bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage
Authors: Efthymiou Georgios , Compare Coralie , Lohmann Eugénie , Kousteridou Paraskevi , Bertrand Pierre , Carr Heather S. , Ben-Sahra Issam , Nemazanyy Ivan , Tubiana Sarah Simha , Hussain Zainab , Finetti Pascal , Bertucci François , Bidaut Ghislain , Lachaud Christophe , Guillaumond Fabienne , Tomasini Richard , Vasseur Sophie 
Published: January 2025

AbstractThe excessive production of extracellular matrix (ECM) and the metabolic adaptations in pancreatic ductal adenocarcinoma (PDAC) contribute individually to enhanced chemoresistance, dramatic tumor progression and dismal patient survival. However, ECM-driven metabolic alterations that promote chemoresistance in PDAC are so far unexplored. Here, we usein-vitro-generated ECM bio-scaffolds that recapitulate cell-ECM interactions and induce broad metabolic alterations in PDAC cells. High-throughput integration of multi-omics datasets coupled with metabolic tracing showed that the ECM enhances the generation of guanylates in PDAC cells, the accumulation of which alleviates oxaliplatin-induced DNA damage, and boosts PDAC cell proliferation. These events are guided by the guanosine monophosphate (GMP)-producing enzymes Impdh and Gmps, the expression of which correlated with that of matrisomal and DNA repair genes in PDAC patient samples. We propose that targeting ECM-driven metabolic processes, like the enhanced Impdh activity, may be an effective therapeutic approach for PDAC patients that bypasses the negative side effects of direct targeting of the ECM itself.
Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds
Authors: Meunier Dominique , Corona-Torres Ricardo , Boulton Kay , Wu Zhiguang , Ballantyne Maeve , Glendinning Laura , Ahmad Anum Ali , Borowska Dominika , Taylor Lorna , Vervelde Lonneke , del Pozo Jorge , Vasilogianni Marili , Jaramillo-Ortiz José , Sanchez-Arsuaga Gonzalo , Psifidi Androniki , Tomley Fiona , Watson Kellie A. , McGrew Michael J. , Stevens Mark P. , Blake Damer P. , Hume David A. 
Published: January 2025

AbstractEffective mucosal immunity in the intestine involves a fine balance between tolerance of the microbiome, recognition and elimination of pathogens, and inflammatory tissue injury. The anti-inflammatory cytokine IL10 regulates these processes in the intestines of mice and humans; the anti-inflammatory activity of IL10 is also conserved in birds. To determine the function of IL10 in avian mucosal immunity, we generated germ line modifications of the chickenIL10locus to abolish or reduce IL10 expression.In vitroanalysis of macrophage response to lipopolysaccharide confirmed the loss of IL10 protein expression, the lack of dosage compensation in heterozygotes, and prevention of autocrine inhibition of nitric oxide production in homozygous IL10 knockout macrophages. IL10-deficiency significantly altered the composition of the caecal microbiome, but unlike IL10-deficient mice and humans, IL10-deficient chickens did not exhibit spontaneous colitis. Following experimental challenge withSalmonella entericaserovar Typhimurium orCampylobacter jejuniin IL10-deficient chickens, enhanced clearance of the pathogens was associated with elevated transcription of pro-inflammatory genes and increased infiltration of inflammatory cells into gut mucosa. In IL10-deficient chickens challenged with the parasiteEimeria tenella,pathogen clearance was accelerated but caecal lesions were more severe and weight gain was compromised. Neither the heterozygous IL10 knockout nor a homozygous IL10 enhancer mutation had a major effect on pathogen clearance or inflammation in any of the challenge models. Our findings highlight the intrinsic compromise in mucosal immune response and have important implications for the development of strategies to combat avian and zoonotic pathogens in poultry.
Small molecule promoters of endogenous lipid droplet accumulation drive lysophagy
Authors: Vechalapu Sai Kumari , Duraisamy Santhosh , Senthil Sathyapriya , Kumar Rakesh , Ajnar Deepa , Draksharapu Apparao , Kumar Suresh , Allimuthu Dharmaraja 
Published: January 2025

AbstractLipid droplets (LDs) play a central role in regulating metabolism in stress-induced conditions, including one triggered by nutrient deprivation. Unravelling the protein networks involved in the biogenesis of LDs and their causative and functional roles in health and disease continue to evolve. To this cause, genetic manipulation of the lipid metabolic network or supplementation of high fat diet/ oleic acid (OA) are the traditional routes for voluntarily triggering LDs formation in cells and animals. We developed a screening platform for the identification of new LDs inducers, and our primary screening of various fatty acids identified linoleic acid (LOA, DUFA) as a better tool than OA (MUFA) in promoting LDs formation. The screening and validation discovered new small molecule-based tools for promoting a rapid organization of endogenous lipids into droplets in multiple cell types. Notably, our mass spectral lipidomics analysis presented the overproduction of phosphatidylcholines and small triglycerides, a hallmark of LDs. Mechanistic investigations of our lead molecules highlighted lipid peroxidation and ATP depletion through mitochondrial impairment in cells, which could serve as chemical cues for driving the fusion of cellular lipids into LDs. Finally, we uncovered the abrupt levels of LDs formation induced by our molecules promoted lysophagy in cancer cells to prevent their proliferation. Collectively, our work introduces new small molecules as powerful tools for reliably promoting LDs accumulation for studying their roles in biology, and we demonstrate the over accumulation of LDs prevent cancer cell proliferation, movement, and colonization.
Interleukin-34 and debris clearance by mononuclear phagocytes drive retinal pigment epithelium regeneration in zebrafish
Authors: Leach Lyndsay L. , Gonzalez Rebecca G. , Jayawardena Sayuri U. , Gross Jeffrey M. 
Published: January 2025

AbstractThe retinal pigment epithelium (RPE) surrounds the posterior eye and maintains the health and function of the photoreceptors. Consequently, RPE dysfunction or damage has a devastating impact on vision. Due to complex etiologies, there are currently no cures for patients with RPE degenerative diseases, which remain some of the most prevalent causes of vision loss worldwide. Further, owing to a limited capacity for mammalian tissue repair, we know little about how the RPE regenerates. Here, we utilize zebrafish as a model to uncover novel mechanisms driving intrinsic RPE regeneration. We show that interleukin-34 signaling from damaged RPE is required for precisely timed recruitment of mononuclear phagocytes (MNPs) to the injury site. Additionally, we find that cellular debris clearance by MNPs is indispensable for regeneration, as microglia-deficient zebrafish fail to regenerate RPE and photoreceptor tissues. Together, our results establish specific pro-regenerative functions of MNPs after RPE damage.
Tracking the phenology of riverine insect communities using environmental DNA
Authors: Cereghetti Eva , Ajvazi Xhesida , Keck François , Patrignani Andrea , Tartini Nicolò , Altermatt Florian , Carraro Luca 
Published: January 2025

ABSTRACTAquatic insects are iconic and ecologically highly relevant inhabitants of riverine ecosystems. They are also often the target of monitoring programs to assess the ecological status of these lotic habitats. Environmental DNA (eDNA) techniques have been widely and successfully implemented to investigate freshwater insects and other macroinvertebrates. Commonly, such monitoring is conducted at one or two timepoints per year, despite the known strong seasonality and phenology of aquatic insects. Here, we assessed if and how eDNA can capture the temporal changes of the orders Ephemeroptera (mayflies), Plecoptera (stoneflies), Trichoptera (caddisflies) and Diptera (true flies). We carried out eDNA sampling at roughly monthly intervals from April to October at 25 sites across a whole river catchment in the northeastern part of Switzerland. We found pronounced, cyclic phenological trends in all orders but Trichoptera: the communities diverged from spring to summer and then in fall gradually returned closer to the spring state. The four orders exhibited different predominance in gains or losses of species detection throughout this time interval. Lastly, we found that field replicates, despite showing a relatively high local stochasticity, were able to provide a more complete assessment of aquatic communities and could thus be used as a proxy for the frequency of observation of a species through the seasons. In fact, this approach yielded comparable temporal patterns to the ones extracted from the Global Biodiversity Information Facility (GBIF). Overall, our findings demonstrate that eDNA techniques can be used to reveal intra-annual dynamics of aquatic insects. Given the current necessity to assess and monitor the biodiversity status of ecosystems, we therefore show that eDNA methods are a viable option to obtain a deeper understanding of the structuring of freshwater communities over time.
Optimization of a maize rapid cycle breeding scheme using the Modular Breeding Program Simulator (MoBPS)
Authors: Pook Torsten , Tost Mila Leonie , Simianer Henner 
Published: January 2025

AbstractIn recent years, the turnover of plant breeding has substantially increased as the use of genomic information allows for earlier selection and the integration of controlled growing environments reduces time to reach a particular growing stage. However, high generation turnover and intensive selection of lines before own yield trials are performed come at the risk of a drastic reduction of genetic diversity paired with lower prediction accuracies. To this end, we investigate strategies to cope with these challenges in a maize rapid cycle breeding scheme using stochastic simulations using the software MoBPS. We find that genetic gains soon reach a plateau when only the original breeding material is phenotyped. Updating the training data set via additional phenotyping of crosses or doubled haploid lines ensures long-term progress with a gain of 6.80 / 6.95 genetic standard deviations for the performance as a cross /per seafter 30 cycles of breeding compared to 3.40 / 4.28 without additional phenotyping. Adding genetic material with comparable genetic level and novel diversity from outside the breeding material led to a further increase to 9.34 / 7.89 genetic standard deviations. In particular, for the management of genetic diversity, further additions to the breeding scheme are analyzed to optimize the number of selected lines per cycle and to account for the relatedness of F2 plants in the selection using the software AlphaMate. Finding a balance between genetic gains and diversity is important for a given time frame. MoBPS provides a tool for the quantification of these effects and provides solutions specific to the respective breeding program.
Gibberellin enhances germination ofNolana mollisandHeliotropium pycnophyllumseeds
Authors: van den Brink Liesbeth , Mai Melissa H , Henneberg Lorenz , Ecke Margret , Canessa Rafaella 
Published: January 2025

AbstractDesert plants often exhibit seed dormancy, which enables seeds to wait out unfavorable conditions and germinate when there is enough water for the seedling to establish securely. Here, we tested several dormancy-breaking mechanisms forNolana mollisandHeliotropium pycnophyllum, including storage temperature, scarification, hormones, germination temperature, and light cycles during germination. For both species, gibberellin enhanced germination significantly. All other treatments, or combinations of treatments, had no significant effect. Our results can be applied to restoration efforts in arid areas, or in urban areas in arid climates, where the use of native species reduces watering necessities.
Separate, Separated and Together: the Transcriptional Program of theClostridium acetobutylicum- Clostridium ljungdahliisyntrophy leading to interspecies cell fusion
Authors: Willis Noah B. , Papoutsakis Eleftherios T. 
Published: January 2025

ABSTRACTSyntrophic cocultures (hitherto assumed to be commensalistic) ofClostridium acetobutylicumandClostridium ljungdahlii, whereby CO2and H2produced by the former feeds the latter, result in interspecies cell fusion involving large scale exchange of protein, RNA and DNA between the two organisms. Although mammalian cell fusion is mechanistically dissected, the mechanism for such microbial-cell fusions is unknown. To start exploring this mechanism, we used RNA sequencing to identify genes differentially expressed in this coculture using two types of comparisons. One type compared coculture to the two monocultures, capturing the combined impact of interactions through soluble signals in the medium and through direct cell-to-cell interactions. The second type compared membrane separated versus unseparated cocultures, isolating the impact of interspecies physical contact. While we could not firmly identify specific genes that might drive cell fusion, consistent with our hypothesized model for this interspecies microbial cell fusion, we observed differential regulation of genes involved inC. ljungdahlii’sautotrophic Wood-Ljungdahl-Pathway metabolism and genes of the motility machinery. Unexpectedly, we also identified differential regulation of biosynthetic genes of several amino acids, and notably of arginine and histidine. We verified that they are produced byC. acetobutylicumand are metabolized byC. ljungdahliito its growth advantage. These and other findings, and notably upregulation ofC. acetobutylicumribosomal-protein genes, paint a more complex syntrophic picture and suggest a mutualistic relationship, whereby beyond CO2and H2,C. acetobutylicumfeedsC. ljungdahliiwith growth boosting amino acids, while benefiting from the H2utilization byC. ljungdahlii.IMPORTANCEThe construction and study of synthetic microbial cocultures is a growing research area due to the untapped potential of defined multi-species industrial bioprocesses and the utility of defined cocultures for generating insight into complex, undefined, natural microbial consortia. Our previous work showed that coculturingC. acetobutylicumandC. ljungdahliileads to a unique metabolic phenotype (production of isopropanol) and heterologous cell fusion events. Here, we used RNAseq to explore genes involved in and impacted by these fusions. First, we compared gene expression in coculture to each individual monoculture. Second, we utilized a transwell system to compare gene expression in mixed cocultures to cocultures with both species physically separated by a permeable membrane, isolating the impact of interspecies “touching” on the transcriptome. This study deepens our mechanistic understanding of theC. acetobutylicum-C. ljungdahliicoculture phenotype, laying the groundwork for reverse genetic studies of heterologous cell fusion inClostridiumcocultures.
Association between TG/HDL-C and depression: Results from the NHANES, 2005-2020
Authors: Tang Xuemiao , He Qiuhua , Yang Na , Fu Qiang 
Published: January 2025

AbstractLipid profile disturbances are frequently observed in depressive patients. Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) can be reflective of the level of blood lipids. However, it remains unclear whether higher TG/HDL-C increases the risk of depression. This study aimed to investigate the association between TG/HDL-C and depression. In this cross-sectional study, 19,297 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2020. A weighted multivariable logistic regression model, restricted cubic spline regression model and threshold effect analysis were used to explore the association and dose-response relationship of TG/HDL-C with depression risk in the total population and subgroups. A total of 19,297 participants who had complete data on TG/HDL-C and depression measurement were included in this study (mean age 50 years, 51% female). Participants with depression had higher TG/HDL-C than those without depression. TG/HDL-C was associated with an increased risk of depression after adjusting for all covariates (in model 3: OR = 1.12, 95% CI: 1.03-1.21,P= 0.005). Moreover, a nonlinear J-shaped relationship was observed between TG/HDL-C ratio and the risk of depression, with an inflection point of 0.402 by threshold effect analysis. These findings indicate that TG/HDL-C has a J-shaped association with the risk of depression.
Improving Diagnostic Accuracy of Routine EEG for Epilepsy using Deep Learning
Authors: Lemoine Émile , Toffa Denahin , Xu An Qi , Tessier Jean-Daniel , Jemel Mezen , Lesage Frédéric , Nguyen Dang K. , Bou Assi Elie 
Published: January 2025

AbstractBackground and ObjectivesThe diagnostic yield of routine EEG in epilepsy is limited by low sensitivity and the potential for misinterpretation of interictal epileptiform discharges (IEDs). Our objective is to develop, train, and validate a deep learning model that can identify epilepsy from routine EEG recordings, complementing traditional IED-based interpretation.MethodsThis is a retrospective cohort study of diagnostic accuracy. All consecutive patients undergoing routine EEG at our tertiary care center between January 2018 and September 2019 were included. EEGs recorded between July 2019 and September 2019 constituted a temporally shifted testing cohort. The diagnosis of epilepsy was established by the treating neurologist at the end of the available follow-up period, based on clinical file review. Original EEG reports were reviewed for IEDs. We developed seven novel deep learning models based on Vision Transformers (ViT) and Convolutional Neural Networks (CNN), training them to classify raw EEG recordings. We compared their performance to IED-based interpretation and two previously proposed machine learning methods.ResultsThe study included 948 EEGs from 846 patients (820 EEGs/728 patients in training/validation, 128 EEGs/118 patients in testing). Median follow-up was 2.2 years and 1.7 years in each cohort, respectively. Our flagship ViT model, DeepEpilepsy, achieved an area under the receiver operating characteristic curve (AUROC) of 0.76 (95% CI: 0.69–0.83), outperforming IED-based interpretation (0.69; 0.64–0.73) and previous methods. Combining DeepEpilepsy with IEDs increased the AUROC to 0.83 (0.77–0.89).DiscussionDeepEpilepsy can identify epilepsy on routine EEG independently of IEDs, suggesting that deep learning can detect novel EEG patterns relevant to epilepsy diagnosis. Further research is needed to understand the exact nature of these patterns and evaluate the clinical impact of this increased diagnostic yield in specific settings.
Wearable-based digital biomarker provides a valid alternative to traditional clinical measures for post-stroke upper-limb motor recovery
Authors: Wang Ryan , Lang Catherine E. , Stoykov Mary E. , Bonato Paolo , Lee Sunghoon I. 
Published: January 2025

AbstractExisting clinical assessments for upper-limb motor rehabilitation post-stroke pose limitations as endpoints for clinical trials. This study aims to develop a wearable-based digital biomarker for assessing motor recovery using accelerometer data collected in naturalistic environments. The study analyzed approximately 23,000 hours of data from 215 participants, including subacute and chronic stroke survivors and healthy individuals. A novel analytical approach decomposed continuous accelerometer data into a lower-level unit of motor behaviors called movement segments, from which key features were extracted and aggregated using a linear mixed-effects model to produce a composite biomarker. The resulting digital biomarker demonstrated excellent interpretability, reliability, concurrent validity, discriminant validity, known-group validity, and responsiveness, enabling a nearly 66% reduction in the required sample size for clinical trials compared to traditional measures. These findings highlight its potential as a low-burden, scalable assessment tool for upper-limb motor recovery, with applications in both clinical trials and routine clinical practice.
Estradiol-based Menopausal Hormone Therapy is associated with improved episodic and prospective memory scores in the Canadian Longitudinal Study of Aging
Authors: Puri Tanvi A. , Gravelsins Laura , Alexander Madeline Wood , McGovern Andrew J. , Duarte-Guterman Paula , Rabin Jennifer S. , Murphy Kelly J. , Galea Liisa A.M. 
Published: January 2025

AbstractIntroductionMenopause and menopausal hormone therapy (MHT) can influence cognition in postmenopausal women, but previous literature remains equivocal about their effects. MHT varies based on formulation and route of administration, both of which influence dose of estradiol (E2), the estrogen with the greatest affinity to the estrogen receptor. Transdermal E2 avoids hepatic conversion and results in higher plasma levels of E2 than oral E2 formulations. The cognitive domains of executive functions, episodic memory and prospective memory are diminished with age, but may be differentially sensitive to MHT, dependent on the brain regions recruited during the task. There is a lack of research investigating the effects of the age of menopause and estradiol (E2)-based MHT on different cognitive domains.MethodsUsing baseline data from the Canadian Longitudinal Study of Aging, we examined the associations between age of menopause and E2 based MHT on performance in three cognitive domains: episodic memory, prospective memory, and executive functions. Our cohort included 7,251 postmenopausal women who were cognitively healthy, with models adjusted for age, education, and body mass index.ResultsEarlier age at menopause was significantly associated with lower scores across all cognitive domains. However, for the executive functions domain, an earlier age of menopause was associated with lower scores only in those with grand parity (4 or more children) and there was a greater effect size among APOE ε4 carriers. We found that transdermal E2 was associated with higher episodic memory scores, whereas oral E2 was associated with higher prospective memory scores compared to no MHT. Neither administration route significantly affected executive function.ConclusionThese results highlight the differential effects of E2-based MHT depending on route of administration and cognitive domain, and underscore the importance of considering age of menopause and individual characteristics such as reproductive history and genotype status. This work provides clarity to inconsistencies in the literature and informs the development of precision medicine approaches for cognitive aging in postmenopausal people.