bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning to Predict Future Cognitive Decline: A Multimodal Approach Using Brain MRI and Clinical Data
Authors: Chattopadhyay Tamoghna , Senthilkumar Pavithra , Ankarath Rahul H. , Patterson Christopher , Gleave Emma J. , Thomopoulos Sophia I. , Huang Heng , Shen Li , You Lei , Zhi Degui , Thompson Paul M. 
Published: February 2025

AbstractPredicting the trajectory of clinical decline in aging individuals is a pressing challenge, especially for people with mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, or vascular dementia. Accurate predictions can guide treatment decisions, identify risk factors, and optimize clinical trials. In this study, we compared two deep learning approaches for forecasting changes, over a 2-year interval, in the Clinical Dementia Rating scale ‘sum of boxes’ score (sobCDR). This is a key metric in dementia research, and scores range from 0 (no impairment) to 18 (severe impairment). To predict decline, we trained a hybrid convolutional neural network that integrates 3D T1-weighted brain MRI scans with tabular clinical and demographic features (including age, sex, body mass index (BMI), and baseline sobCDR). We benchmarked its performance against AutoGluon, an automated multimodal machine learning framework that selects an appropriate neural network architecture. Our results demonstrate the importance of combining image and tabular data in predictive modeling for clinical applications. Deep learning algorithms can fuse image-based brain signatures and tabular clinical data, with potential for personalized prognostics in aging and dementia.
Cortical thinning in temporal pole, a core region in Alzheimer’s disease, in non-demented, middle-agedAPOE-ε4 andPICALM-AA/AG carriers
Authors: Dzianok Patrycja , Wojciechowski Jakub , Wolak Tomasz , Kublik Ewa 
Published: February 2025

AbstractThe symptoms of Alzheimer’s disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal cortex. However, the influence of genetic risk on cortical thickness in non-demented individuals prior to disease onset remains unclear. This study aimed to explore the relationship between two AD risk genes (APOE/PICALM) and cortical thickness in selected regions of interest (ROIs) in non-demented, middle-aged individuals. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45±3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their AD risk. Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred as “the cortical signature of AD” in previous studies.APOE-ε4 withPICALM-AA/AG carriers (A+P-) are characterized by a thinner cortex in the right temporal pole compared to non-carriers, controlling for sex. No other differences in cortical thickness were found in the selected ROIs. The direction of the findings aligns with existing literature reporting cortical thinning in amyloid-positive individuals, as well as in patients with mild cognitive impairment and Alzheimer’s disease when compared to control groups.
Layer connective fields from ultrafast resting-state fMRI differentiate feedforward from feedback signaling
Authors: Carvalho Joana , Fernandes Francisca F. , Valente Mafalda , Haak Koen V. , Shemesh Noam 
Published: February 2025

AbstractDeciphering the directionality of information flow in cortical circuits is essential for understanding brain dynamics, learning, and neuroplasticity after injury. However, current non-invasive methods cannot distinguish feedforward (FF) from feedback (FB) signals across entire networks, including deep brain regions. Here, we present a novel approach combining ultrafast fMRI with a Layer-based Connective Field (lCF) model to disentangle FF from FB signaling. Our findings reveal that lCF size, an indicator of spatial information integration, differentiates FF and FB activity through distinct layer-specific connectivity patterns during spontaneous activity, challenging the notion that FF signals are solely stimulus-driven. FF connectivity follows an inverted U-shape, peaking in layer IV, while FB exhibits a U-shaped pattern, with peaks in layers I and VI. These profiles generalize across sensory pathways (visual, somatosensory, and motor) and reveal injury-induced network reorganization, such as LGN bypassing V1 to provide direct FF input to higher visual areas.
Astrocytic activation of EMMPRIN contributes to their pathological phenotype in ALS
Authors: Edozie Gloria Nwamaka , Bélanger Jasmine , Pigeyre Shanna , Gosselin Ariane , Boyer Marion , Godin Antoine G. , Pozzi Silvia 
Published: February 2025

AbstractAmyotrophic Lateral Sclerosis (ALS) is a fatal disease characterised by the degeneration of upper and lower motoneurons. Onset and progression of the disease are determined by both cell-autonomous neuronal dysfunctions and non-cell-autonomous factors, mainly due to activation of glial cells such as astrocytes and microglia.The Extracellular Matrix Metalloproteinases INducer (EMMPRIN), a glycoprotein expressed by various cell types including neurons, is the major activator of matrix metalloproteinases (MMPs) synthesis and release. EMMPRIN activation can be induced by peptidyl-prolyl isomerase A (PPIA), a chaperone protein with cis/trans isomerase activity, that exhibits cytokine- and chemokine-like behaviour. Previous studies showed that PPIA is highly released in the cerebrospinal fluid (CSF) of ALS patients and animal models where, by activating EMMPRIN on motoneurons, induces neuronal death.Here, we show that EMMPRIN is expressed also by astrocytes, suggesting this cell type as sensitive as motoneurons to PPIA-mediated EMMPRIN activation. We observed that that PPIA-mediated EMMPRIN activation prompt astrocytes toward a pro-inflammatory profile. Interestingly, we found that this pathogenic profile can be reverted by an anti-EMMPRIN antibody. Finally, we provide evidence that the activation of EMMPRIN is relevant for mutant SOD1 and TDP-43 conditions.In conclusion, we demonstrate that EMMPRIN activation in ALS occurs also in astrocytes where it exacerbates their pathological phenotype possibly contributing to the progression of the disease. Furthermore, we suggest the potential use of an anti-EMMPRIN antibody to reduce astrocytic activation during the disease.
The glare illusion in individuals with schizophrenia
Authors: Tamura Hideki , Hoshino Aiko 
Published: February 2025

AbstractIndividuals with schizophrenia are known to demonstrate unique reactions to visual illusions, and prior research has indicated a potential link between their increased susceptibility to geometric illusions and specific symptom profiles. While various illusory experiences have been examined among individuals with schizophrenia, their responses to brightness-related illusions remain poorly understood. In this study, we investigated how individuals with schizophrenia perceive the glare illusion, in which the apparent brightness of the central region is increased. A total of 30 patients with schizophrenia and 34 control participants were recruited. During each trial, a glare or control image (standard stimulus) was presented alongside a control image (comparison stimulus) with one of seven luminance levels. In the glare condition, the standard stimulus was a glare image; in the control condition, two control images were presented, but only the luminance of the comparison stimulus varied. The participants were asked to judge which central region appeared brighter. The results revealed that the individuals with schizophrenia exhibited greater susceptibility to the glare illusion than did the control participants. However, no significant associations were found between susceptibility to the glare illusion and scores assessing symptom severity. These findings suggest that differences in visual processing in patients with schizophrenia may increase their susceptibility to brightness illusions, although this phenomenon is independent of symptom characteristics. Understanding these perceptual alterations may aid in the development of objective measures of visual cognition for patients with schizophrenia.
Bacterial sexually transmitted infections and related antibiotic use among individuals eligible for doxycycline post-exposure prophylaxis in the United States
Authors: Parker Anna M. , Chang Jennifer J. , Chen Ligong , King Laura M. , McCoy Sandra I. , Lewnard Joseph A. , Bruxvoort Katia J. 
Published: February 2025

ABSTRACTBackgroundDoxycycline postexposure prophylaxis (doxyPEP) can prevent bacterial sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women. However, concern surrounds the volume of tetracycline use needed to realize these benefits, and whether potential risks of increased tetracycline exposure outweigh benefits of doxyPEP for specific populations.MethodsWe estimated incidence rates of gonorrhea, chlamydia, and syphilis and related antibiotic prescribing among commercially-insured US males and transgender individuals using the Merative MarketScan® Research Databases during 2016-2019. We evaluated potential impacts of doxyPEP implementation under risk-based prioritization schemes focusing on HIV pre-exposure prophylaxis (PrEP) recipients, people living with HIV (PLWH), and people with prior STI diagnoses.ResultsIncidence rates of gonorrhea, chlamydia, and syphilis among PLWH and PrEP recipients with ≥1 STI diagnosis in the prior year totaled 33.3-35.5 episodes per 100 person-years. Direct effects of doxyPEP could prevent 7.4-9.6 gonorrhea diagnoses, 7.3-8.1 chlamydia diagnoses, and 3.1-5.9 syphilis diagnoses per 100 person-years within these populations. Expected increases in tetracycline consumption resulting from doxyPEP implementation were equivalent to 271.9-312.9 additional 7-day doxycycline treatment courses (resembling current standards for chlamydia treatment) per 100 person-years of use. This increase corresponded to the equivalent of 36.5-37.0, 37.0-38.7, and 46.1-100.2 additional 7-day doxycycline treatment courses for each prevented chlamydia, gonorrhea, and syphilis episode, respectively. These increases in doxycycline use exceeded anticipated reductions in STI-related prescribing of cephalosporins, macrolides, and penicillins by 16-69 fold margins.ConclusionsEstimates of changes in antibiotic use and STI incidence resulting from doxyPEP implementation in differing populations may inform priority-setting for this intervention.
Routine immunization intensification, vaccination campaigns, and measles transmission in Southern Nigeria
Authors: Thakkar Niket , Oteri Avuwa Joseph , McCarthy Kevin 
Published: February 2025

AbstractIn this paper, we compare – in terms of their estimated effects on disease transmission – Southern Nigeria’s large-scale measles vaccination campaigns since 2010 to a unique, more targeted routine immunization intensification that happened in 2019. A main focus of the discussion throughout is that quantifying intervention impact in real epidemiologies requires us to disentangle competing, dynamic sources of immunity, including unreported infection. To address this inference challenge, we create a collection of state-level, stochastic transmission models capable of estimating underlying measles susceptibility based on surveillance and survey data. Leveraging these models, we find that the 2019 intensification, despite being restricted in scale to children under 2 years-old, had an effect on transmission comparable to the region’s larger vaccination campaigns targeting children up to 5. This implies that vaccines delivered in that effort were more than twice as likely to reach a susceptible child.
Transfer of Learned Object Manipulations between Two- and Five-Digit Grasps
Authors: Ulloa-Marquez Jordana , Gutterman Jennifer , Santello Marco , Gordon Andrew M. 
Published: February 2025

ABSTRACTSuccessful object manipulation involves integrating object properties into a motor plan and scaling fingertip forces through learning. This study investigated whether learned manipulations using a two-digit grip transfer to a five-digit grip and vice versa, focusing on the challenges posed by added degrees of freedom in force distribution. The goal of the task was to exert the necessary compensatory torque (Tcom) and vertical forces to minimize object roll on a visually symmetrical object that with an asymmetrical mass distribution. To examine this, subjects performed blocked consecutive learning trials before switching grip type. Our results support the learning transfer between two-digits and five-digit grasp configurations despite challenges in maintaining perfect stability during the grip switch. Subjects adapted their grip forces (GF), center of pressure (CoP), and Tcom to minimize object roll, with significant improvements observed from novel (1st) to transfer (11th) trials. These findings suggest high-level, effector-independent representations of object manipulation that enable generalization across grip types, though some limitations in force distribution and digit position arise during transfers.
Efficient elastic tissue motions indicate general motor skill
Authors: Namburi Praneeth , Pallarès-López Roger , Folgado Duarte , Magana-Salgado Uriel , Ryu Enya , Kappacher Armin , Gamboa Hugo , Anthony Brian W. , Daniel Luca 
Published: February 2025

AbstractInsights into the general nature of motor skill could fundamentally change how we develop movement abilities, like how education develops thought. This would have far-reaching implications for enhancing musculoskeletal well-being and performance, reducing musculoskeletal injury risk, and promoting graceful ageing. Here, we sought to identify indicators of general motor skill–those shared by experts across disciplines (e.g., squash, ballet, volleyball, hip-hop) during non-specialized movements (e.g., reaching for water). Identifying such general indicators of motor skill has remained elusive. Using ultrasound imaging with deep learning and optical flow analysis, we tracked elastic tissues (muscles and associated connective tissues) during a simple reaching task performed similarly by world-class athletes and regional-level athletes drawn from diverse disciplines, as well as untrained non-experts. We analyzed previously unexamined inefficiencies: transverse elastic tissue motions orthogonal to muscle fiber direction and physiological tremors, which are oscillations that do not contribute to the net work done by muscles. We discovered that world-class experts minimize both these inefficient motions compared to regional level athletes and non-experts. While regional-level athletes surprisingly showed similar inefficiencies to non-experts, they used elastic tissues more effectively, achieving equivalent movements with smaller actuation-related tissue motions. We establish elastic tissue motion as a key indicator of general motor skill, expanding our understanding of elastic mechanisms and their role in general aspects of motor skill.
Astrocytic MAOB-GABA axis as a molecular brake on repair following spinal cord injury
Authors: Lee Hye Yeong , Lee Jung Moo , Lee Hye-Lan , Park Jiyeon , An Heeyoung , Park Eun Kyung , Hwang Sae Yeon , Hwang Gwang Yong , Kim Keung Nyun , Nam Min-Ho , Lee Seung Eun , Kang Hyunji , Won Joungha , Jang Bo Ko , Lee Elijah Hwejin , Choi SunYeong , Park Mingu Gordon , Kim Sang Wook , Park Ki Duk , Lee SeungHwan , Lee C. Justin , Ha Yoon 
Published: February 2025

ABSTRACTNeuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system (CNS) injury. The glial scar has been proposed as a major contributor to this failure in the regenerative process. However, its underlying molecular and cellular mechanisms remain unclear. Here, we report that monoamine oxidase B (MAOB)-dependent excessive GABA release from reactive astrocytes suppresses CNS repair system by reducing BDNF and TrkB expression in severe spinal cord injury (SCI) animal models. Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery. Notably, the selective MAOB inhibitor, KDS2010, facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model. Its dose-dependent effects were further validated in a monkey SCI model. Moreover, KDS2010 demonstrates a tolerable safety profile and dose-proportional pharmacokinetics in healthy humans during a phase 1 clinical trial. Our findings identify the astrocytic MAOB-GABA axis as a crucial molecular and cellular brake on CNS repair system following SCI and highlight translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.
The 16p11.2 microdeletion influences how early-life microbiota perturbations affect hippocampal development and behavior throughout the lifespan
Authors: McDermott Courtney R. , Gao Zhan , Mirmajlesi Anya S. , Ntim Christiana , Kimbark Katherine , Thomas Divya , Mughal Zain , Zhang Xue-Song , Zhou Xiaofeng , Popov Daniel , Halchenko Alisa , Xing Jinchuan , Thakker-Varia Smita , Alder Janet , Millonig James H. , Samuels Benjamin A. , Blaser Martin J. , DiCicco-Bloom Emanuel 
Published: February 2025

AbstractNeurodevelopmental disorders result from interactions between genetic predisposition and environmental risk factors, with infancy being the most vulnerable period. We designed a longitudinal study to determine how short-term antibiotic exposure during early postnatal life impacts the gut microbiome, neurodevelopment, and behavior, and whether these alterations were exacerbated by the neurodevelopmental disorder-associated 16p11.2 microdeletion (16pDel) mutation. The cephalosporin antibiotic, cefdinir, broadly altered the gut microbiome acutely, with persistent reductions in severalLachnospiraceaegenera despite overall recovery. These alterations preceded long-term behavioral changes, including reduced juvenile sociability, compromised risk assessment, and deficits in associative learning. Remarkably, only cefdinir-exposed 16pDel mice had changes in hippocampal stem cell proliferation, subsequent adolescent cell numbers, and gene expression compared to other groups, demonstrating that genetic predisposition can modulate the effects of early-life antibiotic exposure on neurodevelopment. These alterations may be mediated by gastrointestinal disturbances, as cefdinir-exposed 16pDel males had increased intestinal permeability and shifted metabolite profiles including arginine biosynthesis and glycerophospholipid metabolism. Taken together, this study highlights how early-life microbial alterations affect behavior and reveals that genetic predisposition influences antibiotic-induced changes in hippocampal development. Further, these insights identify metabolic mechanisms as potential targets for intervention and may raise concerns regarding antibiotic use during infancy.
The genetic basis for synchronised time perception in plant populations
Authors: Lock Sarah C. L. , McCarthy Kayla , Ronald James , Anwer Muhammad Usman , Davis Amanda M. , Hallstein Marc , Redmond Ethan J. , Knight Marina , Davis Seth J. , Ezer Daphne 
Published: February 2025

AbstractSynchronised developmental timing is important for ensuring crop uniformity and high yields. However, climate change is leading to crops being grown at different latitudes, varying their exposures to photoperiods over seasons and impacting developmental timings. We investigated whether the response of circadian rhythms in seedlings to changes in photoperiod would enable us to predict the timing and synchronization of flowering. Indeed, we show that the same Quantitative Trait Loci (QTLs) are associated to circadian traits in seedlings and developmental traits during bolting, using the first recombinant inbred lines (RILs) between African and European Arabidopsis lineages, spanning diverse latitudes. Two QTLs contain K-Homology Domain RNA binding proteins (KH17, KH29) and are associated with splicing variants in known flowering genes, MADS AFFECTING FLOWERING2 and 3 (MAF2, MAF3), including generating chimeric transcripts, a potential mechanism for accelerated proteome evolution. Natural variants in KH17, including in its prion-like domain, are associated with de-coupling the mean and synchronization of flowering time, enabling greater adaptation of population-level heterogeneity in developmental timings. Our results suggest that circadian traits in seedlings could be used to screen for agriculturally relevant developmental traits in mature plants, enabling efficient breeding of climate-resilient crops.
Exploring Hippocampal Vulnerability: Diminished Angiogenic Capacity in the Hippocampus Compared to the Cortex
Authors: Li Xiaojie , Li Nanjing , He Yao , Zhong Qixing , Zhong Zhihui 
Published: February 2025

AbstractBackgroundThe hippocampus is one of the first regions affected in various neurodegenerative diseases. In this study, investigated the vascular factors contributing to its susceptibility, aiming to elucidate the underlying vascular mechanisms.MethodUtilizing publicly available single-cell databases, we analyzed the differential expression of genes in blood-brain barrier (BBB)-associated cells within the hippocampus and compared them to those in the cortex. Those genes were further validated in mouse and ischemia rat models.ResultsWe identified differentially expressed genes (DEGs) in endothelial cells, pericytes, and astrocytes in the BBB. Subsequent gene ontology (GO) enrichment analysis and protein-protein interaction (PPI) network analysis identified key hub genes:Kdr,Fn1,Pecam1,Cd34, andCd93,that related to angiogenesis. They differential expression was then experimentally verified using micro-vessels from mouse and rat brains: In the rat ischemia model, we observed up-regulation of angiogenesis-related genes, includingKdr,Cd34, andCd93, in the microvasculature of both the hippocampus and cortex, with relatively lower expression in the hippocampus.ConclusionThese findings suggest that the hippocampus has a reduced angiogenic capacity compared to the cortex, which may contribute to its increased vulnerability to neurological disorders.