bluuebunny/crossref_metadata_2025 huggingface dataset:
Interim Effectiveness of the Influenza Vaccine for the 2024-2025 Respiratory Viral Season
Authors: Shrestha Nabin K. , Burke Patrick C. , Nowacki Amy S. , Gordon Steven M.
Published: February 2025

Background

The purpose of this study was to evaluate the effectiveness of the influenza vaccine during the 2024-2025 viral respiratory season.

Methods

Employees of Cleveland Clinic in employment in Ohio on October 1, 2024, were included. The cumulative incidence of influenza among those in the vaccinated and unvaccinated states was compared over the following weeks. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for age, sex, job type, employment location, and eagerness to get vaccinated.

Results

Among 53321 employees, 43771 (82.1%) had received the influenza vaccine by the end of the study. Influenza occurred in 324 (0.6%) during the study. In an analysis adjusted for age, sex, job type, employment location, and eagerness to get vaccinated, the risk of influenza was not significantly different between the vaccinated and unvaccinated states (HR, 1.10; 95% C.I., .77 - 1.57;P= 0.59), yielding a calculated vaccine effectiveness of −10.1% (95% C.I. −57.0 - 22.7%).

Conclusions

This study has been unable to find that the influenza vaccine given to working-aged adults has provided protection overall against influenza during the 2024-2025 respiratory viral season thus far.

Among 53321 working-aged Cleveland Clinic employees, we were unable to find that the influenza vaccine has been effective in preventing infection during the 2024-2025 respiratory viral season thus far.
xOmicsShiny: an R shiny application for cross-omics data analysis and pathway mapping
Authors: Gao Benbo , Sun Yu H. , Zhang Xinmin , Lin Tinchi , Li Wei , Admanit Romi , Zhang Baohong
Published: February 2025

We developed xOmicsShiny, a feature-rich R Shiny-powered application that enables biologists to fully explore omics datasets across experiments and data types, with an emphasis on uncovering biological insights at the pathway level. The data merging feature ensures flexible exploration of cross-omics data, such as transcriptomics, proteomics, metabolomics, and lipidomics. The pathway mapping function covers a broad range of databases, including WikiPathways, Reactome, and KEGG pathways. In addition, xOmicsShiny offers several visualization options and analytical tasks for everyday omics data analysis, namely, PCA, Volcano plot, Venn Diagram, Heatmap, WGCNA, and advanced clustering analyses. The application employs customizable modules to perform various tasks, generating both interactive plots and publication-ready figures. This dynamic, modular design overcomes the issue of slow loading in R Shiny tools and allows it to be readily expanded by the research and developer community.

Availability and implementation

The R Shiny application is publicly available at:http://xOmicsShiny.bxgenomics.com. Researchers can upload their own data to the server or use the pre-loaded demo dataset. The source code, under MIT license is provided athttps://github.com/interactivereport/xOmicsShinyfor local installation. A full tutorial of the application is available athttps://interactivereport.github.io/xOmicsShiny/tutorial/docs/index.html.

Contact

yuhenry.sun@biogen.comorbaohong.zhang@biogen.com

Supplementary data

Supplementary data are available atbioRxivonline.
Model predictive game control for personalized and targeted interactive assistance
Authors: Hafs Abdelwaheb , Farr Anaïs , Verdel Dorian , Bruneau Olivier , Burdet Etienne , Berret Bastien
Published: February 2025

Contact robots are increasingly used to assist humans in physical training and manufacturing tasks. However, the effectiveness of current systems is limited as their control focuses on the system performance without explicitly considering the upcoming human user’s control. Here we present a differential game-based controller for contact robots that ensures optimal interaction with the human user by predicting their control during movement while considering their inherently finite planning horizon. Using this model-predictive game (MPG) controller, we systematically investigated human-robot co-adaptation in experiments, demonstrating that: (a) interaction with MPG remains stable for all participants while effectively reducing human effort; (b) the robot adapts to human behavior, identifying and characterizing individual motor control strategies that remain consistent over time and may be used as control biomarkers; (c) the human adapts to the robot’s behavior, and their interaction behavior can be modulated through an assistance meta-parameter. These findings indicate that humans can understand and adapt to a partner’s control strategy during movement, thereby exhibiting behavior consistent with game theory principles. Furthermore, the ability of the assistance meta-parameter to guide human users toward specific interaction behaviors can be used to develop versatile robot-assisted learning systems for physical training and rehabilitation.
Learning single-cell spatial context through integrated spatial multiomics with CORAL
Authors: He Siyu , Bieniosek Matthew , Song Dongyuan , Zhou Jingtian , Chidester Benjamin , Wu Zhenqin , Boen Joseph , Sharma Padmanee , Trevino Alexandro E. , Zou James
Published: February 2025

Cellular organization is central to tissue function and homeostasis, influencing development, disease progression, and therapeutic outcomes. The emergence of spatial omics technologies, including spatial transcriptomics and proteomics, has enabled the integration of molecular and histological features within tissues. Analyzing these multimodal data presents unique challenges, including variable resolutions, imperfect tissue alignment, and limited or variable spatial coverage. To address these issues, we introduce CORAL, a probabilistic deep generative model that leverages graph attention mechanisms to learn expressive, integrated representations of multimodal spatial omics data. CORAL deconvolves low-resolution spatial data into high-resolution single-cell profiles and detects functional spatial domains. It also characterizes cell-cell interactions and elucidates disease-relevant spatial features. Validated on synthetic data and experimental datasets, including Stero-CITE-seq data from mouse thymus, and paired CODEX and Visium data from hepatocellular carcinoma, CORAL demonstrates robustness and versatility. In hepatocellular carcinoma, CORAL uncovered key immune cell subsets that drive the failure of response to immunotherapy, highlighting its potential to advance spatial single-cell analyses and accelerate translational research.
Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats
Authors: Fuini Evan , Chang Arnold , Ortiz Richard J. , Nasseef Taufiq , Edwards Josh , Latta Marc , Gonzalez Elias , Woodward Taylor J. , Bradshaw Heather B. , Axe Bryce , Maheswari Ashwath , Cavallaro Noah , Kulkarni Praveen P. , Ferris Craig F.
Published: February 2025

Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Females were significantly more sensitive to the 0.3 mg/kg dose of psilocybin than males. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli such as the claustrum and the cortico-basal ganglia-thalamic-cortical loop were all affected by psilocybin in a dose-dependent manner. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.
BTK-NLRP3-Caspase1 and Gasdermin D-Caspase 11 pathways jointly drive neuroinflammation and functional impairments in a rat model of psychosocial stress
Authors: Tiwari Soni , Mohammad Zaidan , Atta Santi Ranjan , Kaushik Shweta , Tiwari Aryan , Chopra Amla , Singh Itender , Ghosh Simantini
Published: February 2025

Common psychological disorders related to stress, depression and anxiety pose serious disease and economic burden globally and especially in lower and lower middle-income countries. Existing pharmacotherapies mostly target neurotransmitter systems and are partially effective across a range of diagnostic categories. However, it is also a long-standing finding that a low grade inflammation in persistently present in systemic circulation as well as in the brain in stress, depression and anxiety. Specifically, neuroinflammation driven by Interleukin-1β (IL-1β) a pleiotropic cytokine. has recently been the focus of keen interest in stress, depression and anxiety research. IL-1β is probably the most prominent proinflammatory cytokine in the brain and has been long associated with these conditions. We focus on molecules that cause IL-1β to be synthesized from its precursor, namely Caspase 1, through activation of a large multiprotein complex known as the NLRP3 inflammasome complex. Using two different rat models of physical and psychosocial stress, we validate our earlier findings of the induction of the BTK/NLRP3/Caspase 1 Canonical Pathway in stressed animals. We also show the involvement of Gasdermin D/Caspase11 driven non canonical pathway that contributes to enhanced leakage of IL-1β from cells through pyroptosis, in the absence of lytic cell death. Stressed rats display a robust neuroinflammatory phenotype, reduction in CA3 Hippocampal spine density, as well as number of mature mushroom spines, and functional impairments across multiple domains of behavior. Finally we employ two FDA approved drugs, Ibrutinib and Disulfiram to partially mitigate the neural, neuroinflammatory phenotype as well as behavioral dysfunctions, individually and in combination. The combination therapy proved to be more efficacious, suggesting a joint inhibition of the canonical and non canonical pathway mitigates the pathological as well as behavioral sequelae of psychosocial stress. Taken together our data provides robust preclinical data and argues for amelioration of the NLRP3 dependent IL-1β release to be considered as an alternative therapeutic strategy in stress, depression and anxiety.
Community-acquired pneumonia identification from electronic health records in the absence of a gold standard: a Bayesian latent class analysis
Authors: Wei Jia , Yuan Kevin , Luk Augustine , Sarah Walker A , Eyre David W
Published: February 2025

Background

Community-acquired pneumonia (CAP) is common and a significant cause of mortality. However, CAP surveillance commonly relies on diagnostic codes from electronic health records (EHRs), whose accuracy is imperfect.

Methods

We used Bayesian latent class models to assess the accuracy of CAP diagnostic codes in the absence of a gold standard and to explore the contribution of various EHR data sources in improving CAP identification. Using records from 491,681 hospital admissions in Oxfordshire, UK, from 2016 to 2023, we investigated four EHR-based algorithms for CAP detection based on 1) primary diagnostic codes, 2) clinician-documented indications for antibiotic prescriptions, 3) radiology free-text reports, and 4) vital signs and blood tests.

Results

The estimated prevalence of CAP as the reason for emergency hospital admission was 13.2% (95% credible interval 12.8-13.6%). Primary diagnostic codes had low sensitivity but a high specificity (best fitting model, 0.283 and 0.997 respectively), as did vital signs with blood tests (0.242 and 0.988). Antibiotic indication text had a higher sensitivity (0.603) but a lower specificity (0.981), with radiology reports intermediate (0.493 and 0.959). Defining CAP as present when detected by any algorithm produced sensitivity and specificity of 0.854 and 0.925 respectively. Results remained consistent using alternative priors and in sensitivity analyses.

Conclusion

Relying solely on diagnostic codes for CAP surveillance leads to substantial under-detection; combining EHR data across multiple algorithms enhances identification accuracy. Bayesian latent class analysis-based approaches could improve CAP surveillance and epidemiological estimates by integrating multiple EHR sources, even without a gold standard for CAP diagnosis.
Mpox Knowledge, Risk Perception, Attitudes and Willingness to Vaccinate in Colombia’s LGBTIQ+ Communities: Online Survey (CoSex)
Authors: Diaz-Brochero Cándida , Barriga Miguel , Ramirez John Fredy , Quevedo David Santiago , Gomez Geraldine , Mateus Juliana , Nino-Machado Natalia , Cuervo-Rojas Juliana , Cucunubá Zulma M.
Published: February 2025

Background

In the 2022-23 global clade IIb mpox outbreak, Colombia was the sixth country with the most reported cases globally and the second in Latin America after Brazil. LGTBIQ+ communities, especially those with extensive sexual networks, were particularly affected.

Objective

We aim to characterize the knowledge, risk perceptions, attitudes, and willingness to implement preventive measures against mpox among LGBTIQ+ communities in Colombia.

Methods

This was an anonymized, cross-sectional, observational study based on a population-based online questionnaire using a participatory approach.

Results

Among 784 participants from 66 municipalities, 49.1% were aged 18–29 years, and 89.3% were male assigned at birth. A total of 73.9% identified as homosexual, while 14.9% reported never using condoms. Casual sexual partners were reported by 45.4% in the past year (median: 3; range: 1–100), and 29.3% engaged in group sex during the same period (median: 4; range: 2–100). Temporary behavioral changes to reduce mpox risk, such as limiting sexual partners and increasing condom use, were reported by 24.1%. Suspected or confirmed mpox infection was reported by 4% of participants, with 77.4% attributing potential exposure to sexual contact. Notably, 89.5% expressed willingness to receive mpox vaccination if offered.

Conclusions

Our findings demonstrate the importance of academic and social communities’ cross-collaboration to understand the impact of mpox infection in this population and as a basis for planning epidemic responses to future mpox outbreaks in Colombia and Latin America.
Recovery of intrinsic cognitive weakness in successive processing after bypass surgery for pediatric moyamoya disease
Authors: Chihara Hideo , Funaki Takeshi , Kusano Yusuke , Hidaka Yu , Mineharu Yohei , Okawa Masakazu , Sasagasako Tomoki , Sawada Masahiro , Kikuchi Takayuki , Tanaka Kanade , Nishida Noyuri , Tabata Ami , Ueda Keita , Ueno Tsukasa , Arakawa Yoshiki
Published: February 2025

Background

Successive processing, a form of working memory function detected with the Das Naglieri Cognitive Assessment System (CAS), is selectively impaired in pediatric moyamoya disease (MMD). We aimed to test whether successive processing in children with MMD was improved after bypass surgery under the control of confounding.

Methods

The present retrospective cohort study included children with MMD who underwent direct or combined bypass surgery. Neuropsychological tests including the CAS were administered at two timepoints, before and after surgery, approximately one year apart. The least squares (LS) mean standard score and LS mean difference between timepoints were calculated using a mixed model for repeated measures, which included five clinical factors along with the timepoint. Models including an interaction term were also generated to assess the effect of each clinical factor. Cognitive intra-individual variability across four domains of the CAS was assessed with an analysis of variance at each timepoint.

Results

Of 60 patients who underwent surgery, 42 fulfilled the inclusion criteria. The median duration between assessments was 15 months. The LS mean standard scores of successive processing increased after surgery (LS mean, 95.8 versus 100.2; LS mean difference, 4.4 [95% CI, 1.5–7.3];P= 0.004). The increase was more pronounced in those with younger age at onset, shorter delay before surgery, pre-existing infarct, posterior cerebral artery involvement, and severer ischemic stage before surgery. Intra-individual variability, shown as the lowest score of successive processing at baseline, resolved after surgery (F= 3.56,P= 0.016 versusF= 1.21,P= 0.31). Successive processing was the domain most likely to be improved after surgery.

Conclusions

The present results suggest that successive processing is improved after bypass surgery. Larger and longer follow-up studies are required to confirm the influencing factors and long-term effect.
Functional Interrogation of Neuronal Subtypes via Intersectional Expression of Optogenetic Actuator Reveals Non-linear Components in a Linear Circuit
Authors: Li Tiannuo , Kumar Sandeep , Poon Hoikiu , Leifer Andrew M , Zheng Chaogu
Published: February 2025

Investigating signal integration in a neural circuit is oftentimes challenging when the circuit contains neuronal subtypes that are transcriptomically similar, due to the lack of tools to express optogenetic actuators with high cellular specificity and to deliver light with high spatiotemporal accuracy. Here, we demonstrate the use of a split GAL4-based genetic “AND” gate to express Chrimson in specific touch receptor neuron (TRN) subtypes in theC. eleganstouch response circuit. Combining this intersectional strategy for transgene expression with high-throughput optical targeting and behavioral quantification, we optogenetically interrogated the role of each TRN subtype in mediating the mechanosensor-induced escape response and in integrating signals that trigger the opposite motor output. Surprisingly, we found that although the response of the overall circuit linearly combines the competing anterior and posterior stimuli, this linearity is comprised of antagonistic non-linear contributions from the anterior and posterior sensors, which conspire to generate a linear response.
P3a site-specific and cassette mutagenesis for seamless protein and plasmid engineering
Authors: Yang Xiang-Jiao
Published: February 2025

Site-directed mutagenesis is a basic molecular tool required for protein and plasmid engineering. We have recently adopted an innovative strategy using primer pairs with 3-prime overhangs and developed an optimized protocol, referred to as P3 site-directed mutagenesis, with an efficiency of ~50%. This raises the important question how to enhance the efficiency to the ideal level of 100%. Here we report P3a site-directed mutagenesis with an efficiency at or close to 100% and have systematically evaluated this improved method by engineering >100 point mutations and small deletions (or insertions) on >20 mammalian expression vectors encoding various epigenetic regulators and the spike protein of SARS-CoV-2. Moreover, all known mutagenesis methods are limited to point mutations and small deletions/insertions (typically up to a dozen nucleotides), raising the technical problem how to carry out cassette mutagenesis for replacement, deletion or insertion of large DNA fragments. Accordingly, the high efficiency of P3a mutagenesis and the handshaking feature of primer pairs with 3-prime overhangs have inspired us to adapt this method for efficient and seamless cassette mutagenesis, including high efficiency in epitope tagging and untagging, deletion of small and large DNA fragments and insertion of oligonucleotide duplexes (such as LoxP sites and sgRNA-coding sequences). Thus, this new site-specific and cassette mutagenesis method is highly efficient, likely resulting in its wide use for biomedical research.
Interferometric Ultra-High Resolution 3D Imaging through Brain Sections
Authors: Gao Hao-Cheng , Xu Fan , Cheng Xi , Bi Cheng , Zheng Yue , Li Yilun , Chen Tailong , Li Yumian , Chubykin Alexander A. , Huang Fang
Published: February 2025

Single-molecule super-resolution microscopy allows pin-pointing individual molecular positions in cells with nanometer precision. However, achieving molecular resolution through tissues is often difficult because of optical scattering and aberrations. We introduced 4Pi single-molecule nanoscopy for brain within-situpoint spread function retrieval through opaque tissue (4Pi-BRAINSPOT), integrating 4Pi single-molecule switching nanoscopy with dynamicin-situcoherent PSF modeling, single-molecule compatible tissue clearing, light-sheet illumination, and a novel quantitative analysis pipeline utilizing the highly accurate 3D molecular coordinates. This approach enables the quantification of protein distribution with sub-15-nm resolution in all three dimensions in complex tissue specimens. We demonstrated 4Pi-BRAINSPOT’s capacities in revealing the molecular arrangements in various sub-cellular organelles and resolved the membrane morphology of individual dendritic spines through 50-µm transgenic mouse brain slices. This ultra-high-resolution approach allows us to decipher nanoscale organelle architecture and molecular distribution in both isolated cells and native tissue environments with precision down to a few nanometers.
Nanotribology of Viruses Reveals Their Adhesion Strength and Modality of Motion on Surfaces
Authors: Ault Charles A. , Tsvetkova Irina B , De Pablo Pedro , Simon Claudia , Dragnea Bogdan
Published: February 2025

We studied the friction dynamics of icosahedral viruses adsorbed to solid surfaces to probe their adhesion. Using the lateral torsion of cantilevers in atomic force microscopy to move individual capsids in a liquid environment, we found that the virions tend to roll rather than slide on the surface. In contrast, rigid, ligand-stabilized gold nanoparticles are more likely to combine rolling with sliding under the same conditions. The experiments indicate that the force required to drag the viruses on the surface is four times less than that of AuNPs, while the lateral force work needed to induce virus movement was ≈104kT, ten times less than that of the rigid gold nanoparticles. These results go beyond the paradigm that adhesion of nanoparticles is mainly governed by geometrical factors, such as size and area of contact, highlighting the need to amend modeling approaches to account for mechanically-compliant tribological response of biologically derived nanoparticles.
Single-cell RNA sequencing of peripheral blood mononuclear cells in patients with acutely decompensated cirrhosis reveals a specific monocyte subset associated with an increased risk of progression to ACLF
Authors: Wirtz Theresa H. , Palomino-Echeverria Sara , Pollmanns Maike R. , Huergo Estefanía , Schreibing Felix , Reißing Johanna , Sánchez-Garrido Cristina , López-Vicario Cristina , Aransay Ana M. , Baldassare Maurizio , Zaccherini Giacomo , Pompili Enrico , Schulz Martin , Uschner Frank E. , Klein Sabine , Gu Wenyi , Schierwagen Robert , Valainathan Shantha , Verbeeck Annabelle , Campion Daniela , Giovo Ilaria , Koch Alexander , Kramann Rafael , Bruns Tony , Kiani Narsis , Caraceni Paolo , Alessandria Carlo , Moreau Richard , Trebicka Jonel , Clària Joan , Planell Núria , Rautou Pierre-Emmanuel , Trautwein Christian , Gomez-Cabrero David
Published: February 2025

Background

Patients with acute decompensation (AD) of cirrhosis are at high risk of developing acute-on-chronic liver failure (ACLF), a syndrome characterized by multiple organ failure and high short-term mortality. This study aimed to analyse alterations in peripheral blood mononuclear cells (PBMCs) in patients with AD using single-cell technologies and to explore their implications for risk stratification and prognosis.

Methods

A total of 63 AD patients and 15 healthy donors were enrolled at five European centers, with blood samples collected upon hospital admission. Patients were monitored for 90 days after study inclusion, focusing on hospital readmission related to AD and the development of ACLF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) was performed on PBMCs from 16 patients (n=6 without readmission, n=6 with readmission, and n=4 with ACLF development) along with 4 healthy controls. The whole blood of the same 16 patients was assessed by bulk RNA-seq. The whole blood transcriptional profiles from two independent prospective multicentre cohorts of patients with AD (PREDICT (n=689) and ACLARA (n=521)) were included as validation cohorts.

Results

Cell proportion analysis revealed a significant increase of classical monocytes in patients with subsequent ACLF development. Notably, classical monocytes represented the cell type with the highest transcriptional alterations. Within the classical monocyte population, a specific subcluster, termed “C2”, was identified and found to be enriched during progression towards ACLF. This monocytic subpopulation was primarily characterized by decreased expression of genes encoding enzymes relevant to cellular energy supply, such as oxidative phosphorylation and ATP production. Pathway analysis confirmed a marked impairment of energy metabolism pathways within the C2 subcluster. A gene signature derived from that monocytic subpopulation was significantly increased in patients with bacterial infection, ACLF development and non-survivors of two independent multicenter cohorts of patients with AD.

Conclusion

Patients with acute decompensation of cirrhosis who subsequently develop ACLF are characterized by a subpopulation of classical monocytes exhibiting features of impaired energy metabolism pathways.
The effects of reliable social feedback on language learning: insights from EEG and pupillometry
Authors: Zappa Ana , Osokina Polina , Cerda-Company Xim , Cucurell David , Mateu Maria , Rodriguez-Fornells Antoni
Published: February 2025

Language learning is often a social process, and social feedback may play a motivational role. We examined the neurophysiological correlates of word learning with feedback varying in reliability and social content. Participants associated novel auditory words with objects and received social (video clips) or symbolic (static images) feedback. In a forced-choice task, participants learned to associate novel auditory words with known objects and received feedback that was either Social Reliable (correct), Social Unreliable (random), or Symbolic Reliable (correct). Post-training behavioral performance was better for words learned with social and symbolic reliable feedback. Stimulus-preceding negativity (SPN) and late positive complex (LPC) ERP amplitudes, as well as pupil dilation, showed differences as a function of feedback reliability and social content. In the reliable conditions, before feedback, SPN amplitude grew as learning progressed, likely due to the expectation of receiving positive feedback. During feedback, LPC amplitude for positive feedback diminished as learning progressed but not for negative feedback, which was likely consistently used for context updating. These effects were not observed for unreliable feedback, probably because its value was not used for updating information. Pupillometry results corroborated these findings, showing greater dilation for negative vs positive feedback in reliable conditions. Finally, when feedback was social, processing was associated with more frontal activation and behavioral performance was closely correlated with both ERP and pupillometry results. Overall, our findings show differential processing of feedback depending on its informational and social content, advancing our understanding of how social and cognitive processes interact to shape word learning.
Incident Atrial Fibrillation and Flutter in Patients with Pulmonary Arterial Hypertension: Influence of Right Ventricular Dilatation and Reduced Right Atrial Function
Authors: Mohama Danny , Worapongsatitaya Pitchaya , Celestin Bettia , Kazmirczak Felipe , Bagherzadeh Shadi P. , Prins Kurt W. , Prisco Sasha Z. , Weir E. Kenneth , Archer Stephen L. , Zamanian Roham , Haddad Francois , Thenappan Thenappan
Published: February 2025

Background

The relationship between right atrial (RA) structural and functional remodeling and risk of atrial fibrillation/flutter (AF/AFL) in pulmonary arterial hypertension (PAH) is understudied. This is important due to the prognostic implications of AF/AFL in PAH.

Methods

In a multicenter cohort study comprised of 326 PAH patients with no prior history of AF/AFL, we evaluated how RA structure and function, as determined by echocardiography, were associated with AF/AFL. We calculated the incident rate (IR) of AF/AFL using time to event analysis. Cox proportional hazards analyses defined factors associated with incident AF/AFL and Harrell’s C-statistics compared the ability of different variables to predict incident AF/AFL. Survival decision tree and restricted cubic spline analyses identified thresholds associated with incident AF/AFL.

Results

In the combined PAH cohort, the mean age was 51±15 years, 79% were female, and the mean REVEAL lite score was 7.4±2.9. Over a median follow-up of 6.1 years, 56 patients (17.1%) developed AF/AFL with an IR of 25.3 cases (95% CI: 19.5 - 32.8) per 1000 person-year. On multivariable Cox proportional hazards analysis, every 5% decrease in RA emptying fraction (RAEF, HR: 1.38, 95% CI: 1.03 – 1.86,p=0.030) and one centimeter increase in right ventricular (RV) basal diameter (HR: 1.55 95% CI: 1.18 – 2.05,p=0.002) were independently associated with 38% and 56% increased hazards of incident AF/AFL, respectively. The C-statistics of RAEF and RV basal diameter to predict incident AF/AFL were 0.62 and 0.65, respectively. Survival decision tree and restricted cubic spline analyses identified informative thresholds for RAEF at <17 and 45% and for RV basal diameter at ≥5.4 cm for increased hazards of incident AF/AFL.

Conclusion

Lower RAEF and higher RV basal diameter are associated with increased risk of incident AF/AFL in PAH patients. These data could help identify PAH patients at risk for AF/AFL.
External Validation, Re-Calibration, and Extension of a Prediction Model of Early Acute Kidney Injury in Critically Ill Children using Multi-Center Data
Authors: Dziorny Adam C. , Drury Stephen , Clark Alex , Farris Reid WD , Nishisaki Akira , Cornell Timothy T. , Tawfik Daniel S. , Bennett Tellen D. , Shah Sareen S. , Weiss Scott L. , Mohamed Tahagod , Shah Neel , McMahon James , Muthu Naveen , Wetzel Randall C. , Zand Martin , Nelson Sanchez-Pinto L.
Published: February 2025

Background

Acute kidney injury (AKI) is common among children with critical illness and is associated with high morbidity and mortality. Risk prediction models designed for clinical decision support implementation offer an opportunity to identify and proactively mitigate AKI risks. Existing models have been primarily validated on single-center data, owing partly to the lack of appropriately detailed multicenter datasets.

Objective

To determine the accuracy of a single-center model to predict new AKI at 72 hours of ICU admission across two multicenter datasets and extend this model to improve prediction accuracy while maintaining acceptable alert burden.

Derivation and Validation Cohorts

We separately derived models in two datasets: PEDSNET-VPS, created through the linkage of PEDSnet electronic health record (EHR) extraction with Virtual Pediatric Systems (VPS); and the PICU Data Collaborative dataset, created through EHR extraction and harmonization from eight participating institutions. Derivation datasets comprised temporal and location-specific spit of these datasets (80%), while the holdout test split comprised the remaining (20%).

Prediction Model

We recalibrated an existing single-center model and measured discrimination and accuracy. We then add features guided by precision and recall measures. All features were available at 12 hours of ICU admission. We measure discrimination and accuracy at multiple cut-points and identify the features contributing most to the risk score.

Results

In two datasets comprising 186,540 ICU admissions, we report an incidence of early AKI of 2.2 – 2.7%. Initial recalibration of an existing single-center model demonstrated poor discrimination (AUROC 0.60 – 0.78). Following the addition of new features, we report higher AUROC values of 0.79 - 0.80 and AUPRC values of 0.13 – 0.21 in both datasets. We report accuracy at several cutpoints as well as cross-validate between datasets.

Conclusions

In this first use of two new multicenter datasets, we report improved discrimination and accuracy in a model designed specifically for implementation, balancing sensitivity and precision to predict patients at risk for AKI development.
HIV, HPV, and Oral Health in Tanzania: A scoping review
Authors: Gedion Kalipa , Blackwood Elizabeth , Mwobobia Judith , Semali Innocent , Moshi Mainen Julius , Owibingire Sira , Mwaiswelo Richard O , Mashalla Yohana , Ferrari Guido , Bartlett John , Osazuwa-Peters Nosayaba
Published: February 2025

Background

There is an increased risk of human papillomavirus (HPV)-associated infections and malignancies among people living with HIV (PLHIV). However, there is limited literature exploring the intersection of HPV, HIV, and oral health in Tanzania and across sub-Saharan Africa. We reviewed the existing literature on the intersection of HIV, HPV, and oral health in Tanzania.

Methods

This was a scoping review with the search of key words representing HIV, HPV, oral health, and Tanzania. Since there were no studies that explored the intersection of HIV, HPV, and oral health in Tanzania, the search extended to include studies with the intersection between oral health and either HIV or HPV in Tanzania.

Findings

44 studies were eligible for analysis. Only one of them explored the relationship between HPV and oral health, where 4 (6%) of adolescent schoolgirls were detected with HPV-DNA and the paper hinted at the possibility of HPV autoinoculation. There were no articles linking HPV vaccination and oral health. The remaining 43 (98%) studies explored the relationship between HIV and oral health. There has been an increase in oral manifestations in PLHIV in the last two decades, and highly active antiretroviral therapy has been protective against oropharyngeal candidiasis but had no significance on head and neck cancer. Single-dose fluconazole and 35% herbal antifungals were identified to be effective in treating oral candidiasis. No recent studies explored the different facets of dental care among PLHIV.

Interpretation

There are no studies exploring the intersection of HIV, HPV, and oral health in Tanzania. Future studies are needed to determine the burden and barriers of HPV-associated oral manifestations among PLHIV in Tanzania and across Sub-Saharan Africa.
Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder
Authors: Zadka Łukasz , Eggerstorfer Benjamin , Buzalewicz Igor , Vraka Chrysoula , Rusak Agnieszka , Godbersen Godber M , Opalińska Agnieszka , Unterholzner Jakob , Ulatowska-Jarża Agnieszka , Philippe Cecile , Haczkiewicz-Leśniak Katarzyna , Silberbauer Leo R , Murgaš Matej , Nics Lukas , Hahn Andreas , Hacker Marcus , Gomułkiewicz Agnieszka , Rujescu Dan , Podhorska-Okołów Marzenna , Lanzenberger Rupert , Gryglewski Gregor
Published: February 2025

With their ability to cross the blood-brain barrier, transport and regulate the release of various signaling molecules, extracellular vesicles (EVs) constitute a novel avenue to study intercellular communication in various pathologies, including psychiatric disorders. We studied 34 major depressive disorder (MDD) patients and 57 healthy controls and characterized EVs isolated from plasma using digital holographic tomography (DHT) and nanoparticle tracking analysis (NTA). EVs detected in DHT were markedly smaller and less variable in size in MDD patients. Furthermore, a lower variance of refractive indices related to the dry mass density of EVs was observed in patients. Meanwhile, NTA revealed a trend for elevated concentration of EVs in MDD. In DHT, EV dimensions correlated with plasma mRNA expression of exosomal markersCD63andCD9, with corresponding alterations in MDD. Levels of EV concentration andCD9were both negatively correlated with antidepressant treatment response. Utilizing electron microscopy and immunoblots we confirmed the presence of serotonin transporters (SERT) as EV cargo. SERT levels in EVs correlated with cerebral SERT binding potential in the amygdala measured using positron emission tomography. Next to the implication of altered EV communication in mood disorders, the pronounced differences in plasma EV characteristics and exosomal markers in MDD might inform the development of assays with diagnostic or prognostic value for clinical practice.
Vibrio harveyiplasmids as drivers of virulence in barramundi (Lates calcarifer)?
Authors: Sullivan Roisin , Becker Joy A , Zadoks Ruth N , Venturini Carola , Esteves Ana I. S. , Benedict Suresh , Fornarino Dani L , Andrews Hannah , Okoh God’spower R , Bhardwaj Vidya , Sistrom Mark , Westman Mark E , Phuoc Nguyen Ngoc , Samsing Francisca
Published: February 2025

Vibriospecies are an emerging public and animal health risk in marine environments and the opportunistic bacterial pathogenVibrio harveyiis a major disease risk for tropical aquaculture. Current understanding of virulence inV. harveyiis limited by strain-specific variability and complex host-pathogen dynamics. This study sought to integrate genomic investigation, phenotypic characterisation andin vivochallenge trials in barramundi (Lates calcarifer)to increase our understanding ofV. harveyivirulence. We identified two hypervirulent isolates, Vh-14 and Vh-15 that caused 100% mortality in fish within 48 hours, and that were phenotypically and genotypically distinct from otherV. harveyiisolates. Virulent isolates contained multiple plasmids, including a 105,412 bp conjugative plasmid with type III secretion system genes originally identified inYersinia pestis. The emergence of this hypervirulent plasmid-mediated patho-variant poses a potential threat to the sustainable production of marine finfish in Southeast Asia, the Mediterranean and Australia. In addition, we observed an effect of temperature on phenotypic indicators of virulence with an increase in activity at 28°C and 34°C compared to 22°C. This suggests that temperature fluctuations associated with climate change may act as a stressor on bacteria, increasing virulence gene secretion and host adaptation. Our results utilising a myriad of technologies and tools, highlights the importance of a holistic view to virulence characterisation.
Dynamic context-based updating of object representations in visual cortex
Authors: Aldegheri Giacomo , Gayet Surya , Peelen Marius V.
Published: February 2025

In everyday vision, objects in scenes are often poorly or only partially visible, for example because they are occluded or appear in the periphery. Previous studies have shown that the visual system can reconstruct missing object information based on the spatial context in static displays. Real-world vision is dynamic, however, causing the visual appearance of objects (e.g., their size and viewpoint) to change as we move. Importantly, these changes are highly predictable from the 3D structure of the surrounding scene, raising the possibility that the visual cortex dynamically updates object representations using this predictive contextual information. Here, we tested this hypothesis in two fMRI studies (N=65). Experiment 1 showed that visual representations of objects were sharpened when they rotated congruently (rather than incongruently) with the surrounding scene. Moreover, Experiment 2 showed that the updated orientation of the object (as dictated by the surrounding scene) could be decoded from visual cortex activity, even when the object itself was not visible. These findings indicate that predictive processes in the visual cortex follow the geometric structure of the environment, thus providing a mechanism that leverages predictions to aid object perception in dynamic real-world environments.
EFFECT OF OMEGA 3 SUPPLEMENTATION DURING PREGNANCY AND LACTATION ON COGNITIVE FUNCTIONS IN RAT OFFSPRING
Authors: Onur Öztürk Hande Nur , Türker Perim Fatma
Published: February 2025

Aim

This study investigates the effects of omega-3 supplementation starting in the preconception period, during the 1st, 2nd, and 3rd weeks of pregnancy, and lactation on the cognitive functions of rat offspring.

Methods

The study involved 30 mother rats divided into a test group receiving 400 mg/kg/day omega-3 supplementation via oral gavage and a control group with no supplementation. Omega-3 supplementation began at different stages for each group and continued through the lactation period (21 days). Two male pups from each mother, for a total of 60 pups, were tested for cognitive function at 45 days using the Morris Water Maze to assess spatial learning and reference memory.

Results

Significant differences were found between groups in initial weights, pre-mating weights, pre-birth weights, number of pups, and gestation duration (p<0.05), but not in weight gain during pregnancy (p>0.05). The time to find the platform on test days 1 and 2 was significantly different between groups (p<0.05). Differences in platform-finding times across trials were also significant (p<0.05). However, no significant difference was found in the probe test on day 5 (p>0.05).

Conclusion

Initiating omega-3 supplementation during the early stages of pregnancy may be more effective for both short-term and long-term memory.
The role of human intraparietal sulcus in evidence accumulation revealed by EEG and model-informed fMRI
Authors: Wongtrakun Jaeger , Zhou Shou-Han , O’Connell Redmond G. , Chong Trevor T.-J. , Bellgrove Mark A. , Coxon James P.
Published: February 2025

Sequential sampling models propose that the repeated sampling of sensory information is a fundamental component of perceptual decision-making. Electroencephalographic investigations in humans have demonstrated motor-independent representations of evidence accumulation, but such observations have seldom been made in neuroimaging studies exploring the neuroanatomical origins of evidence accumulation. Here, we aimed to reveal the neuroanatomical locus of sensory evidence accumulation in the human brain by regressing an electrophysiological marker of evidence accumulation (centroparietal positivity, CPP) against changes in blood oxygen level-dependent (BOLD) signal during perceptual decision-making. Our cross-modal imaging approach revealed a cluster within left intraparietal sulcus (IPS), located within putative lateral intraparietal area (region hIP3), for which BOLD signals scaled in relation to the slope of the CPP. Furthermore, the drift rate parameter of a drift diffusion model parametrically modulated BOLD activity within an overlapping region of left IPS. In contrast, parametric modulation by reaction time revealed a distributed fronto-parietal network, demonstrating the utility of our approach for isolating a discrete neuroanatomical locus of evidence accumulation. Together, our findings provide strong support for intraparietal sulcus involvement in the accumulation of sensory evidence during human perceptual decision-making.
The role of toxin/antidote genes in the maintenance and evolution of accessory chromosomes inFusarium
Authors: Sandell Linnea , Forsythe Adrian , Mirandola Anna , Jorayev Samuel , Urquhart Andrew , Farbos Alexandra Granger , Saupe Sven J. , Vogan Aaron A.
Published: February 2025

The genomic diversity of many fungal species is augmented by accessory chromosomes, which are variably present in individual strains. These genomic regions evolve rapidly, accumulating genes important in pathogenicity but also harboring significant amounts of transposable elements (TEs). This duality suggests a trade-off: accessory chromosomes provide infection-related benefits while otherwise being deleterious due to their highly repetitive nature and contributions to genomic instability. Despite this, accessory chromosomes often appear to be stably maintained even when strains are grown on media, with no plant host. Previously, we had observed that genes homologous to meiotic drive toxin/antidote proteins fromPodospora anserina(Spoks) are abundant on accessory chromosomes in variousFusariumspecies. Using a functionality screen in yeast, we demonstrate that some of these homologs have active toxin and antidote properties. We propose that these selfish genes act to maintain accessory chromosomes during vegetative growth and may influence their spread via parasexual cycles. Finally, asSpokgenes are mobilized by the newly described TE superfamilyStarships, it suggests these TEs play crucial roles in forming accessory chromosomes and regions. These results illuminate a mysterious facet of fungal biology, a key step towards describing the origin, spread, and maintenance of pathogenicity in many fungal species.
BMAL1Overexpression in Suprachiasmatic Nucleus Protects from Retinal Neurovascular Deficits in Diabetes
Authors: Mahajan Neha , Luo Qianyi , Lukkes Jodi , Abhyankar Surabhi D , Bhatwadekar Ashay D
Published: February 2025

The suprachiasmatic nucleus (SCN) regulates circadian rhythms and influences physiological and behavioral processes. Disruptions in circadian rhythms (CRD) are observed in type 2 diabetes (T2D), and importantly, CRD acts as an independent risk factor for T2D and its associated complications. BMAL1, a circadian clock gene, is vital for sustaining an optimal circadian rhythm and physiological function. However, the therapeutic potential of BMAL1 overexpression in the SCN to rectify the neurovascular deficits of T2D has yet to be investigated. In this study, db/db mice, a well-established model of T2D exhibiting arrhythmic behavior and the complications of diabetes, were injected stereotaxically with AAV8-Bmal1 or a control virus in the SCN to evaluate the protective effects of correcting the central clock on neurovascular deficits. Given the complex neurovascular network and the eye’s unique accessibility as a transparent system, ocular complications were selected as a model to examine the neuronal functional, behavioral, and vascular benefits of correcting the central clock. BMAL1 overexpression normalized the circadian rhythms, as demonstrated by improvements in the free-running period. The retinal neuronal function improved on electroretinogram, along with optomotor behavior and visual acuity enhancements. Retinal vascular deficits were also significantly reduced. Notably, our approach helped decrease fat content in genetically predisposed obese animals. Since the SCN is known to regulate hepatic glucose production via sympathetic mechanisms, glycemic control, and pyruvate tolerance tests were conducted. Systemically, we observed improved glucose homeostasis in BMAL1-overexpressing mice alongside a substantial reduction in hepatic gluconeogenesis. BMAL1 overexpression lowered plasma norepinephrine and liver TH levels, indicating a protective regulation of adrenergic signaling. Thus, this study underscores the therapeutic potential of targeting circadian clock genes like BMAL1 in the SCN to alleviate metabolic and neurovascular deficits associated with T2D. Our research offers a compelling framework for integrating circadian rhythms into managing diabetes and its complications.