bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic state and gene expression remain stable after CRISPR/Cas-mediated chromosomal inversions
Authors: Khosravi Solmaz , Hinrichs Rebecca , Rönspies Michelle , Haghi Reza , Puchta Holger , Houben Andreas 
Published: October 2024

AbstractInArabidopsis thaliana,the chromosome arms are DNA-hypomethylated and enriched in the euchromatin-specific histone mark H3K4me3. In contrast, pericentromeric regions are DNA-hypermethylated and enriched in H3K9me2. In order to investigate how chromosomal location affects epigenetic stability and gene activity, we induced two differently-sized inversions by CRISPR/Cas and introduced heterochromatic, pericentric sequences into an euchromatic chromosomal arm. The epigenetic status of the lines was investigated by whole genome bisulfite sequencing and chromatin immunoprecipitation. Additionally, we studied the effect of the chromosomal inversions on gene expression. Our analysis revealed that both inversions affected neither the global distribution of eu- and heterochromatin-specific histone marks nor the global DNA methylation landscape. However, minor epigenetic changes were found across the entire genome. Importantly, the inverted chromosome regions and their border regions did not change their epigenetic profile. The transcription analysis of both inversion lines revealed that 0.5 - 1 % of genes were differentially expressed across the entire genome. However, the expression activity of those genes encoded by the inverted segments, and located around the cutting sites of CRISPR/Cas was less affected. Thus, gene expression levels and the epigenetic landscape remain preserved following engineered chromosomal restructuring, at least in the following generations.
Neuropeptide Dynamics Coordinate Layered Plasticity Mechanisms Adapting Drosophila Circadian Behavior to Changing Environment
Authors: Chatterjee Abhishek , De Joydeep , Martin Béatrice , Chélot Elisabeth , Rouyer François 
Published: October 2024

AbstractThe Drosophila brain contains distinct sets of circadian oscillators responsible for generating the morning and evening bouts of locomotor activity, giving rise to a bimodal rest-activity pattern in light-dark cycles. We lack a mechanistic understanding of how environmental changes reshape this daily profile of rest-activity pattern. Here, we uncover a seasonal switch mechanism that remodels the evening bout of activity. Under summer-like conditions, an environment favored by fruit flies in temperate climates, levels of the PDF neuropeptide diminish, triggering a cascade. Lowered PDFR signaling disinhibits GSK3/SGG to advance the evening output. Upon sensing PDF loss, the neural activity weakens in the DN1p-SIFacircuit, responsible for promoting afternoon rest; leading to an earlier appearance of the evening peak. At the same time, the functional connections from DN1p to LNd oscillators strengthen, consequently handing over the evening pacemaker role to the DN1ps. Taken together, our findings elucidate how environment-induced changes in PDFR signaling tip the balanced output of the clock network, aligning daily rhythms with seasonal time. Neuropeptide-driven parallel adjustment of clock circuitry and clock protein functioning likely represents a conserved strategy across animal species, enabling them to adapt their daily behavior to seasonal changes throughout the year.
Uniaxial force modifies the length of the mammary ductal network and the orientation of ducts during pubertal development: Findings from computational modeling and laboratory experiments
Authors: Ulloa Daisy , Temple Kelsey M. , Casey Theresa M. , George Uduak Z 
Published: October 2024

AbstractMammary gland forms an extensive tree-like network of epithelium ducts during puberty. The orientation of the ducts determine the overall shape of the epithelium ductal network which in turn impacts the delivery of milk through the ducts to breastfeeding infants. However, how the orientation of the ducts are specified is not well understood. This study examines if an applied force can regulate the orientation of the epithelium ducts during puberty, in vivo. Exogenous forces were applied continuously to pairs of abdominal number four mammary glands in mice, during pubertal formation of the epithelium ductal network at 5-7 weeks of age. In each mice (n=10), one of the abdominal number four mammary gland was exposed to a uniaxial force (TEN) and the other was exposed to a contralateral (CONTRA) force. Subsequently, microscopy images of the epithelium ductal network for the TEN and CONTRA glands were analyzed and compared to controls to determine differences in ductal orientation. Findings from image-based analysis indicate that uniaxial and contralateral forces increase the length of the ductal network. Though the ductal network were longer in the TEN and CONTRA glands, there were no significant differences in the total cross-sectional area of the ductal network compared to controls. However, the orientation of the epithelium ducts in TEN and CONTRA glands were different compared to controls. In-silico simulations of ductal network formation with a branching and annihilating random walk model predicts that the orientation of the epithelium ducts may significantly alter the length of the ductal network. These findings suggest that the increased length of the ductal network resulted from the changes in the orientation of the epithelium ducts. This study therefore determines that exogeneous mechanical forces may regulate ductal network architecture and orientation of ductal branches in vivo.
Lifespan of male and female APP/PS1 and APPNL-F/NL-Fmouse models of Alzheimer’s disease
Authors: Roberts Hannah , Fang Yimin , Quinn Kathleen , Hill Tiarra , Peck Mackenzie R. , Bartke Andrzej , Hascup Kevin N. , Hascup Erin R. 
Published: October 2024

AbstractAlzheimer’s disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APPNL-F/NL-F) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between within genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in APPNL-F/NL-Fmice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports sexual dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.
Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis
Authors: Parker Morgan E. , Mehta Naren U. , Liao Tzu-Chieh , Tomaszewski William H. , Snyder Stephanie A. , Busch Julia , Ciofani Maria 
Published: October 2024

AbstractIL-17-producing γδ T (Tγδ17) cells are innate-like mediators of intestinal barrier immunity. While Th17 cell and ILC3 plasticity have been extensively studied, the mechanisms governing Tγδ17 cell effector flexibility remain undefined. Here, we combined type 3 fate-mapping with single cell ATAC/RNA-seq multiome profiling to define the cellular features and regulatory networks underlying Tγδ17 cell plasticity. During homeostasis, Tγδ17 cell effector identity was stable across tissues, including for intestinal T-bet+Tγδ17 cells that restrained IFNγ production. However, S. typhimurium infection induced intestinal Vγ6+Tγδ17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORγt downregulation. Multiome analysis revealed a trajectory along Vγ6+Tγδ17 effector conversion, with TIM-3 marking ex-Tγδ17 cells with enhanced type 1 functionality. Lastly, we characterized and validated a critical AP-1 regulatory axis centered around JunB and Fosl2 that controls Vγ6+Tγδ17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion.
NicheFlow: Towards a foundation model for Species Distribution Modelling
Authors: Dinnage Russell 
Published: October 2024

Abstract1. Species distribution models (SDMs) are crucial tools for understanding and predicting biodiversity patterns, yet they often struggle with limited data, biased sampling, and complex species-environment relationships. Here I present NicheFlow, a novel foundation model for SDMs that leverages generative AI to address these challenges and advance our ability to model and predict species distributions across taxa and environments.2. NicheFlow employs a two-stage generative approach, combining species embeddings with two chained generative models, one to generate a distribution in environmental space, and a second to generate a distribution in geographic space. This architecture allows for the sharing of information across species and captures complex, non-linear relationships in environmental space. I trained NicheFlow on a comprehensive dataset of reptile distributions and evaluated its performance using both standard SDM metrics and zero-shot prediction tasks.3. NicheFlow demonstrates good predictive performance, particularly for rare and data-deficient species. The model successfully generated plausible distributions for species not seen during training, showcasing its potential for zero-shot prediction. The learned species embeddings captured meaningful ecological information, revealing patterns in niche structure across taxa, latitude and range sizes.4. As a proof-of-principle foundation model, NicheFlow represents a significant advance in species distribution modeling, offering a powerful tool for addressing pressing questions in ecology, evolution, and conservation biology. Its ability to model joint species distributions and generate hypothetical niches opens new avenues for exploring ecological and evolutionary questions, including ancestral niche reconstruction and community assembly processes. This approach has the potential to transform our understanding of biodiversity patterns and improve our capacity to predict and manage species distributions in the face of global change.
Gut bacteria-derived succinate induces enteric nervous system regeneration
Authors: Aydin Begüm , Mamede Izabela , Cardoso Joana , Deere Julia , Alvarez Yelina , Qiao Shanshan , Sharma Ved P. , Scavuzzo Marissa A. , Donaldson Gregory P. , Guo Chun-Jun , Mucida Daniel 
Published: October 2024

AbstractEnteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion1. Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders2–5. However, the signals and underlying mechanisms of this microbiota–neuron communication are unknown. We studied the effects of microbiota on the recovery of the enteric nervous system after microbial dysbiosis caused by antibiotics. We found that both enteric neurons and glia are lost after antibiotic exposure, but recover when the pre-treatment microbiota is restored. Using murine gnotobiotic models and fecal metabolomics, we identified neurogenic bacterial species and their derived metabolite succinate as sufficient to rescue enteric neurons and glia. Unbiased single-nuclei RNA-seq analysis uncovered a novel neural precursor-like population marked by the expression of the neuronal gene Nav2. Genetic fate-mapping showed that Plp1+ enteric glia differentiate into neurons following antibiotic exposure. In contrast, Nav2+ neurons expand upon succinate treatment and indicate an alternative mode of neuronal regeneration under recovery conditions. Our findings highlight specific microbial species, metabolites, and the underlying cellular mechanisms involved in neuronal regeneration, with potential therapeutic implications for peripheral neuropathies.
Fentanyl Overdose Deaths Decreased Following Scanner Use at Ports-of-Entry
Authors: Miron Oren 
Published: October 2024

AbstractOverdose deaths in the United States surged from 2018 to 2022 due to the smuggling of fentanyl through ports-of-entry. To combat this epidemic, the U.S. used advanced scanners at southern ports-of-entry, which tripled inspections and improved screening, especially since March 2023. Following March 2023, fentanyl domestic seizures decreased by 29% and fentanyl overdose deaths decreased by 35%. Fentanyl overdose deaths decreased in 90% of states and increased only in states that receive fentanyl through ports-of-entry that lack these scanners. If this decrease in overdose deaths continues until November 2025, the death rate would be lower than at the start of the opioid epidemic. These results support urgent funding for advanced scanners at ports-of-entry that lack them.
Intensity of care and the health status of caregivers to elderly rural South Africans
Authors: Matina Sostina S , Manderson Lenore , Gómez-Olivé F. Xavier , Berkman Lisa , Harling Guy 
Published: October 2024

ABSTRACTObjectivesInformal caregivers play an indispensable role in and are often the sole source of care for older adults in low and middle-income settings worldwide. Intensive informal care predicts mortality and morbidity among caregivers in higher-income settings. However, there is limited evidence from poorer settings, including Africa countries, where caregiving is shared widely, including across generations. We therefore investigated caregivers’ health status in rural South Africa.MethodsWe conducted quantitative interviews with all household members and all non-household caregivers aged ≥12 (n=1012) of 106 older adults in rural Mpumalanga, South Africa. We used multivariable regression with care-recipient random intercepts to assess the relationships between four caregiving characteristics and both self-reported chronic conditions and self-reported health status, considering how caregiver age moderated each association.ResultsOver half of all caregivers reported at least one chronic health condition, despite half being aged under 40. Caregivers self-reporting the worst health status provided high hours of care. However, caregivers’ health status was not significantly associated with weekly care quantity or history of caring. Those aged ≥40 who reported being a main caregiver had 52% increased odds of reporting poorer health compared to other same-aged carers (95% confidence interval: 0.99, 2.35), while having more chronic conditions was associated with being expected to act as a sole caregiver more often among caregivers aged ≤39.DiscussionGreater caring responsibilities for older adults were not consistently associated with caregivers’ health in a setting where poor health is common, and caregiving is spread widely. Longitudinal data is necessary to unpack possible explanations of these findings, and to determine whether intensive caregiving speeds downward health trajectories for carers.
Optimisation of a cervical cancer screening model based on self-sampling for human papillomavirus testing
Authors: Besó Delgado María , Ibáñez Cabanell Josefa , Castán Cameo Susana , Mira Solves José Joaquín , Guilabert Mora Mercedes , Vanaclocha Espí Mercedes , Pinto Carbó Marina , Salas Trejo Dolores , Llorens Oscar Zurriaga , Molina-Barceló Ana 
Published: October 2024

AbstractThe use of self-sampling devices in population-based cervical cancer screening programmes (CCSP) is both an opportunity and a challenge in terms of implementation.ObjectiveTo understand the expectations, preferences, and difficulties perceived by women as regards different screening models and self-sampling devices, with the aim of identifying strategies to achieve high CCSP participation rates.MethodsThis study is based on qualitative research techniques, consisting of an individual interview using a questionnaire with semi-structured questions, followed by a group interview. Sessions were held simultaneously with 4 groups (7-8 women aged between 35 and 65). Women assessed various aspects of the programme (information dissemination, invitation, receipt of results, etc.) and five self-sampling devices.ResultsIf screening were carried out via self-sampling, 96.4% of women said they would take the test. Most women preferred to receive information on the CCSP or return their samples at their health centres (86.2% and 86.2%), and the most popular method for receiving both the programme invitation and results is by SMS (58.6%, 65.5%).Simplicity and ease of use are the key features of the device accepted by the largest number of women, the FLOQSwab. Another highly rated feature is the attractive design of the Evalyn Brush, as this was the preferred device of the largest number of women.The existence of other screening programmes that use self-sampling devices (the colorectal cancer prevention programme) is an opportunity as regards acceptance of this new programme. Some women are unsure of how to use the devices correctly.A large number of women accept self-sampling and reveals significant differences in the degree of acceptance of different self-sampling devices. Selecting the most accepted device is key to achieving high CCSP participation rates, and these programmes should be accompanied by adapted information campaigns to reach the most vulnerable groups and ensure equity.
Cross-modality image translation of 3 Tesla Magnetic Resonance Imaging to 7 Tesla using Generative Adversarial Networks
Authors: Diniz Eduardo , Santini Tales , Helmet Karim , Aizenstein Howard J. , Ibrahim Tamer S. 
Published: October 2024

AbstractThe rapid advancements in magnetic resonance imaging (MRI) technology have precipitated a new paradigm wherein cross-modality data translation across diverse imaging platforms, field strengths, and different sites is increasingly challenging. This issue is particularly accentuated when transitioning from 3 Tesla (3T) to 7 Tesla (7T) MRI systems. This study proposes a novel solution to these challenges using generative adversarial networks (GANs)—specifically, the CycleGAN architecture— to create synthetic 7T images from 3T data. Employing a dataset of 1112 and 490 unpaired 3T and 7T MR images, respectively, we trained a 2-dimensional (2D) CycleGAN model, evaluating its performance on a paired dataset of 22 participants scanned at 3T and 7T. Independent testing on 22 distinct participants affirmed the model’s proficiency in accurately predicting various tissue types, encompassing cerebral spinal fluid, gray matter, and white matter. Our approach provides a reliable and efficient methodology for synthesizing 7T images, achieving a median Dice of 6.82%,7,63%, and 4.85% for Cerebral Spinal Fluid (CSF), Gray Matter (GM), and White Matter (WM), respectively, in the testing dataset, thereby significantly aiding in harmonizing heterogeneous datasets. Furthermore, it delineates the potential of GANs in amplifying the contrast-to-noise ratio (CNR) from 3T, potentially enhancing the diagnostic capability of the images. While acknowledging the risk of model overfitting, our research underscores a promising progression towards harnessing the benefits of 7T MR systems in research investigations while preserving compatibility with existent 3T MR data. This work was previously presented at the ISMRM 2021 conference (Diniz, Helmet, Santini, Aizenstein, & Ibrahim, 2021).
The Water, Sanitation, and Hygiene (WASH) for Everyone controlled before-and-after (CBA) trial: trial protocol and baseline results
Authors: Chidziwisano Kondwani , Panulo Mindy , MacLeod Clara , Vignieri Marcella , White Blessings , Ross Ian , Morse Tracy , Dreibelbis Robert 
Published: October 2024

AbstractCommunity-based behaviour change interventions are a common approach to Water, Sanitation, and Hygiene (WASH). Yet, published evaluations of how these interventions work in district-wide approaches are rare. This study reports the baseline characteristics and study design for a trial assessing the effectiveness of a district-level Community-led Total Sanitation (CLTS) intervention compared to the additional integration of local Care Groups on sanitation coverage and use and hygiene behaviours in Chiradzulu District, Malawi.This study is a controlled before-and-after trial with two treatment arms and a control group. Clusters are rural villages in three Traditional Authorities (TAs). One arm receives CLTS and the Care Group Model, one arm receives CLTS only, and one serves as the control group. The trial is part of the wider WASH for Everyone (W4E) project, led by World Vision Malawi which aims to expand access to WASH services across the entire district by 2025. Study participants were selected from the three TAs. Systematic sampling procedures were used to select 20 households per cluster with a total of 1,400 households at both baseline and endline. The primary outcome is sanitation coverage. Secondary outcome measures include sanitation use, safe disposal of child faeces, observed handwashing facility, and Sanitation-related Quality of Life index (SanQoL-5).Baseline results show a no difference for primary and secondary outcomes between arms. We noted low coverage of handwashing facilities with soap and water in all the three arms (i.e., CLTS only = 7%; CLTS and Care Groups = 4%; and control = 10%). Further, there was a slight variation (p= 0.08) in handwashing practice and sanitation coverage among the study arms.The baseline observations indicate a balanced distribution of potential demographic confounders in the trial arms. The trial intervention is under implementation. The evaluation report is expected to be published in 2025.
Effects of Health Education to Reduce Stroke Recurrence by Controlling Modifiable Factors: A Randomized Controlled Trial
Authors: Afrin Mahabuba , Khan Sharif Uddin , Das Subir Chandra , Ehsanul Huq K. A. T. M , Chowdhury Mohammad Shah Jahirul Hoque , Fukuoka Yasuko , Fukushima Yasuko , Moriyama Michiko 
Published: October 2024

ABSTRACTBACKGROUNDHealth education could be an effective measure to prevent stroke recurrence; however, the evidence is still ambiguous. The aim of this study was to evaluate the effectiveness of a health education program among stroke patients and their family caregivers to reduce stroke recurrence.METHODSA parallel (1:1), open-label, prospective randomized controlled trial was conducted at the National Institute of Neuroscience & Hospital in Bangladesh between October 2022 and March 2024. We enrolled stroke patients who were discharged from the inpatient department or attended as an outpatient of the hospital. The primary endpoint was the recurrence rate of stroke within 12 months of intervention. The secondary endpoints were the rate of all adverse events related to stroke that occurred within 12 months of follow-up visits.RESULTSWe analyzed data from 432 patients (216 in each group). We found recurrence was 14 (6.5%) in the IG and 8 (3.7%) in the CG after 28 days of first-stroke attack, and the difference was not significant (p=0.189). We observed stroke-related adverse events 116 (26.9%) (25.0% in IG and 28.7% in CG, p=0.294) including death 95 (22.0%) (18.1% in IG and 25.9% in CG, p=0.041) during 12-month period. Even though stroke patient’s medication adherence was significantly improved at 6-month and 12-month after intervention in IG (p<0.001 and p=0.002, respectively), all events and all causes of death were not significant after adjusted by the severity of stroke (mRS) (p=0.933, p=0.341, respectively).CONCLUSIONSThe findings of this newly approached intervention can be used as the most reliable evidence for epidemiological figures for Bangladesh. Health education could reduce death and enhance medication adherence significantly among stroke patients. This study results suggest the importance of structuring the acute care system and health education programs to integrate into the health system for the management of stroke. However, an accurate diagnostic and follow-up system is crucial.CLINICAL TRIAL REGISTRATIONhttps://clinicaltrials.gov/ct2/show/NCT05520034.