bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPsilocybin 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

AbstractCommon 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

AbstractBackgroundCommunity-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.MethodsWe 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.ResultsThe 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.ConclusionRelying 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

AbstractBackgroundIn 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.ObjectiveWe aim to characterize the knowledge, risk perceptions, attitudes, and willingness to implement preventive measures against mpox among LGBTIQ+ communities in Colombia.MethodsThis was an anonymized, cross-sectional, observational study based on a population-based online questionnaire using a participatory approach.ResultsAmong 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.ConclusionsOur 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

AbstractBackgroundSuccessive 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.MethodsThe 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.ResultsOf 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.ConclusionsThe 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

SummaryInvestigating 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.
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

AbstractSingle-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.
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

AbstractBackgroundPatients 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.MethodsA 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.ResultsCell 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.ConclusionPatients with acute decompensation of cirrhosis who subsequently develop ACLF are characterized by a subpopulation of classical monocytes exhibiting features of impaired energy metabolism pathways.
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

AbstractBackgroundThe 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.MethodsIn 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.ResultsIn 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.ConclusionLower 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

ABSTRACTBackgroundAcute 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.ObjectiveTo 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 CohortsWe 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 ModelWe 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.ResultsIn 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.ConclusionsIn 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

AbstractBackgroundThere 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.MethodsThis 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.Findings44 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.InterpretationThere 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.