bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating HiTOP and RDoC Frameworks Part II: Shared and Distinct Biological Mechanisms of Externalizing and Internalizing Psychopathology
Authors: Davis Christal N. , Khan Yousef , Toikumo Sylvanus , Jinwala Zeal , Boomsma Dorret I. , Levey Daniel F. , Gelernter Joel , Kember Rachel L. , Kranzler Henry R. 
Published: February 2025

AbstractBackgroundThe Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic and mechanistic aspects of psychopathology, respectively. We used a multi-omics approach to examine how externalizing (EXT), internalizing (INT), and shared EXT+INT liability map onto these models.MethodsWe conducted analyses across five RDoC units of analysis: genes, molecules, cells, circuits, and physiology. Using genome-wide association studies from the companion Part I article, we identified genes and tissue-specific expression patterns. We used drug repurposing analyses that integrate gene annotations to identify potential therapeutic targets and single-cell RNA sequencing data to implicate brain cell types. We then used magnetic resonance imaging data to examine brain regions and circuits associated with each psychopathology spectrum. Finally, we tested causal relationships between each spectrum and physical health conditions.ResultsUsing five gene identification methods, EXT was associated with 1,759 genes, INT with 454 genes, and EXT+INT with 1,138 genes. Drug repurposing analyses identified potential therapeutic targets, including those that affect dopamine and serotonin pathways. Expression of EXT genes was enriched in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT+INT liability was associated with reduced gray matter volume in the amygdala and subcallosal cortex. Using Mendelian randomization, INT showed stronger causal effects on physical health—including chronic pain and cardiovascular diseases—than EXT.ConclusionsOur findings revealed shared and distinct pathways underlying psychopathology. Integrating genomic insights with the RDoC and HiTOP frameworks advanced our understanding of mechanisms that underlie EXT and INT psychopathology.
Enhancing Diagnostic Precision in Thyroid Nodule Classification: A Deep Learning Approach to Automated Ultrasound Image Analysis
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Gabriela Correia , Nunes Carneiro Andrade João Cláudio , Vinhaes Bittencourt Alcina Maria , de Figueiredo Adriana Malta , de Oliveira Luís Matos 
Published: February 2025

ABSTRACTIntroductionEscalating thyroid nodule prevalence necessitates precise ultrasonographic diagnosis, which is constrained by operator-dependent variability. Convolutional neural network (CNN)-based artificial intelligence (AI)/machine learning (ML) frameworks can improve segmentation, malignancy prediction, and interobserver concordance, yet they often lack real-world clinical validation, interpretable architectures, and actionable validation frameworks for translational integration.ObjectiveTo improve diagnostic accuracy in thyroid nodule classification using a deep learning (DL) approach for automated analysis of ultrasound images.MethodThis methodology employed a multicenter, retrospective cohort of anonymized thyroid ultrasound images (benign/malignant, histopathology-confirmed) sourced from PubMed®. Images were preprocessed (normalization, denoising) with expert-annotated regions of interest (ROIs). A CNN-based DL framework (ResNet-50, EfficientNet-B0) was fine-tuned via transfer learning for automated nodule detection, segmentation, and malignancy classification aligned with ACR TI-RADS™ criteria. Validation utilized an independent test set, diagnostic metrics (sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC)), and interobserver analysis (Cohen’s kappa) against three sonographers. Statistical rigor included PSPP-driven paired t-tests, chi-square tests, and McNemar’s tests to quantify AI-human concordance and optimize ACR TI-RADS™ integration for risk stratification.ResultsThe AI model demonstrated high diagnostic efficacy: sensitivity 92.5%, specificity 88.3%, accuracy 90.4%, and AUC-ROC 0.94, surpassing sonographers in both sensitivity (p<0.001) and specificity (p<0.01). Interobserver concordance (Cohen’s κ=0.89) exceeded human variability (κ=0.72–0.85). ACR TI-RADS™ integration achieved 91.2% agreement, enhancing objectivity in the assessment of intermediate-risk nodules (categories 3–4). Feature analysis highlighted robust detection of hypoechoic patterns (94.2% sensitivity) and irregular margins (91.8% sensitivity), aligning with ACR TI-RADS™ criteria and confirming the AI’s potential to standardize risk stratification and reduce diagnostic subjectivity.ConclusionAdvanced AI enhances thyroid ultrasound diagnostics through precise nodule detection and classification, reduced interobserver variability, and ACR TI-RADS™-aligned feature extraction, thereby boosting diagnostic confidence and clinical decision-making.
Protein Synthesis Blockade Prevents Fear Memory Reactivation via Inhibition of Engram Synapse Strengthening
Authors: Hong Ilgang , Kim Yeonjun , Jung Hyunsu , Kim Chang-Ho , Cho Jun-Hyeong , Kaang Bong-Kiun 
Published: February 2025

AbstractMemory relies on ensembles of engram cells in the brain. While previous studies have established the existence of these cells, the relationship between cellular and synaptic activity remains unclear. To address this, we applied the dual e-GRASP technique in mice to examine synaptic connectivity between the ventral CA1 and the basal amygdala during memory formation. We found that contextual fear conditioning increased engram-to-engram synapse (engram synapse) density and induced structural potentiation, underscoring their importance in associative memory. Additionally, we investigated the role of protein synthesis in memory formation by inducing retrograde amnesia using anisomycin, a protein synthesis inhibitor. Mice injected with anisomycin once (1xANI) showed impaired natural recall but still displayed fear responses upon optogenetic reactivation of engram cells. In contrast, mice that received four anisomycin injections over six hours (4xANI) showed significantly impaired natural recall and failed to exhibit fear responses upon optogenetic reactivation. This behavioural phenotype was correlated with synaptic changes: 1xANI mice exhibited no significant reduction in engram synapse density but had significantly smaller spine sizes, whereas 4xANI mice showed both a significant reduction in engram synapse density and spine size. Our results indicate that protein synthesis inhibition significantly reduces engram synapse density and spine size, changes that correlate with reductions in fear memory during both natural recall and artificial reactivation.
Genomic Insights into the Demographic History and Local Adaptation of Wild Boars Across Eurasia
Authors: Wang Zishuai , Li Zixin , Huang Tao , Chen Jianhai , Xu Pan , Qiao Ruimin , Yin Hongwei , Song Chengyi , Zhang Dongjie , Liu Di , Zhao Shuhong , Groenen Martien A. M. , Madsen Ole , Zhang Yanlin , Bai Lijing , Li Kui 
Published: February 2025

AbstractWild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Its expansion across Eurasia, especially in central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split ∼3.6 Mya, with Central Asian and Southern Chinese ancestors diverging ∼1.8 Mya. The split between Central Asian and European-Near East ancestors occurred ∼0.9 Mya, followed by a European-Near East divergence ∼0.6 Mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants inLPIN1, associated with cold adaptation, and a missense mutation inALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation, and shed light on domestic pigs breeding.
Network Biomarkers of Alzheimer’s Disease Risk Derived from Joint Volume and Texture Covariance Patterns in Mouse Models
Authors: Bridgeford Eric W. , Chung Jaewon , Anderson Robert J. , Mahzarnia Ali , Stout Jacques A. , Moon Hae Sol , Han Zay Yar , Vogelstein Joshua T. , Badea Alexandra 
Published: February 2025

AbstractAlzheimer’s disease (AD) lacks effective cures and is typically detected after substantial pathological changes have occurred, making intervention challenging. Early detection and understanding of risk factors and their downstream effects are therefore crucial. Animal models provide valuable tools to study these prodromal stages. We investigated various levels of genetic risk for AD using mice expressing the three major human APOE alleles in place of mouse APOE. We leverage these mouse models utilizing high-resolution magnetic resonance diffusion imaging, due to its ability to provide multiple parameters that can be analysed jointly. We examine how APOE genotype interacts with age, sex, diet, and immunity to yield jointly discernable changes in regional brain volume and fractional anisotropy, a sensitive metric for brain water diffusion. Our results demonstrate that genotype strongly influences the caudate putamen, pons, cingulate cortex, and cerebellum, while sex affects the amygdala and piriform cortex bilaterally. Immune status impacts numerous regions, including the parietal association cortices, thalamus, auditory cortex, V1, and bilateral dentate cerebellar nuclei. Risk factor interactions particularly affect the amygdala, thalamus, and pons. APOE2 mice on a regular diet exhibited the fewest temporal changes, suggesting resilience, while APOE3 mice showed minimal effects from a high-fat diet (HFD). HFD amplified aging effects across multiple brain regions. The interaction of AD risk factors, including diet, revealed significant changes in the periaqueductal gray, pons, amygdala, inferior colliculus, M1, and ventral orbital cortex. Future studies should investigate the mechanisms underlying these coordinated changes in volume and texture, potentially by examining network similarities in gene expression and metabolism, and their relationship to structural pathways involved in neurodegenerative disease progression.
Machine Learning Reveals Immediate Disruption in Mosquito Flight when exposed to Olyset Nets
Authors: Qureshi Yasser M. , Voloshin Vitaly , Guy Amy , Ranson Hilary , McCall Philip J. , Towers Cathy E. , Covington James A. , Towers David P. 
Published: February 2025

AbstractInsecticide-treated nets (ITNs) remain a critical intervention in controlling malaria transmission, yet the behavioural adaptations of mosquitoes in response to these interventions are not fully understood. This study examined the flight behaviour of insecticide-resistant (IR) and insecticide-susceptible (IS) Anopheles gambiae strains around an Olyset net (OL), a permethrin-impregnated ITN, versus an untreated net (UT). Using machine learning (ML) models, we classified mosquito flight trajectories with high accuracy (0.838) and ROC AUC (0.925). Contrary to assumptions that behavioural changes at OL would intensify over time, our findings show an immediate onset of convoluted, erratic flight paths for both IR and IS mosquitoes around the treated net. SHAP analysis identified three key predictive features of OL exposure: frequency of zero-crossings in flight angle change, first quartile of flight angle change, and zero-crossings in horizontal velocity. These suggest disruptive flight patterns, indicating insecticidal irritancy. While IS mosquitoes displayed rapid, disordered trajectories and mostly died within 30 minutes, IR mosquitoes persisted throughout the 2-hour experiments but exhibited similarly disturbed behaviour, suggesting resistance does not fully mitigate disruption. Our findings challenge literature suggesting permethrin’s repellency in solution form, instead supporting an irritant or contactdriven effect when incorporated into net fibres. This study highlights the value of ML-based trajectory analysis for understanding mosquito behaviour, refining ITN configurations and evaluating novel active ingredients aimed at disrupting mosquito flight behaviour. Future work should extend these methods to other ITNs to further illuminate the complex interplay between mosquito behaviour and insecticidal intervention.
Disease as a mediator of somatic mutation – life history coevolution
Authors: Hochberg Michael E. 
Published: February 2025

AbstractMulticellular organisms are confronted not only with mutation in germline, but also mutations emerging in somatic cells. Somatic mutations can lead cancers and possibly contribute to aging phenotypes. Prevailing wisdom suggests somatic mutations are limited by evolved defences, either targeting DNA or post-mutational cellular states. Here, I analyse simple models for metazoans and humans in particular, incorporating the possibility that mutation rate trades-off of organism longevity, defined as the age at which natural selection becomes negligible. The models assume selection acts to reduce mutation rate and prevent disease, both of which contribute to selecting for longer lifespan. We detail equilibrium conditions and find coevolutionary oscillations under certain parameter combinations. Notably, disease prevention can lead to mutational tolerance and this can contribute to explaining empirical cross-species patterns in longevity vs. mutation rate. We conclude that mutational disease and cancer in particular have required characteristics to be mediators of mutation rate – lifespan coevolution. The mutational tolerance that results from this coevolution can contribute to explaining the incidences of other diseases and conditions, including aging.
Background color matching influences sexual behavior, growth, and mortality rate in an African cichlid fish
Authors: Moore Travis I. , Bright William G. , Bell William E. , Solomon-Lane Tessa K. , Alvarado Sebastian G. , Dijkstra Peter D. 
Published: February 2025

AbstractPhenotypic plasticity allows organisms to adapt to changing environments within their lifetimes. The cost of plastic adaptations may constrain the persistence of plasticity over evolutionary time. One potential cost is the possibility that phenotypic adjustment to specific environments can cause correlated responses that are not necessarily adaptive. Males in the African cichlidAstatotilapia burtoniare blue or yellow, and males are able adjust their body coloration to the color of the background, presumably to increase crypsis. To test whether background color influences fitness-related traits, we raised mix-sex groups of juvenileA. burtonito adulthood in yellow or blue tanks. We found that fish in blue tanks were darker and more bluish, whereas fish reared in yellow tanks were paler and more yellow in body coloration. Males, but not females, from blue tanks showed earlier sexual maturation than those held in yellow tanks. However, across the duration of the experiment, there was a higher frequency of females mouthbrooding in groups housed in yellow tanks than those that were housed in blue tanks. In addition, fish in blue tanks exhibited reduced growth rate but higher survivorship relative to their yellow-reared counterparts. Our data suggests that background color affects important fitness-related traits in a color polymorphic cichlid, which may influence the evolution of phenotypic plasticity.
Olfactory preferences and chemical differences of fruit scents forAedes aegyptimosquitoes
Authors: Leon-Noreña Melissa , Tauxe Genevieve M. , Riffell Jeffrey A. 
Published: February 2025

AbstractFeeding on the sugar of fruits and flowers is vital for mosquitoes and increases their lifespan, reproduction, and flight activity. Olfaction is a key sensory modality in mediating mosquito responses to sugar sources. Previous studies have demonstrated that natural nectar sources from fruits and flowers can vary in attractiveness to mosquitoes, with some sources preferred over others. However, how the attractiveness of different fruits relates to the chemical composition of their scent and the responses they evoke from the mosquito’s peripheral olfactory system, is still not understood. In this study, we use closely related fruit species and their varieties to examine how changes in scent chemistry can influence the fruit’s attractiveness toAedes aegyptimosquitoes and examine how the mosquito’s olfactory responses (via electroantennogram recordings, or EAG) correlate with those differences. Our results show that mosquitoes are attracted to the scents of certain fruits (Mangifera indica, Prunus perspica, Psidium guajava, Musa acuminata), whereas others (Pyrus communis, Citrus limon) elicited responses not significantly different from the negative control. Chemical analyses of the scents showed that attractive fruits have distinct chemical profiles, and amongst closely related fruits, minor changes in the relative proportions of scent compounds can modify the attractiveness. These minor differences in the fruit scent were not reflected in the EAG responses, which showed similar responses to scents from different fruit species and closely related varieties. Experimentally altering the chemical proportion of a single compound in attractive scents caused a significant decrease in attraction to levels similar to the less attractive cultivars. Our results demonstrate that mosquitoes are sensitive to compound proportions in attractive odors, which have implications for the olfactory processing of complex odor sources, like those from plants or blood hosts.Summary StatementAedes aegyptimosquitoes show specific and selective fruit scent preferences related to differences in the proportion of compounds in the scent.
Effects of GlobalRipk2Genetic Deficiency in Aged Mice following Experimental Ischemic Stroke
Authors: Howell John Aaron , Larochelle Jonathan , Gunraj Rachel E. , Stansbury Sofia M. , Liu Lei , Yang Changjun , Candelario-Jalil Eduardo 
Published: February 2025

AbstractBesides the loss of blood and oxygen reaching the ischemic tissue, many secondary effects of ischemic stroke can cause additional tissue death, including inflammation, oxidative stress, and proteomic disturbances. Receptor-interacting serine/threonine kinase 2 (RIPK2) is an important mediator in the post-stroke inflammatory cascade that responds to signals and molecular patterns released by dead or dying cells in the ischemic area. We hypothesize that RIPK2 signaling worsens injury and neurological recovery post-stroke and that global deletion ofRipk2will be protective following ischemic stroke in aged mice. Aged (18-24 months) male mice were subjected to permanent middle cerebral artery occlusion (pMCAO). Vertical grid, weight grip, and open field were conducted at baseline and on days 1, 2, 3, 8, 15, and 22 post-stroke. Cognitive tests (novel object recognition and Y-maze) were performed at baseline and day 28 post-stroke. Infarct size was measured using cresyl violet staining, and reactive gliosis was measured using Iba1 and GFAP staining at day 28 post-stroke. Global deletion ofRipk2(Ripk2-/-) in aged mice resulted in smaller infarct volume and improved performance on vertical grid and weight grip tests compared to aged wildtype (WT) mice. Additionally, agedRipk2-/-mice had less Iba1 staining in the ipsilateral cortex than the aged WT control mice. This study further elucidates the role of RIPK2 signaling in the ischemic cascade and expands our knowledge of RIPK2 in stroke to aged mice. These results support the hypothesis that RIPK2 signaling worsens injury post-stroke and may be an attractive candidate for therapeutic intervention.
Influence of past climate changes and human-mediated introduction on patterns of genetic diversity distribution of the Papuan nutmeg (Myristica argentea) Warb
Authors: Kusuma Jakty , Milaba Adinda C. , Paramitha Amalia , Malaval Victoria , Sari Mei Nita , Nurhuda Cahya , Couderc Marie , Scarcelli Nora , Watts John , Duminil Jérôme 
Published: February 2025

ABSTRACTUnderstanding the distribution of genetic diversity of endemic food tree species holds significant importance for conservation planning and the formulation of effective management strategies. Natural and anthropogenic factors can influence species’ geographic range and distribution of genetic diversity. Here, we tested the relative influence of barriers to gene flow (rivers, mountains and past climate change) and recent human activities on the evolutionary history of an endemic species from Fakfak district, Papua Island,Myristica argenteaWarb (Myristicaceae), better known as Papuan nutmeg.Myristica argenteais a spice tree species used by local populations since centuries/millennia. The species has been introduced in other locations from the region. Fourteen microsatellite markers (nSSRs), whole chloroplast (cp) genome, and nuclear-targeted sequence genes (nrDNA sequence) were used to characterize the genetic diversity, population structure, and demographic history of the species across its distribution range (native and introduced populations). We found that native populations of the species in Fakfak present higher levels of genetic diversity than introduced populations. We further detected the presence of a moderate genetic structure (FST= 0.143), and the presence of three intraspecific genetic clusters. Additionally, our findings indicate that population fragmentation within the native range of the species in Fakfak, may have been influenced by the presence of riparian networks, mountain ranges and by Pleistocene climatic fluctuations. Our results suggest that all introduced populations were sourced mainly from the native population of Raduria, in the South of Fakfak region. Given the population genetic variation across the ranges of Papuan nutmeg, management plans should not treat them as single populations, but rather consider the broader genetic diversity within its range.