Disease Modifying Treatment Effects Across All or Multiple Post-Baseline Visits Compared to the Last Visit for Alzheimer’s Disease Clinical Trials
Authors: Wang Guoqiao , Chen Tianle , O’Gorman John , Li Yan , Li Caiyan , Guizzetti Leonard , Mangal Brian , Wang Whedy , Wu Shuang , Inman Dave , McDade Eric , Bateman Randall J. 
Published: February 2025

AbstractBackgroundIn Alzheimer’s disease (AD) clinical trials, efficacy inference is traditionally based on the last visit (e.g., 18 months). However, recent studies suggest that disease-modifying treatment effects may emerge as early as 3 months post-baseline.ObjectiveTo explore this further, our study aimed to assess the increased statistical power achieved by incorporating all or multiple post-baseline visits to estimate treatment effect, compared to relying solely on the last visit.MethodsWe developed explicit formulas for the base functions of the natural cubic spline model, ensuring compatibility with standard SAS procedures. Through simulations using disease progression trajectories from ClarityAD and TRAILBLAZER-ALZ2 trials, we comprehensively evaluated various models in terms of power and type I error. Additionally, we offer SAS codes that to facilitate seamless implementation of different modeling approaches.ResultsSimulations based on ClarityAD and TRAILBLAZER-ALZ2 disease trajectories demonstrated that models incorporating multiple or all post-baseline visits yield greater power than those using only the last visit, while maintaining Type I error control. Furthermore, when three post-baseline visits were included, adding more visits resulted in minimal power gains.ConclusionsOur findings support prioritizing statistical models that incorporate multiple or all post-baseline visits for treatment efficacy inference, as they offer greater efficiency than models relying solely on the last visit.
Potential and Limitations of the MinION Nanopore array for miRNA-Enabled Early Cancer Detection
Authors: Kanavarioti Anastassia , Rafiq Aleena 
Published: February 2025

SummaryThe 2024 Nobel Prize in Physiology or Medicine was awarded to the pioneers who reported that microRNAs (miRNAs) regulate and direct the switch between physiological and pathological pathways via their over- or under-expression. The discovery has not yielded any health benefit primarily due to raw data with no clear distinction between healthy and diseased blood samples. MiRNAs exist at femtomolar level in biological fluids, and typically quantified using amplification-based techniques. Experimental nanopores have illustrated potential for trace analysis including amplification-free miRNA quantification. We repurposed the MinION, the only commercially available nanopore-array device, and developed unique probes and protocols to quantify microRNAs in blood and urine. Our 2024 report revealed (i) miRNA copies are proportional to the total RNA isolated from the biospecimen, and (ii) several known miRNA cancer biomarkers were 1.8-fold overexpressed in blood samples from breast, prostate and pancreatic cancer patients compared to healthy. In contrast to literature reports sample variability was undetectable after normalization to the same RNA content. Here the earlier data were confirmed, and the conclusions extended to ovarian, lung, and colorectal cancer. The potential of the ready-to-use MinION/Yenos platform for multiple cancer early detection (MCED) using blood or urine is discussed.
Immunological and clinical markers of post-acute sequelae of COVID-19: Insights from mild and severe cases six months post-infection
Authors: Mouton William , Djebali Sophia , Villard Marine , Allatif Omran , Chauvel Cécile , Benezech Sarah , Vanhems Philippe , Marvel Jacqueline , Walzer Thierry , Trouillet-Assant Sophie 
Published: February 2025

SUMMARYPost-acute sequelae of COVID-19 (PASC) is a complex and multifaceted clinical challenge requiring to emphasize its underlying pathophysiological mechanisms.This study assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two patient cohorts who experienced mild (n=270) or severe (n=188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57.4% of patients, respectively, developed PASC.Blood analysis showed that mains differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC.However, patients with PASC displayed altered CD4+and CD8+memory T-cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA+effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy.HighlightsNine months post-initial SARS-CoV-2 infection, over 40% of patients developed PASCRegardless of PASC, the initial disease form influenced the main immune differencesPASC led to altered memory T-cell subsets with elevated TEMRA phenotypePASC presence is associated with disease form, initial symptom count and duration