bluuebunny/crossref_metadata_2025_split huggingface dataset:
40 Hz light stimulation restores early brain dynamics alterations and associative memory in Alzheimer’s disease model mice
Authors: Aguilera Matthieu , Mathis Chantal , Herbeaux Karin , Isik Amine , Faranda Davide , Battaglia Demian , Goutagny Romain 
Published: October 2024

AbstractVisual gamma entrainment using sensory stimuli (vGENUS) is a promising non-invasive therapeutic approach for Alzheimer’s disease (AD), showing efficacy in improving memory function. However, its mechanisms of action remain poorly understood. Using young AppNL-F/MAPT double knock-in (dKI) mice, a model of early AD, we examined brain dynamics alterations before amyloid plaque onset. High-density EEG recordings and novel metrics from fields outside neuroscience were used to assess brain dynamics fluidity—a measure of the brain’s ability to transition between activity states. We revealed that dKI mice exhibit early, awake state-specific reductions in brain dynamics fluidity associated with cognitive deficits in complex memory tasks. Daily vGENUS sessions over two weeks restored brain dynamics fluidity and rescued memory deficits in dKI mice. Importantly, these effects built up during the stimulation protocol and persisted after stimulation ended, suggesting long-term modulation of brain function. Based on these results, we propose a “brain dynamics repair” mechanism for vGENUS that goes beyond current amyloid-centric hypotheses. This dual insight - that brain dynamics are both a target for repair and a potential diagnostic tool - provides new perspectives on early Alzheimer’s disease pathophysiology.Significance StatementGamma ENtrainment Using Sensory stimuli (GENUS), involving 40 Hz rhythmic sensory stimulation, shows promise in improving memory function in Alzheimer’s disease (AD). We hypothesized that brain dynamics changes could be detected before plaque onset and modulated by vGENUS. Applying techniques from climate science to EEG recordings in young AD model mice, we found reduced brain dynamics fluidity associated with early cognitive deficits. Two weeks of vGENUS restored brain dynamics and improved memory, with effects persisting post-treatment. These findings challenge the amyloid-centric view of AD, introduce a potential early biomarker, and suggest vGENUS acts by “repairing” brain dynamics. Our approach offers new perspectives on early diagnosis and non-invasive interventions for AD and other neurological disorders with disrupted brain dynamics.
Visual objects refine head direction coding
Authors: Siegenthaler Dominique , Denny Henry , Skromne Carrasco Sofía , Mayer Johanna Luise , Levenstein Daniel , Peyrache Adrien , Trenholm Stuart , Macé Émilie 
Published: October 2024

AbstractAnimals use visual objects to guide navigation-related behaviors, from hunting prey, to escaping predators, to exploring the world. However, little is known about where visual objects are encoded in the mouse brain or how they impact processing in the spatial navigation system. Using functional ultrasound imaging in mice, we conducted a brain-wide screen and identified brain areas that were preferentially activated by images of objects compared to scrambled versions of the same images. While visual cortical areas did not show a significant preference, regions associated with spatial navigation were preferentially activated by visual objects. Electrophysiological recordings in postsubiculum, the primary cortical area of the head direction (HD) system, further confirmed a preference for visual objects, which was present in both HD cells and fast-spiking interneurons. Finally, we found that visual objects dynamically modulated HD cells, selectively increasing firing rates of HD cells aligned with a visual landmark’s direction, while decreasing activity in HD cells coding for other directions. These results reveal that visual objects refine population-level coding of head direction.
Proper reference selection and re-referencing to mitigate bias in single pulse electrical stimulation data
Authors: Huang Harvey , Adkinson Joshua A. , Jensen Michael A. , Hasen Mohammed , Danstrom Isabel A. , Bijanki Kelly R. , Gregg Nicholas M. , Miller Kai J. , Sheth Sameer A. , Hermes Dora , Bartoli Eleonora 
Published: October 2024

AbstractSingle pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminate the pulse-evoked potentials recorded at all other electrodes and influence interpretation of findings. We highlight this specific issue in intracranial EEG datasets from two subjects recorded at separate institutions. We present several intuitive metrics to detect the presence of reference contamination and offer practical guidance on different mitigation strategies. Either switching the reference electrode or re-referencing to an adjusted common average effectively mitigated the reference contamination issue, as evidenced by increased variability in pulse-evoked potentials across the brain. Overall, we demonstrate the importance of clear quality checks and preprocessing steps that should be performed before analysis of single pulse electrical stimulation data.HighlightsA reference electrode close to active tissue can contaminate intracranial EEG signalsInterpretation of pulse-evoked potentials can be biased by reference contaminationLow response variability between channels is indicative of reference contaminationReference contamination can be resolved through data recollection or re-referencing
Space matters: virtual pedestrians with mobility constraints affect individuals’ avoidance behaviours
Authors: Nikmanesh Mohammadamin , Cinelli Michael E. , Marigold Daniel S. 
Published: October 2024

ABSTRACTWalking in urban settings requires people to negotiate crowds. In these situations, people typically want to maintain a level of personal space around themselves. Recent work on one-versus-one interactions demonstrated that whether one of the pedestrians looked distracted or interacted with an object (e.g., stroller, bike) predicted the medial-lateral separation between them as they walked past each other. However, this work did not distinguish between the type of object interaction (or mobility constraint) and thus, it is unclear whether different constraints have different effects on avoidance behaviours. Here we tested the hypothesis that the type of object an approaching pedestrian held or pushed would affect the extent of path deviation, which would also depend on whether that pedestrian was distracted. To address this hypothesis, we created an immersive virtual environment that consisted of a 3.5-m-wide paved urban path. Participants had to walk and avoid colliding with approaching virtual pedestrians that often held a shopping bag or pushed a bike or stroller while looking straight ahead or off to the side as if distracted. Distraction did not affect avoidance behaviours. However, participants increased medial-lateral separation with the virtual pedestrian at the time of crossing when a stroller was present compared to the other mobility constraints. The type of mobility constraint also differentially affected onset of deviation and rate of progression before and after a path deviation. These results support the idea that characteristics of the obstacle to avoid (in this case, a virtual pedestrian) influence collision avoidance behaviours.
Defining Cellular Diversity at the Swine Maternal-Fetal Interface Using Spatial Transcriptomics and Organoids
Authors: McCutcheon Cole R. , Caldwell Allyson , Yang Liheng (Henry) , Crisci Elisa , Pasternak J. Alex , Coyne Carolyn B. 
Published: October 2024

ABSTRACTThe placenta is a dynamic, embryo-derived organ essential for fetal growth and development. While all eutherian mammals have placentas composed of fetal-derived trophoblasts that mediate maternal-fetal exchange, their anatomical and histological structures vary across species due to evolutionary divergence. Despite the cellular heterogeneity of porcine trophoblastsin vivo, understanding the mechanisms driving porcine placental development has been limited by the lack ofin vitromodels replicating this heterogeneity. In this study, we derived swine trophoblast organoids (sTOs) from full-term porcine placentas, retaining key transcriptional signatures ofin vivotrophoblasts. To identify conserved cell populations, we integrated Visium spatial transcriptomics from mid-gestation porcine placentas with single-cell transcriptomics from sTOs. Spatial transcriptomics revealed novel markers of the porcine uterus and placenta, enabling precise separation of histological structures at the maternal-fetal interface. The integration of tissue and sTO transcriptomics showed that sTOs spontaneously differentiate into distinct trophoblast populations, with conserved gene expression and cell communication programs. These findings demonstrate that sTOs recapitulate porcine placental trophoblast populations, offering a powerful model for advancing placentation research. Our work also provides a spatially resolved whole-transcriptome dataset of the porcine maternal-fetal interface, opening new avenues for discoveries in placental development, evolution, and health across mammals.
Spatial memory in Alzheimer’s disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330
Authors: Wong Shi Quan , Ouellette Adia , McNamara Avery , Tam Rachel A. , Alexandrov Alexander , Nawrocik-Madrid Acacia , Sanchez Jesus J. , Ginsburg Brett C. , Andrade Arturo A. , Lapierre Louis R. 
Published: October 2024

ABSTRACTThe proteostatic decline in Alzheimer’s disease is well established and improvement in proteostasis could potentially delay cognitive impairment. One emerging entry point to modulate proteostasis is the regulation of nucleo-cytoplasmic partitioning of proteins across the nuclear pore via karyopherins. The nuclear exportin XPO1 is a key regulator of proteostasis by driving the assembly of ribosomes and by modulating the process of autophagy. We recently found that XPO1 inhibitor KPT-330 (Selinexor), an FDA approved drug against multiple myelomas, enhances proteostasis, leading to benefits in models of neurodegenerative diseases inC. elegansandDrosophila. Here, we find that KPT-330 increases autophagy in murine neuronal cells and improves spatial memory performance in a murine model of Alzheimer’s disease (5XFAD). Unexpectedly, general amyloid deposition in several brain regions was significantly increased by KPT-330, but specific regions, especially the thalamus, displayed significantly lower deposition, suggesting that XPO1 inhibition has regional-specific effects on proteostasis and amyloid plaque formation. Altogether, we conclude that XPO1 inhibition can improve cognition via spatially-specific reductions in amyloid deposition.
Benefits of combining individual and small group assessments as an instructional strategy
Authors: Arini Gabriel Santos , de Souza Almeida Israel , Torres Bayardo Baptista 
Published: October 2024

AbstractAssessment is an essential curricular component despite being often seen only as a performance metric resource. However, its full potential can be harnessed if it is used as a formative instrument. The present study evaluated the benefits of combining individual and group assessments. Students’ perceptions of this type of strategy, assessed through a Likert scale questionnaire and semi-structured interviews, showed that students acknowledge the benefits of this procedure. We then carried out a dual assessment in an active learning environment. Students were given individual written tests and completed the same test immediately after, but now in a group. The average group scores were higher than the average individual scores, even for students who scored the highest within a group. Put together, these results indicate combining individual and group assessments can be an effective teaching tool in addition to simply measuring student performance.
Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease
Authors: Tsourmas Kate I. , Butler Claire A. , Kwang Nellie E. , Sloane Zachary R. , Dykman Koby J. G. , Maloof Ghassan O. , Prekopa Christiana A. , Krattli Robert P. , El-Khatib Sanad M. , Swarup Vivek , Acharya Munjal M. , Hohsfield Lindsay A. , Green Kim N. 
Published: October 2024

ABSTRACTLysosomal storage disorders (LSDs) are a large disease class involving lysosomal dysfunction, often resulting in neurodegeneration. Sandhoff disease (SD) is an LSD caused by a deficiency in the β subunit of the β-hexosaminidase enzyme (Hexb). AlthoughHexbexpression in the brain is specific to microglia, SD primarily affects neurons. To understand how a microglial gene is involved in maintaining neuronal homeostasis, we demonstrated that β-hexosaminidase is secreted by microglia and integrated into the neuronal lysosomal compartment. To assess therapeutic relevance, we treated SD mice with bone marrow transplant and colony stimulating factor 1 receptor inhibition, which broadly replacedHexb-/-microglia withHexb-sufficient cells. This intervention reversed apoptotic gene signatures, improved behavior, restored enzymatic activity andHexbexpression, ameliorated substrate accumulation, and normalized neuronal lysosomal phenotypes. These results underscore the critical role of myeloid-derived β- hexosaminidase in neuronal lysosomal function and establish microglial replacement as a potential LSD therapy.
An implementation study of the service model for genetic risk-based stratified breast cancer screening – Estonian results of the BRIGHT project
Authors: Tamm Madli , Padrik Peeter , Ojamaa Kristiina , Paas Anette , Lepland Anni , Kruuv-Käo Krista , Leitsalu Liis , Sõber Siim , Roht Laura , Pajusalu Sander , Kahre Tiina , Padrik Anna , Pindmaa Jagnar , Luga Kadri , Rootslane Ly , Ilves Anne , Ulp Sulev , Kallak Kersti , Tihamäe Ave-Triin , Tõnisson Neeme 
Published: October 2024

AbstractBreast cancer (BC) remains the most common malignant tumor site and the leading cause of cancer-related deaths in women despite the wide availability of screening programs and personalized treatment options. The BRIGHT study tested a genetic risk-based personalized BC screening service model in women younger than 50 years, using telemedicine and home-based testing. Participants underwent polygenic risk score and monogenic pathogenic variant testing. This type of screening model demonstrated feasibility, clinical utility, and acceptability. It has the potential to enhance BC screening programs, particularly for younger women and those at higher genetic risk, while avoiding unnecessary interventions for low-risk individuals.
The role of the microbiota in respiratory virus-bacterial pathobiont relationships in the upper respiratory tract
Authors: Kelly Matthew S. , Shi Pixu , Boiditswe Sefelani C. , Qin Emily , Steenhoff Andrew P. , Mazhani Tiny , Patel Mohamed Z. , Cunningham Coleen K. , Rawls John F. , Luinstra Kathy , Gilchrist Jodi , Maciejewski Julia , Hurst Jillian H. , Seed Patrick C. , Bulir David , Smieja Marek 
Published: October 2024

ABSTRACTThe mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants in Botswana, we performed a detailed analysis of factors that influence the dynamics of bacterial pathobiont colonization during infancy. We quantify the extent to which viruses increase the acquisition ofHaemophilus influenzae,Moraxella catarrhalis, andStreptococcus pneumoniae. We provide evidence of cooperative interactions between these pathobionts while identifying host characteristics and environmental exposures that influence the odds of pathobiont colonization during early life. Using 16S rRNA gene sequencing, we demonstrate that respiratory viruses result in losses of putatively beneficialCorynebacteriumandStreptococcusspecies that are associated with a lower odds of pathobiont acquisition. These findings provide novel insights into viral-bacterial relationships in the URT of direct relevance to respiratory infections and suggest that the URT bacterial microbiota is a potentially modifiable mechanism by which viruses promote bacterial respiratory infections.
Moonlit Misconceptions: A South Florida Veterans’ Hospital Perspective on Full Moon Emergency Room Visits
Authors: VanMeter David J. , Strebel Timothy S. , Mastorides Stephen M. , Borkowski Andrew A. 
Published: October 2024

ABSTRACTThe belief that the full moon influences human behavior and health outcomes has persisted for centuries despite limited scientific evidence. This study examined whether there is a correlation between the lunar cycle and emergency department (ED) visits and hospital admissions among veterans in South Florida from 2013-2023. Data on 465,838 ED visits resulting in 110,640 admissions and moon illumination fraction data were analyzed. The results showed no significant difference in the mean number of ED visits, admissions, or percentage of visits resulting in admission across different moon illumination fractions, including full moons. While some past studies have suggested links between the lunar cycle and health conditions like seizures and psychiatric issues, this study found no association between the full moon and ED utilization patterns in the South Florida veteran population over an 11-year period. The findings contradict the long-standing belief about the lunar effect on hospital services and do not support adapting staffing or resources based on the moon’s phase.
Infant gonadotropins predict spontaneous puberty in girls with Turner syndrome
Authors: Sawyer Alexandra , Bothwell Samantha , Swenson Karli , Travers Sharon , Davis Shanlee 
Published: October 2024

AbstractIntroductionHypergonadotropic hypogonadism is a characteristic clinical manifestation of Turner syndrome (TS). While up to 30% and 20% of people with TS will have spontaneous thelarche and menarche respectively, there is a lack of evidence to predict who will retain sufficient ovarian function to achieve these outcomes. The aim of this study was to determine if follicle-stimulation hormone (FSH) and/or luteinizing hormone (LH) concentrations measured in infancy would accurately predict later spontaneous thelarche or menarche.MethodsPatients with a diagnosis of Turner syndrome with FSH and/or LH clinically measured prior to three years of age and now ≥10 years of age with documented pubertal assessment were included (n=33). Differences in infant gonadotropin values were determined for patients with vs without spontaneous thelarche/menarche using Kruskal-Wallis tests. The optimal threshold of infant LH and FSH to predict spontaneous thelarche and menarche was then determined by maximizing the sum of sensitivity and specificity.ResultsThe prevalence of spontaneous thelarche and menarche were 21.2% and 15.2% respectively. An infant LH value greater than 0.5 mIU/mL predicted lack of spontaneous thelarche with an estimated accuracy of 94% and lack of spontaneous menarche with an estimated accuracy of 96%. An infant FSH value greater than 37.4 mIU/mL predicted lack of lack of spontaneous thelarche with an accuracy of 97% and lack of spontaneous menarche with an accuracy of 100%.ConclusionInfant gonadotropin concentrations accurately predict spontaneous later thelarche and menarche for persons with TS.
Association between TikTok use and the development of eating disorders in young Colombian adults between 18 and 25 years of age
Authors: Restrepo-Escudero Laura , McCormick Silvia , Cuevas Maria Isabel , Mosquera Sara , Vásquez Mariana , Correa Maria José , Patiño Maria Camila , Reyes Pablo , González Ballesteros Lina Maria 
Published: October 2024

AbstractBackgroundVisual and appearance-based social media platforms like TikTok can establish unrealistic beauty standards and self-esteem issues, leading to the development of eating disorders (EDs). This study aims to evaluate the association between TikTok usage and the presence of EDs risk behaviors and body dissatisfaction among Colombian young adults aged between 18 and 25 years.MethodsA cross-sectional descriptive study was conducted via an online survey through snowball sampling with 171 participants. The survey assessed demographic variables, social media use, content consumption, EDs risk behaviors, and body dissatisfaction through validated tools. Non-parametric tests and regression models were used for the data analysis.ResultsTikTok users showed significantly higher scores in ED risk behaviors (M = 14.91) and body dissatisfaction (M = 21.9) compared to non-users. Contributory usage, particularly collaborative content creation, was the most associated with increased risk. The multivariate regression model for ED risk explained 3% of the variance, while TikTok use accounted for 30% of the variance in the model for body dissatisfaction.DiscussionOur study found a significant association between TikTok use and the development of ED risk behaviors and body dissatisfaction. These findings align with previous research and highlight the need for interventions that encourage mindful social media consumption.
A Normal Forced Vital Capacity Does Not Reliably or Equitably Exclude Restriction
Authors: Moffett Alexander T. , Balasubramanian Aparna , McCormack Meredith C. , Aysola Jaya , Halpern Scott D. , Weissman Gary E. 
Published: October 2024

AbstractBackgroundEuropean Respiratory Society and American Thoracic Society (ERS/ATS) guidelines for pulmonary function test (PFT) interpretation recommend the use of a normal forced vital capacity (FVC) to exclude restriction. However, this recommendation is based upon a single study from 1999, which was limited to White patients, and used race-specific reference equations that are no longer recommended by ERS/ATS. We sought to reassess the support for this recommendation by calculating the negative predictive value (NPV) of a normal FVC in a diverse, multicenter cohort using race-neutral reference equations.MethodsWe interpreted PFTs performed between 2000 and 2023 in two academic medical systems and in a national electronic health record (EHR) database. We calculated the NPV of a normal FVC to exclude restriction overall and among pre-specified racial and ethnic groups.ResultsWe included PFTs from 85 990 patients. The prevalence of restriction was 35.1%. The overall NPV of a normal FVC to exclude restriction was 80.5% (95% CI 80.1% to 80.8%), compared to an NPV of 97.6% cited in support of ERS/ATS guidelines. The NPV ranged from 65.2% (95% CI 64.4% to 66.0%) among non-Hispanic Black patients to 85.9% (95% CI 85.6% to 86.3%) among non-Hispanic White patients. This difference was largely attributable to lower FVC z-scores among non-Hispanic Black patients.ConclusionsThe NPV of a normal FVC is lower than has been previously reported and varies by race and ethnicity. The approach to PFT interpretation recommended by ERS/ATS guidelines results in the under-recognition of restriction, particularly among non-Hispanic Black patients.