bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of protein boosters on antibody responses
Authors: Awakoaiye Bakare , Dangi Tanushree , Penaloza-MacMaster Pablo 
Published: February 2025

AbstractSARS-CoV-2 has infected a large fraction of the human population. Currently, most individuals have developed immunity either through vaccination or natural infection. Despite this, SARS-CoV-2 booster immunizations are still recommended to reduce the risk of reinfections, but there is still limited understanding on how different booster vaccine platforms influence antibody responses. We conducted immunological studies in mice to evaluate the boosting effects of different vaccine platforms on antibody responses. C57BL/6 mice were first primed with an adenovirus serotype 5 (Ad5) vaccine expressing the SARS-CoV-2 spike protein. The mice were then boosted with the same Ad5-based vaccine (homologous boosting) or with a protein-based vaccine (heterologous boosting). Interestingly, the heterologous regimen (Ad5 prime + protein boost) elicited superior antibody responses, relative to the homologous regimen (Ad5 prime + Ad5 boost). Similar potentiation of antibody responses was reported when mice were primed with poxvirus or rhabdovirus vectors and then boosted with protein. These findings highlight a potential advantage of protein booster immunizations to potentiate humoral immunity.
Effect of upper limb isometric training (ULIT) on hamstring strength in early postoperative anterior cruciate ligament reconstruction patients: study protocol for a randomized controlled trial
Authors: Muhamad Hendri Efri Noor , A Hamid Mohamad Shariff , Md Yusoff Badrul Akmal Hisham , Mohamad Norlelawati , Yusof Ashril 
Published: February 2025

AbstractAnterior cruciate ligament (ACL) injuries impact approximately 68.6 per 100,000 individuals annually, with ACL reconstruction (ACLR) being a common intervention for restoring knee stability in physically active individuals. Despite advancements in surgical techniques and rehabilitation protocols, patients often experience prolonged recovery, hamstring weakness, and neuromuscular deficits, increasing the risk of re-injury and osteoarthritis. Early-phase ACLR rehabilitation primarily focuses on managing pain, swelling, and quadriceps strength, frequently neglecting the critical role of hamstrings in knee stabilization. This leaves a gap in addressing imbalances that hinder functional recovery and return-to-sport timelines.Upper limb isometric training (ULIT) presents an innovative approach to enhance hamstring activation during the early rehabilitation phase. By leveraging the posterior myofascial kinetic chain (PMKC), ULIT indirectly stimulates hamstrings through bilateral static upper limb exercises, such as wall push up, shoulder extension and scapular retraction, promoting neuromuscular coordination and kinetic chain synergy. These exercises mitigate challenges associated with direct hamstring loading, such as arthrogenic muscle inhibition and graft protection needs.Preliminary research suggests upper limb resistance exercise at submaximal voluntary contraction facilitates inter-limb strength gains, improves core abdominals and hamstring activation, and reduces knee imbalances, supporting accelerated recovery and reduced re-injury risk. The ULIT demonstrates potential as an alternative warm-up exercise to promote hamstring activation and enhance overall readiness for physical activity. Emerging findings highlight ULIT as a safe and potentially effective supplementary intervention, but further research is essential to establish its role in ACLR rehabilitation and develop evidence-based protocols.This study aims to evaluate the effects of integrating ULIT into standard care rehabilitation on hamstring strength and physical function in early-phase postoperative ACLR patients with hamstring autograft. The findings could introduce a novel and effective strategy to optimize recovery, enhance functional outcomes, and support a safer return to sport.Trial registration numberACTRN12624001445561 and available athttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388441&isReview=true.
Predicting Mutation-Induced Relative Protein-Ligand Binding Affinity Changes via Conformational Sampling and Diversity Integration with Subsampled Alphafold2 in Few-Shot Learning
Authors: Xie Liangxu , Lu Xiaohua , Zhang Dawei , Xu Lei , Yang Mingjun , Jeong Young-Seob , Chang Shan , Xu Xiaojun 
Published: February 2025

AbstractPredicting the impact of mutations on protein-ligand binding affinity is crucial in drug discovery, particularly in addressing drug resistance and repurposing existing drugs. Current structure-based methods, including deep learning and physics-based computational techniques, are constrained by their dependence on known protein-ligand complex structures. The lack of structural data for mutated proteins, coupled with the potential for mutations to alter protein conformational states, poses challenges for reliable predictions. To address the challenge, we propose a few-shot learning approach that integrates AlphaFold2 subsampling, ensemble docking, and Siamese learning to predict the relative binding affinity changes induced by mutations. We benchmark our approach for predicting binding affinity changes in 31 variants of the mutated Abelson tyrosine kinase (ABL). The conformation ensembles for each ABL variant are generated using AlphaFold2 subsampling. Subsequently, the most likely conformational states are selected through Gaussian fitting to construct the pairwise structural inputs and compute relative binding energies. To leverage the structural information, we utilize the multimodal inputs including contact maps and molecular graphs as the molecular representation in the Siamese learning network. The relative binding affinities are derived by averaging the values predicted by the Siamese learning model across the constructed conformational pairs. Benchmarking on the Tyrosine kinase inhibitors (TKI) dataset and the direct binding affinity using the refined set of PDBbind database, our proposed approach achieves increased prediction accuracy in estimating relative binding affinities by using the conformations generated from AlphaFold2 subsampling, which includes structural diversity in the prediction and avoids reliance on crystal structures. We anticipate the approach will be valuable for predicting binding energy changes induced by mutations in proteins or ligands, facilitating drug discovery efforts.
The sensorimotor basis of subjective experience in social synchronization behavior
Authors: Bremer Jan P. , Knorr Marius S. , Göschl Florian , Maye Alexander , Engel Andreas K. , Schneider Till R. 
Published: February 2025

1.AbstractThe sensorimotor contingency (SMC) theory addresses action and perception as constitutive factors to one another – what is being perceived depends on what we do and vice versa. Accordingly, perception is seen as an active process of probing the environment and receiving feedback from it. These action-effect patterns may also be a predominant factor in social interactions. They can manifest in the phenomenon of synchronization, for example, when applause, gait, or posture in conversations synchronize unintentionally and form the basis of the concept of socially deployed sensorimotor contingencies (socSMCs). In this study, we introduce and compare measures used to study complex systems in order to quantify the information-theoretic basis of socSMCs. Two human participants had to synchronize arm movements in a full body virtual reality (VR) environment with each other. We aimed to evaluate the information-theoretic measures transfer entropy and mutual information in this complex motion synchronization task. Furthermore, in our experiment participants shared a mutual sensation of synchronicity and creativity for their interaction solely based on their movements. These subjective ratings of synchronicity and creativity can be predicted using transfer entropy and mutual information, showing that informational coupling between agents is relevant to subjective experience of interaction as described by the concept of socSMCs.
Altered Functional Network Energy Across Multiscale Brain Networks in Preterm vs. Full-Term Subjects: Insights from the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Li Qiang , Jensen Dawn , Fu Zening , Jakim Teddy , Seraji Masoud , Süleymanoğlu Selim , Bharadwaj G. Hari Surya , Chen Jiayu , Calhoun Vince D. , Liu Jingyu 
Published: February 2025

AbstractInfants born prematurely, or preterm, can experience altered brain connectivity, due in part to incomplete brain development at the time of parturition. Research has also shown structural and functional differences in the brain that persist in these individuals as they enter adolescence when compared to peers who were fully mature at birth. In this study, we examined functional network energy across multiscale functional connectivity in approximately 4600 adolescents from the Adolescent Brain Cognitive Development (ABCD) study who were either preterm or full term at birth. We identified three key brain networks that show significant differences in network energy between preterm and full-term subjects. These networks include the visual network (comprising the occipitotemporal and occipital subnetworks), the sensorimotor network, and the high cognitive network (including the temporoparietal and frontal subnetworks). Additionally, it was demonstrated that full-term subjects exhibit greater instability, leading to more dynamic reconfiguration of functional brain information and increased flexibility across the three identified canonical brain networks compared to preterm subjects. In contrast, those born prematurely show more stable networks but less dynamic and flexible organization of functional brain information within these key canonical networks. In summary, measuring multiscale functional network energy offered insights into the stability of canonical brain networks associated with subjects born prematurely. These findings enhance our understanding of how early birth impacts brain development.
SEX-DEPENDENT MODULATION OF BEHAVIORAL ALLOCATION VIA VENTRAL TEGMENTAL AREA-NUCLEUS ACCUMBENS SHELL CIRCUITRY
Authors: McLaurin Kristen A. , Illenberger Jessica M. , Li Hailong , Booze Rosemarie M. , Mactutus Charles F. 
Published: February 2025

ABSTRACTDiagnostic criteria for substance use disorder, cocaine type (i.e., cocaine use disorder), outlined in the 5thedition of theDiagnostic and Statistical Manual,imply that the disorder arises, at least in part, from the maladaptive allocation of behavior to drug use. To date, however, the neural circuits involved in the allocation of behavior have not been systematically evaluated. Herein, a chemogenetics approach (i.e., designer receptors exclusively activated by designer drugs (DREADDs)) was utilized in combination with a concurrent choice self-administration experimental paradigm to evaluate the role of the mesolimbic neurocircuit in the allocation of behavior. Pharmacological activation of hM3D(Gq) DREADDs in neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (AcbSh) induced a sex-dependent shift in the allocation of behavior in rodents transduced with DREADDs. Specifically, male DREADDs animals exhibited a robust increase in responding for a natural (i.e., sucrose) reward following pharmacological activation of the VTA-AcbSh circuit; female DREADDs rodents, in sharp contrast, displayed a prominent decrease in drug-reinforced (i.e., cocaine) responding. The sequential activation of hM3D(Gq) and KORD DREADDs within the same neuronal population validated the role of the VTA-AcbSh circuit in reinforced responding for concurrently available natural and drug rewards. Collectively, the VTA-AcbSh circuit is fundamentally involved in behavioral allocation affording a key target for the development of novel pharmacotherapies.
Proteome-wide Prediction of the Functional Impact of Missense Variants with ProteoCast
Authors: Abakarova Marina , Freiberger Maria Ines , Lierhmann Arnaud , Rera Michael , Laine Elodie 
Published: February 2025

AbstractBackgroundDissecting the functional impact of genetic mutations is essential to advancing our understanding of genotype-phenotype relationships and identifying new therapeutic targets. Despite the progress in sequencing and CRISPR technologies, proteome-wide mutation effect prediction remains challenging. Here, we introduce ProteoCast, a scalable and interpretable computational method for proteome-wide classification of genetic variants and functional protein site identification. It relies solely on evolutionary information, leveraging protein sequence data across organisms.ResultsUsing ProteoCast, we generated mutational landscapes for 22,169Drosophila melanogasterprotein isoforms, categorising over 293 million amino acid substitutions as functionally neutral, uncertain, or impactful. We validated our predictions with over 380 thousand natural polymorphisms observed in the Drosophila Genetic Reference Panel (DGRP) and Drosophila Evolution over Space and Time (DEST) datasets and with FlyBase’s developmentally lethal mutations. About 86% of known lethal mutations were classified as impactful or uncertain, versus only 13% and 18% of DGRP and DEST mutations. Moreover, we performed ProteoCast-guided genome editing experiments, providing a proof-of-concept of the validity of this strategy. Beyond variant effect prediction, ProteoCast detected evolutionary conservation signals in about one-third of 40.5K annotated post-translational modification sites and 83% of ∼90 known short linear motifs. These results support its usefulness for uncovering interaction and regulatory sites in unstructured protein regions.ConclusionsOur results demonstrate ProteoCast applicability for model organisms, contributing to basic genetic research and translational studies. This work provides a publicly available dataset, user-friendly interactive web services, and a locally deployable pipeline tool for further research into gene function and mutation effects in any organism.
Feedback and feedforward control are differentially delayed in cerebellar ataxia
Authors: Cao Di , Wilkinson Michael G.T. , Bastian Amy J. , Cowan Noah J. 
Published: February 2025

1AbstractDamage to the cerebellum can cause ataxia, a condition associated with impaired movement coordination. Typically, coordinated movement relies on a combination of anticipatory mechanisms (specifically, feedforward control) and corrective mechanisms (embodied by feedback control). Here, we show that in 3D reaching in VR, ataxia preserves the visuomotor feedforward and feedback control structure compared to the control group. However, the ataxia group exhibits a small increase in feedback delay (~ 20 ms) and a substantial increase in feedforward delay (~ 70 ms) together with a reduced feedback gain (~25 % lower). Our results suggest that the feedforward and feedback pathways remain largely intact in ataxia, but that time delay deficits and temoral discoordination amongst these control pathways may contribute to the disorder. We also find that providing a preview—analogous to driving on a clear night and seeing the road ahead vs. driving in the fog— improves tracking performance in the ataxia group, although the control group was significantly better able to exploit this preview information. Overall, our results indicate that the feedforward control and preview utilization are relatively well-preserved in individuals with cerebellar ataxia, and that preview could potentially be leveraged to enhance the feedforward performance of those with ataxia.
The use of residual blood specimens in seroprevalence studies for vaccine preventable diseases: A scoping review
Authors: Pilewskie Monica , Prosperi Christine , Bernasconi Abigail , Esteban Ignacio , Niehaus Lori , Ross Connor , Carcelén Andrea C , Moss William J , Winter Amy K 
Published: February 2025

AbstractBackgroundResidual blood specimens offer a cost- and time-efficient alternative for conducting serological surveys. However, their use is often criticized due to potential issues with representativeness of the target population and/or limited availability of associated metadata. We conducted a scoping review to examine where, when, how, and why residual blood specimens have been used in serological surveys for vaccine-preventable diseases (VPDs), and how potential selection biases are addressed.MethodsThe review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We identified relevant papers published between 1999 and 2022 through a literature search of PubMed, Scopus, Embase, Cochrane, and the WHO IRIS database. Study data were captured using Kobo Toolbox, and findings were summarized using descriptive analytical methods.ResultsA total of 601 articles met the inclusion criteria after title, abstract screening, and full-text review. The most commonly studied VPDs using residual blood specimens were COVID-19 (27%), hepatitis E (16%), hepatitis B (10%), influenza (9%), HPV (7%), and measles (7%). Most studies (81%) aimed to estimate population-level seroprevalence. Residual specimens were primarily sourced from patients (55%) or blood donors (36%). Common strategies to address potential biases included comparing results with published estimates (78%) and performing stratified analyses (71%).ConclusionsResidual blood specimens are widely used in seroprevalence studies, particularly during emerging disease outbreaks when rapid estimates are critical. However, the review highlighted inconsistencies in how researchers analyze and report the use of residual specimens. To address these gaps, we propose a set of recommendations to improve the analysis, reporting, and ethical considerations of serological surveys using residual specimens.
SNARE Protein Ykt6 Drives AMPAR Insertion at Synaptic Terminals During LTP
Authors: Takahashi Momoko , Caraveo Gabriela 
Published: February 2025

AbstractYkt6 is a SNARE protein essential for vesicular fusion along the secretory pathway. It has been implicated in α-synuclein (αSyn) pathology and is critically involved in α-synuclein-dependent dementias. αSyn disrupts AMPA receptor (AMPAR) expression at synaptic terminals, which is key for long-term potentiation (LTP)—the cellular basis of memory and learning. AMPAR expression at synaptic terminals relies on the secretory pathway; however, the role of Ykt6 in LTP and its perturbation under αSyn pathological conditions remain unexplored. Here, we demonstrate that Ykt6 is highly expressed in the hippocampus of the mammalian brain, relocalizes to synaptic terminals during LTP, and regulates GluA1 surface expression. Moreover, we found that Ykt6 modulates the synaptic vesicular pools and dendritic arborization. Taken together, our findings establish Ykt6 as an essential SNARE for hippocampal neural function during LTP, with significant implications for α-synuclein-dependent dementias.
Decoding semantics from natural speech using human intracranial EEG
Authors: Pescatore Camille R. C. , Zhang Haoyu , Hadjinicolaou Alex E. , Paulk Angelique C. , Rolston John D. , Richardson R. Mark , Williams Ziv M. , Cai Jing , Cash Sydney S. 
Published: February 2025

AbstractBrain-computer interfaces (BCIs) hold promise for restoring natural language production capabilities in patients with speech impairments, potentially enabling smooth conversation that conveys meaningful information via synthesized words. While considerable progress has been made in decoding phonetic features of speech, our ability to extract lexical semantic information (i.e. the meaning of individual words) from neural activity remains largely unexplored. Moreover, most existing BCI research has relied on controlled experimental paradigms rather than natural conversation, limiting our understanding of semantic decoding in ecological contexts. Here, we investigated the feasibility of decoding lexical semantic information from stereo-electroencephalography (sEEG) recordings in 14 participants during spontaneous conversation. Using multivariate pattern analysis, we were able to decode word level semantic features during language production with an average accuracy of 21% across all participants compared to a chance level of 10%. This semantic decoding remained robust across different semantic representations while maintaining specificity to semantic features. Further, we identified a distributed left-lateralized network spanning precentral gyrus, pars triangularis, and middle temporal cortex, with low-frequency oscillations showing stronger contributions. Together, our results establish the feasibility of extracting word meanings from neural activity during natural speech production and demonstrate the potential for decoding semantic content from unconstrained speech.
Toward passive acoustic occupancy surveys of rare red uakari monkeys (Cacajao ucayalii): using automatic signal recognition and cluster analysis to organize signals?
Authors: Bowler M. , Casinhas I. , Moreno D.Y. , Mori G. , Briceño F. , León J. , Gacheva B 
Published: February 2025

AbstractWe tested a workflow using a cluster analysis to develop a classifier to detect red uakari monkey calls using clustering and Hidden Markov Models, and Kaleidoscope viewer to review and discount false positives. We used recordings collected in a series of behavioral studies on a habituated group of red uakari monkeys on the Yavari-Miri River in the Peruvian Amazon as training data to develop the classifier and tested it on a passive acoustic survey at the same site where uakari distributions were known to us. We estimated detection probabilities for red uakaris and used an occupancy model to estimate habitat use to compare with use determined by behavioral research. We assessed a workflow for processing passive acoustic primate surveys that would eliminate false positives and demand minimal time and coding expertise from those implementing the analyses and reviewing audio recordings. These are key considerations in the design of landscape-scale PAM surveys for rare species.
Post-Synaptic Density Proteins in Oligodendrocytes are Required for Activity-Dependent Myelin Sheath Growth
Authors: Masson MA , Graciarena M , Porte M , Nait Oumesmar B 
Published: February 2025

SUMMARYCompelling evidence demonstrates a functional link between neuronal activity and myelination, highlighting the vital importance of axon-oligodendrocyte crosstalk in myelin physiology and function. However, how neuronal activity is relayed to oligodendroglia to regulate myelin formation remains not fully understood. Here, we aimed to characterize how that myelination is regulated by glutamate vesicular release in zebrafish spinal cord. We compared oligodendrocyte precursor cells (OPCs) and myelinating oligodendrocytes (mOLs) for their close apposition with pre-synaptic boutons and found that these are increased in number on mOLs during myelin internode elongation. Consistently, mOLs show more pre-synaptic boutons during myelin internode elongation compared to OPCs. In addition, we also found that oligodendroglial cells express the post-synaptic density protein 95 (PSD-95) along punctated domains, regardless of their differentiation stage. Genetically targeted PSD-95-GFP expression in oligodendroglia revealed post-synaptic-like domains along their processes and sheaths, which are contacted by axonal pre-synaptic varicosities. These contacts are increased in mOLs. Importantly, CRISPR-Cas9 mediated deletion ofdlg4in oligodendroglia impairs myelin sheath growth, in vivo. Overall, our data indicate that PSD-95 is a key component of axons to oligodendrocytes neurotransmission that regulates myelin sheath growth.HIGHLIGHTSGlutamate vesicular release is required for myelinationAxon-oligodendroglia connectivity increases with oligodendrocyte maturationOligodendrocytes express the post-synaptic density protein 95Dlg4loss-of-function in oligodendroglia impedes myelin sheath growthGRAPHICAL ABSTRACT