bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corticocortical and Corticomuscular Connectivity Dynamics in Standing Posture: Electroencephalography Study
Authors: Fujio Kimiya , Takeda Kenta , Obata Hiroki , Kawashima Noritaka 
Published: May 2024

AbstractCortical involvements, including those in the sensorimotor, frontal, and occipitoparietal regions, are important mechanisms of neural control in human standing. Previous research has shown that cortical activity and corticospinal excitability vary flexibly in response to postural demand. However, it is unclear how corticocortical and corticomuscular connectivity is dynamically modulated during standing balance and over time. This study investigated the dynamics of this connectivity using electroencephalography (EEG) and electromyography (EMG). The EEG and EMG were measured in different 4 positions: sitting (ST), normal quiet standing (QS), one-leg standing (ON), and standing on a piece of wood (WD). For corticomuscular connectivity, we concentrated on sway-varying connectivity in the timing of peak velocity of postural sway in the anteroposterior direction. For the corticocortical connectivity, the time-varying connectivity was quantified, particularly in the θ-band connectivity which is linked to error identification, using a sliding-window approach. The study found that corticomuscular connectivity from the brain to the lower-limb muscle was strengthened during the sway peak in the γ- and β-frequency bands, while the connectivity strength from the muscle to the brain was decreased in the θ- and α-band. For the time-varying connectivity, the θ-connectivity in all time-epoch was divided into 7 states including both posture-relevant and -irrelevant clusters. In one of the 7 states, the strong connectivity pairs were concentrated in the mid-central region and the proportion of epochs from the ON and WD conditions was significantly higher, indicating a functional role for posture balance. These findings shed light on electrodynamic connectivity which varies in response to postural demand. Those dynamics, particularly in the θ-band connectivity, can be used for ongoing monitoring and/or intervention for postural disability.
Double training reveals an interval-invariant subsecond temporal structure in the brain
Authors: Guan Shu-Chen , Xiong Ying-Zi , Yu Cong 
Published: May 2024

AbstractSubsecond temporal perception is critical for understanding time-varying events. Many studies suggest that subsecond timing is an intrinsic property of neural dynamics, distributed across sensory modalities and brain areas. Furthermore, we hypothesize the existence of a more abstract and conceptual representation of subsecond time, which may guide the temporal processing of distributed mechanisms. However, one major challenge to this hypothesis is that learning in temporal interval discrimination (TID) consistently fails to transfer from trained intervals to untrained intervals. To address this issue, here we examined whether this interval specificity can be removed with double training, a procedure we originally created to eliminate various specificities in visual perceptual learning. Specifically, participants practiced the primary TID task, the learning of which per se was specific to the trained interval (e.g., 100 ms). In addition, they also received exposure to a new interval (e.g., 200 ms) through a secondary and functionally independent tone-frequency discrimination (FD) task. This double training successfully enabled complete transfer of TID learning to the new interval, indicating that training improved an interval-invariant component of temporal interval perception, which supports our general proposal of an abstract and conceptual representation of subsecond time in the brain.
Relationships between arts participation, social cohesion, and wellbeing: An integrative review and conceptual model
Authors: Sonke Jill , Pesata Virginia , Colverson Aaron , Morgan-Daniel Jane , Rodriguez Alexandra K. , Carroll Gray Davidson , Burch Shanaé , Abraham Abel , Akram Seher , Marjani Stefany , Belden Cassandra , Karim Hiba 
Published: May 2024

AbstractArts and cultural strategies have increasingly been engaged by the public health sector to enhance social cohesion, health, and wellbeing, as well as to address the significant health risks posed by social isolation and loneliness. While increasing studies document relationships between arts participation, social cohesion, and wellbeing uniquely, few studies have investigated the relationships between all three and, to date, no evidence synthesis has been conducted on this topic. To address this gap, this integrative review aimed to identify, describe, and synthesize research on arts participation, social cohesion, and wellbeing in a community context by addressing the question: what is the evidence base regarding relationships between arts participation, social cohesion, and well-being? Literature searches were conducted using 10 databases, and 18 articles met inclusion criteria – 16 original research articles and two reviews. Results provide insights on modes and forms of arts participation used, and offer four themes that articulate dimensions of and relationships between arts participation, social cohesion, and well-being, as distilled from the studies. Further, this review offers a conceptual model derived from these themes. The model depicts the relationships found between these concepts in the articles and highlights specific components of these relationships that may help to guide future practice, research, and policy that seeks to leverage the power of the arts to build social cohesion and wellbeing in communities. Prospective studies are needed to test these relationships as well as the potential role of social cohesion as a mechanism for building well-being in communities.
Factors influencing long-term recovery in critically ill COVID-19 survivors: A prospective multicentre cohort study
Authors: Didriksson Ingrid , Frigyesi Attila , Spångfors Martin , Leffler Märta , Reepalu Anton , Nilsson Anna , Annborn Martin , Lybeck Anna , Friberg Hans , Lilja Gisela 
Published: May 2024

AbstractBackgroundLong-term outcomes after critical COVID-19 have not been sufficiently studied. This study aimed to describe changes in functional outcome and health-related quality of life (HRQoL) assessed at 3 and 12 months in a cohort of critically ill COVID-19 survivors. A secondary aim was to investigate factors associated with good functional outcome and HRQoL at 12 months.MethodsThis prospective multicentre cohort study included critically ill COVID-19 patients admitted to six intensive care units in Sweden between May 2020 and May 2021. Surviving patients were invited to face-to-face follow-ups at 3 and 12 months. A good functional outcome was a Glasgow outcome scale extended ≥7. HRQoL was assessed by the physical and mental component summary of the SF-36v2®, with T-scores ≥45 representing a good HRQoL. Factors associated with good functional outcome and HRQoL at 12 months were explored by multivariable logistic regression.ResultsA good functional outcome was found in 93/264 (35%) and 138/217 (64%) of survivors at 3 and 12 months, respectively. There was a significant improvement in the SF-36v2® Physical component summary (PCS) between 3 and 12 months (mean 40 versus 44, p<0.001). The SF-36v2® Mental component summary (MCS) was within the normal range at 3 months, with no significant change at 12 months (mean 46 versus 48, p=0.05). Older age was associated with a good functional outcome. Low clinical frailty and absence of diabetes mellitus were associated with a good physical HRQoL. A shorter duration of mechanical ventilation was associated with a good outcome for all three outcome measures.ConclusionBetween 3 and 12 months, functional outcome and physical aspects of HRQoL significantly improved, indicating continued recovery up to at least one year after critical COVID-19. Low frailty, less comorbidity, and shorter duration of mechanical ventilation were associated with better long-term outcomes, while old age was associated with better functional outcome.Study registrationClinicalTrials.govIdentifier:NCT04974775, registered April 28, 2020.
Early detection of Alzheimer’s disease pathophysiology using 3D virtual reality navigation: a correlational study with genetic and plasma biomarkers
Authors: Shima Sayuri , Ohdake Reiko , Mizutani Yasuaki , Tatebe Harutsugu , Koike Riki , Kasai Atsushi , Bagarinao Epifanio , Ueda Akihiro , Ito Mizuki , Hata Junichi , Ishigaki Shinsuke , Tokuda Takahiko , Takashima Akihiko , Watanabe Hirohisa 
Published: May 2024

ABSTRACTBACKGROUNDWe investigated the association between path-integration (PI) errors related to entorhinal cortex function detectable using a 3D virtual reality (VR) navigation system and various biomarkers to explore its potential as an early AD indicator.METHODSThe PI capabilities of 111 healthy adults were assessed using a head-mounted 3D VR system. Demographic and cognitive assessments, AD-related plasma biomarkers, and apolipoprotein E genotypes were also evaluated. Predictive factors for PI errors were identified using multivariate linear regression, logistic regression, and random forest.RESULTSPI errors positively correlated with age, plasma levels of glial fibrillary acidic protein [GFAP], neurofilament light, and p-tau181. Multivariate analysis identified plasma GFAP and p-tau181 levels as significant predictors. Random forest analysis and receiver operating characteristic curves underscored plasma p-tau181 levels as the most substantial predictor.DISCUSSIONPI errors, particularly in conjunction with plasma p-tau181 levels, could reflect early AD pathophysiology, highlighting their potential as early biomarkers.
DROP-DEEP: Dimensionality Reduction for Polygenic Risk Score Using Deep Learning Approach
Authors: Kaufman Hadasa , Hochenberg Yarden , Linial Michal , Rappoport Nadav 
Published: May 2024

AbstractMotivationAdvances in sequencing technologies have enabled the early detection of genetic diseases and the development of personalized medicine. However, the variance explained by genetic variations is typically small compared to the heritability estimates. Consequently, there is a pressing need to develop enhanced polygenic risk score (PRS) prediction models. We seek an approach that transcends the limitations of the routinely used additive model for PRS.ResultsHere we present DROP-DEEP, a novel method for calculating PRS that enhances the explanation of the heritability variance of complex traits by incorporating high-dimensional genetic interactions. The first stage of DROP-DEEP employs an unsupervised approach to reduce dimensionality, while the second stage involves training a prediction model using a supervised machine-learning algorithm. Notably, the first stage of training is phenotype-agnostic. Thus, while it is computationally intensive, it is performed only once. Its output can serve as input for predicting any chosen trait or disease. We evaluated the efficacy of the DROP-DEEP dimensionality reduction models using principal component analysis (PCA) and deep neural networks (DNN). All models were trained using the UK Biobank (UKB) dataset with over 340,000 subjects and a set of approximately 460,000 single nucleotide variants (SNVs) across the genome. The results of DROP-DEEP, which was established for patients diagnosed with hypertension, outperformed other approaches. We extended the analysis to include an additional five binary and continuous phenotypes, each repeated five times for reproducibility assessment. For each phenotype, DROP-DEEP results were compared to commonly used PRS methodologies, and the performance of all models was discussed.ConclusionOur approach overcomes the need for variable selection while maintaining computational feasibility. We conclude that the DROP-DEEP approach exhibits significant advantages compared to commonly used PRS methods and can be used efficiently for hundreds of genetic traits.Availability and ImplementationAll the codes and the trained dimensionality reduction models are available at:https://github.com/HadasaK1/DROP-DEEP.
Reduction of Neuroinflammation and Seizures in a Mouse Model of CLN1 Batten Disease using the Small Molecule Enzyme Mimetic, N-Tert-Butyl Hydroxylamine
Authors: Fyke Zach , Johansson Rachel , Scott Anna I. , Wiley Devin , Chelsky Daniel , Zak Joseph D. , Nakouzi Nader Al , Koster Kevin P. , Yoshii Akira 
Published: May 2024

AbstractInfantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in theCLN1gene, which encodes the depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results in death, typically before fifteen years of age. Histopathological features of CLN1 include aggregation of lysosomal autofluorescent storage material (AFSM), as well as profound gliosis. The current management of CLN1 is relegated to palliative care. Here, we examine the therapeutic potential of a small molecule PPT1 mimetic, N-tert-butyl hydroxylamine (NtBuHA), in aCln1−/−mouse model. Treatment with NtBuHA reduced AFSM accumulation both in vitro and in vivo. Importantly, NtBuHA treatment inCln1−/−mice reduced neuroinflammation, mitigated epileptic episodes, and normalized motor function. Live cell imaging ofCln1−/−primary cortical neurons treated with NtBuHA partially rescued aberrant synaptic calcium dynamics, suggesting a potential mechanism contributing to the therapeutic effects of NtBuHA in vivo. Taken together, our findings provide supporting evidence for NtBuHA as a potential treatment for CLN1 Batten Disease.
First Detection of Recombinant Enterovirus G Carrying a Torovirus Papain-like cysteine protease Gene from India
Authors: Sawant PM , Lavania M , Kulkarni A 
Published: May 2024

AbstractEnterovirus G (EV-G) comprising 20 genotypes (G1-G20) are associated with in a various disease conditions in pig populations. The recombination between homologous EV-G is a driving force behind evolution but the recombination with virus from heterologous family is rare event. Presently, two types of recombinant EV-G strains containing torovirus papain like cysteine protease (PLCP) at 2C-3A junction (Type I) and in place of structural proteins (Type II) are reported. The present study conducted to reveal RNA virome in diarrheic piglet’s faeces retrieved genome coding for complete polyprotein of EV-G1. The detected EV-G1 strain represents first type I recombinant from India. The polyprotein of strain exhibiting 97% amino acid identity was closely related with Chinese strain. Furthermore, the EV-G1-PLCP strain was found to be originated from South Korean, Chinese, and Japanese strains with breakpoints at nucleotide (nt) position 1323 and 4725. Genetic and phylogenetic analysis of VP1 and PLCP of study strain demonstrated its closeness to EV-G1-PLCP strains from South Korea KOR/KNU-1811/2018/G1-PLCP. The present study advances the knowledge about genetic evolution of EV-G from gaining virulence gene from different virus family.
CD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies
Authors: Richard Jonathan , Sannier Gérémy , Zhu Li , Prévost Jérémie , Marchitto Lorie , Benlarbi Mehdi , Beaudoin-Bussières Guillaume , Kim Hongil , Sun Yaping , Chatterjee Debashree , Medjahed Halima , Bourassa Catherine , Delgado Gloria-Gabrielle , Dubé Mathieu , Kirchhoff Frank , Hahn Beatrice H. , Kumar Priti , Kaufmann Daniel E. , Finzi Andrés 
Published: May 2024

SUMMARYHIV-1 envelope glycoprotein (Env) conformation substantially impacts antibody-dependent cellular cytotoxicity (ADCC). Envs from primary HIV-1 isolates adopt a prefusion “closed” conformation, which is targeted by broadly-neutralizing antibodies (bnAbs). CD4 binding drives Env into more “open” conformations, which are recognized by non-neutralizing Abs (nnAbs). To better understand Env-Ab and Env-CD4 interaction in CD4+ T cells infected with HIV-1, we simultaneously measured antibody binding and HIV-1 mRNA expression using multiparametric flow cytometry and RNA-flow fluorescentin situhybridization (FISH) techniques. We observed thatenvmRNA is almost exclusively expressed by HIV-1 productively-infected cells that already downmodulated CD4. This suggest that CD4 downmodulation precedesenvmRNA expression. Consequently, productively-infected cells express “closed” Envs on their surface, which renders them resistant to nnAbs. Cells recognized by nnAbs were allenvmRNA negative, indicating Ab binding through shed gp120 or virions attached to their surface. Consistent with these findings, treatment of HIV-1 infected humanized mice with the ADCC mediating nnAb A32 failed to lower viral replication or reduce the size of the viral reservoir. These findings confirm the resistance of productively-infected CD4+ T cells to nnAbs-mediated ADCC and question the rationale of immunotherapy approaches using this strategy.Graphical abstract
Nanoscale analysis of functionally diverse glutamatergic synapses in the neocortex reveals input and layer-specific organization
Authors: Jones Grace , Akter Yeasmin , Shifflett Victoria , Hruska Martin 
Published: May 2024

AbstractDiscovery of synaptic nanostructures suggests a molecular logic for the flexibility of synaptic function. We still have little understanding of how functionally diverse synapses in the brain organize their nanoarchitecture due to challenges associated with super-resolution imaging in complex brain tissue. Here, we characterized single-domain camelid nanobodies for the 3D quantitative multiplex imaging of synaptic nano-organization in 6 µm brain cryosections using STED nanoscopy. We focused on thalamocortical (TC) and corticocortical (CC) synapses along the apical-basal axis of layer 5 pyramidal neurons as models of functionally diverse glutamatergic synapses in the brain. Spines receiving TC input were larger than CC spines in all layers examined. However, TC synapses on apical and basal dendrites conformed to different organizational principles. TC afferents on apical dendrites frequently contacted spines with multiple aligned PSD-95/Bassoon nanomodules, which are larger. TC spines on basal dendrites contained mostly one aligned PSD-95/Bassoon nanocluster. However, PSD-95 nanoclusters were larger and scaled with spine volume. The nano-organization of CC synapses did not change across cortical layers. These results highlight striking nanoscale diversity of functionally distinct glutamatergic synapses, relying on afferent input and sub-cellular localization of individual synaptic connections.
Amyloid Accelerator Polyphosphate Implicated as the Mystery Density in α-Synuclein Fibrils
Authors: Huettemann Philipp , Mahadevan Pavithra , Lempart Justine , Tse Eric , Dehury Budheswar , Edwards Brian F. P. , Southworth Daniel R. , Sahoo Bikash R. , Jakob Ursula 
Published: May 2024

AbstractAberrant aggregation of α-Synuclein is the pathological hallmark of a set of neurodegenerative diseases termed synucleinopathies. Recent advances in cryo-electron microscopy have led to the structural determination of the first synucleinopathy-derived α-Synuclein fibrils, which contain a non-proteinaceous, “mystery density” at the core of the protofilaments, hypothesized to be highly negatively charged. Guided by previous studies that demonstrated that polyphosphate (polyP), a universally conserved polyanion, significantly accelerates α-Synuclein fibril formation, we conducted blind docking and molecular dynamics simulation experiments to model the polyP binding site in α-Synuclein fibrils. Here we demonstrate that our models uniformly place polyP into the lysine-rich pocket, which coordinates the mystery density in patient-derived fibrils. Subsequentin vitrostudies and experiments in cells revealed that substitution of the two critical lysine residues K43 and K45 leads to a loss of all previously reported effects of polyP binding on α-Synuclein, including stimulation of fibril formation, change in filament conformation and stability as well as alleviation of cytotoxicity. In summary, our study demonstrates that polyP fits the unknown electron density present inin vivoα-Synuclein fibrils and suggests that polyP exerts its functions by neutralizing charge repulsion between neighboring lysine residues.
IL-13 and IL-17A Activate β1 Integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to Enhance Force Transmission in Airway Smooth Muscle
Authors: Ngo Uyen , Shi Ying , Woodruff Prescott , Shokat Kevan , DeGrado William , Jo Hyunil , Sheppard Dean , Sundaram Aparna B. 
Published: May 2024

ABSTRACTIntegrin activation resulting in enhanced adhesion to the extracellular matrix plays a key role in fundamental cellular processes. Although G-protein coupled receptor-mediated integrin activation has been extensively studied in non-adherent migratory cells such as leukocytes and platelets, much less is known about the regulation and functional impact of integrin activation in adherent stationary cells such as airway smooth muscle. Here we show that two different asthmagenic cytokines, IL-13 and IL-17A, activate type I and IL-17 cytokine receptor families respectively, to enhance adhesion of muscle to the matrix. These cytokines also induce activation of β1 integrins as detected by the conformation-specific antibody HUTS-4. Moreover, HUTS-4 binding is significantly increased in the smooth muscle of patients with asthma compared to healthy controls, suggesting a disease-relevant role for aberrant integrin activation. Indeed, we find integrin activation induced by a β1 activating antibody, the divalent cation manganese, or the synthetic peptide β1-CHAMP, dramatically enhances force transmission in collagen gels, mouse tracheal rings, and human bronchial rings even in the absence of cytokines. We further demonstrate that cytokine-induced activation of β1 integrins is regulated by a common pathway of NF-kB-mediated induction of RhoA and its effector Rho kinase, which in turn stimulates PIP5K1γ-mediated synthesis of PIP2resulting in β1 integrin activation. Taken together, these data identify a previously unknown pathway by which type I and IL-17 cytokine receptor family stimulation induces functionally relevant β1 integrin activation in adherent smooth muscle and help explain the exaggerated force transmission that characterizes chronic airways diseases such as asthma.SIGNIFICANCE STATEMENTIntegrin activation plays a central role in regulating cellular adhesion and migration. While chemokine-mediated integrin activation has been extensively studied in circulating cells, the role and impact of other cytokine families on non-migratory cells remains incompletely characterized. Here, we demonstrate in airway smooth muscle that asthmagenic cytokines IL-13 and IL-17A stimulate type I and IL-17 cytokine receptor families to induce β1 integrin activation and enhance adhesion. We also identify a common pathway linking NF-kB/RhoA/Rho kinase with PIP5K1γ/PIP2/β1 integrin activation. We show that airway biopsies from asthmatic patients have increased active β1 integrin staining in the muscle, and furthermore that β1 integrin activation alone dramatically enhances force transmission, underscoring the disease-relevant impact of cytokine-mediated integrin activation in adherent muscle.