bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice
Authors: Liu Jia , Lu Yan , Bhuiyan Piplu , Gruttner Jacob , Louis Lauren St. , Yi Yutong , Liang Ge , Wei Huafeng 
Published: September 2024

AbstractThis study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles pretreatment to inhibit lipopolysaccharide (LPS)-induced pathological inflammation and synapse destruction and depressive and anxiety behavior in mice. Both wild-type (WT) B6SJLF1/J and 5XFAD adult mice (5-10 months old) were pretreated with intranasal dantrolene nanoparticles (dantrolene: 5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression, anxiety and side effects were performed 24 hours after a one-time LPS injection. Biomarkers for pyroptosis-related inflammation cytokines (IL-1β and IL-18) in blood and brains were measured using enzyme-linked immunosorbent assay (ELISA) and immunoblotting, respectively. The changes of primary proteins activation inflammatory pyroptosis (NLRP3: NLR family pyrin domain containing 3, Caspase-1, N-GSDMD: N terminal protein gasdermin D) and synapse proteins (PSD-95 and synpatin-1) in brains were measured using immunoblotting. Intranasal dantrolene nanoparticles robustly inhibited LPS-induced depression and anxiety behavior in both WT and 5XFAD mice, without obvious side effects. Intranasal dantrolene nanoparticles significantly inhibited LPS-induced pathological elevation of IL-1β and IL-18 in the blood and synapse loss in the brain. Intranasal dantrolene nanoparticles trended to inhibit LPS-induced elevation of IL1β and IL-18 and the pyroptosis activation proteins in the brain in both type of mice. In conclusion, intranasal dantrolene nanoparticles demonstrated neuroprotection against inflammation mediated depression and anxiety behaviors and should be studied furthermore as a future effective drug treatment of major depression disorder or anxiety psychiatric disorder, especially in AD patients.
Structure-Based Computational Analysis of Interactions between Insulin Receptor and Insulin Inhibitory Receptor
Authors: Li Victor , Wu Yinghao 
Published: September 2024

ABSTRACTThe recently discovered insulin inhibitory receptor (inceptor) plays a crucial role in insulin resistance and diabetes by reducing the insulin receptor count on cell membranes, resulting in higher blood glucose levels and decreased insulin sensitivity. Therefore, understanding the mechanism of how the inceptor insulin receptor complex interacts is exceedingly important. This study uses computational drug discovery to inhibit this interaction. Initially, we employed AlphaFold-Multimer to model the inceptor-insulin receptor protein complex and subsequently identified specific inceptor residues likely involved in binding to the insulin receptor. Through virtual screening, thousands of potential small molecules were found to bind to the inceptor, and 10 with the highest probability were chosen for docking. Beta-L-fucose, beta-D-fucose, and alpha-L-fucose showed the most promising binding energies, meaning these three small molecules can effectively interrupt the binding between the complex. We also computationally mutated the binding site of the insulin receptor and calculated the change in binding energy of the inceptor insulin receptor complex, the most dramatic being a 0.4 kcal mol^-1 change when Arginine mutated to Tryptophan at residue 926. Our study suggests that the mutations led to disease primarily due to the change in interactions of the inceptor insulin receptor complex.
Bulk-level maps of pioneer factor binding dynamics during Drosophila maternal-to-zygotic transition
Authors: Dima Sadia Siddika , Reeves Gregory T. 
Published: September 2024

AbstractGene regulation by transcription factors (TFs) binding cognate sequences is of paramount importance. For example, the TFs Zelda (Zld) and GAGA factor (GAF) are widely acknowledged for pioneering gene activation during zygotic genome activation (ZGA) inDrosophila. However, quantitative dose/response relationships between bulk TF concentration and the DNA binding, an event tied to transcriptional activity, remain elusive. Here, we map these relationships during ZGA: a crucial step in metazoan development. To map the dose/response relationship between nuclear concentration and DNA binding, we performed raster image correlation spectroscopy, a method that can measure concentration and binding of fluorescent molecules. We found that, although Zld concentration increases over time, its DNA binding in the transcriptionally active regions decreases, consistent with its function as an activator for early genes. In contrast, GAF DNA binding is nearly linear with its concentration, which sharply increases during the major wave, implicating it in the major wave. This study provides key insights into the properties of the two factors and puts forward a quantitative approach that can be used for other TFs to study transcriptional regulation.
Scalable identification of lineage-specific gene regulatory networks from metacells with NetID
Authors: Wang Weixu , Wang Yichen , Lyu Ruiqi , Grün Dominic 
Published: September 2024

AbstractThe identification of gene regulatory networks (GRN) governing distinct cell fates in multilineage cellular differentiation systems is of critical importance for understanding cell fate decision. Single-cell RNA-sequencing (scRNA-seq) provides a powerful tool for the quantification of gene-level co-variation across the cell state manifold. However, accurate GRN reconstruction is hampered by the sparsity of scRNA-seq data introducing substantial technical noise. Moreover, the high dimensionality of typical scRNA-seq datasets limits the scalability of available approaches. To overcome these challenges, and to facilitate the inference of lineage-specific GRNs with directed regulator-target relations, we introduce NetID. This approach optimizes coverage of the cell state manifold by homogenous metacells and avoids spurious gene-gene correlations observed with available imputation methods. Benchmarking demonstrates superior performance of NetID compared to imputation-based GRN inference. By incorporating cell fate probability information, NetID facilitates prediction of lineage-specific GRNs and recovers known network motifs centered around lineage-determining transcription factors governing bone marrow hematopoiesis, making it a powerful toolkit for deciphering the gene regulatory control of cellular differentiation from large-scale single-cell transcriptome data.
A can of worms: estimating the global number of earthworm species
Authors: Decaëns Thibaud , Brown George G. , Cameron Erin K. , Csuzdi Csaba , Eisenhauer Nico , Gérard Sylvain , Goulpeau Arnaud , Hedde Mickaël , James Samuel W. , Lapied Emmanuel , Maggia Marie-Eugénie , Marchán Daniel F. , Mathieu Jérôme , Phillips Helen R. P. , Marcon Eric 
Published: September 2024

AbstractEstimating the overall number of species for a given taxon is a central issue in ecology and conservation biology. It should be particularly topical in the case of soil organisms, which represent the majority of known species, but still suffer from a considerable taxonomic knowledge deficit. We propose here an estimation of the global number of earthworm species based on the Joppa approach, which models taxonomic effort over time in order to estimate the total number of known and as yet unknown species in a given taxa. Our Bayesian estimation of this model allows us to propose a global diversity of the order of 30,000 species. However, the uncertainty around this estimate is considerable due to severe undersampling and as the model cannot unambiguously decide whether we are describing few species because of a small pool of as yet unknown species, or because of a lack of taxonomic efficiency. This means that the 5,679 species and subspecies already described only represent around 20% of the global number of earthworm species. Considering the current rate of new species description, we calculate that it would take at least 120 years to describe all the species existing on Earth. We discuss the strategies that could be developed to reduce the magnitude of this taxonomic deficit.
ROBI: a Robust and Optimized Biomarker Identifier to increase the likelihood of discovering relevant radiomic features
Authors: Rebaud Louis , Capobianco Nicolò , Sarkozy Clémentine , Cottereau Anne-Ségolène , Vercellino Laetitia , Casasnovas Olivier , Thieblemont Catherine , Spottiswoode Bruce , Buvat Irène 
Published: September 2024

AbstractObjectivesThe Robust and Optimized Biomarker Identifier (ROBI) feature selection pipeline is introduced to improve the identification of informative biomarkers coding information not already captured by existing features. It aims to accurately maximize the number of discoveries while minimizing and estimating the number of false positives (FP) with an adjustable selection stringency.Methods500 synthetic datasets and retrospective data of 378 Diffuse Large B Cell Lymphoma (DLBCL) patients were used for validation. On the DLBCL data, two established radiomic biomarkers, TMTV and Dmax, were measured from the 18F-FDG PET/CT scans, and 10,000 random ones were generated. Selection was performed and verified on each dataset. The efficacy of ROBI has been compared to methods controlling for multiple testing and a Cox model with Elasticnet penalty.ResultsOn synthetic datasets, ROBI selected significantly more true positives (TP) than FP (p < 0.001), and for 99.3% of datasets, the number of FP was within the estimated 95% confidence interval. ROBI significantly increased the number of TP compared to usual feature selection methods (p < 0.001). On retrospective data, ROBI selected the two established biomarkers and one random biomarker and estimated 95% chance of selecting 0 or 1 FP and a probability of 0.0014 of selecting only FP. Bonferroni correction selected no feature, and Elasticnet selected 101 spurious features and discarded TMTV.ConclusionROBI selected relevant biomarkers while effectively controlling for FPs, outperforming conventional selection methods. This underscores its potential as a valuable asset for biomarker discovery.HighlightsROBI is a feature selection tool capable of screening thousands of features.It enables systematic evaluation of numerous radiomic features while minimizing false discoveries.ROBI was validated on synthetic and real datasets, outperforming other selection techniques.
Altered food liking in depression is driven by macronutrient composition
Authors: Thurn Lilly , Schulz Corinna , Borgmann Diba , Klaus Johannes , Ellinger Sabine , Walter Martin , Kroemer Nils B. 
Published: September 2024

AbstractMajor depressive disorder (MDD) is characterized by changes in appetite and body weight as well as blunted reward sensitivity (“anhedonia”). However, it is not well understood which mechanisms are driving changes in reward sensitivity, specifically regarding food. Here, we used a sample of 117 participants (54 patients with MDD; 63 healthy control participants, HCP) who completed a food cue reactivity (FCR) task with ratings of wanting and liking for 60 food and 20 non-food items. To evaluate which components of the food may contribute to altered ratings in depression, we tested for associations with macronutrients of the depicted items. In line with previous studies, we found reduced ratings of food wanting (p= .003), but not liking (p= .23) in patients with MDD compared to matched HCPs. Adding macronutrient composition to the models of wanting and liking substantially improved their fit (ps < .001). Compared to carbohydrate-rich foods, patients with MDD reported lower liking and wanting ratings for high-fat and high-protein foods. Moreover, patients with MDD showed weaker correlations in their preferences for carbohydrate-versus fat- or protein-rich foods (ps < .001), pointing to potential disturbances in metabolic signaling. To conclude, our results suggest that depression-related alterations in food reward ratings are more specific to the macronutrient composition of the food than previously anticipated, hinting at disturbances in gut-brain signaling. These findings raise the intriguing question whether interventions targeting the gut could help normalize aberrant reward signals for foods rich in fat or protein.Abstract Figure
Management of Dementia in a Resource-Constrained Sub-Saharan African Setting: Outcome of a Retrospective Survey of Clinical Practice in the Only Neuropsychiatric Facility in Northeastern Nigeria
Authors: Wakawa Ibrahim Abdu , Musami Umar Baba , Kwairanga Suleiman Hamidu , Ogualili Placidus Nwankuba , Mahmood Mohammed Yusuf , Fugu Muhammad Abba , Gimba Mohammed Mala , Allamin Muktar Mohammed , Abbas Zaharudeen Umar , Sunkani Muhammad Kawu , Yaganami Zainab Bukar , Kadau Fatima Mustapha , Sani Nasir Muhammad , Danmallam Peter , Nanjul Luka , Babazau Larema , Muhammad Zaid , Goni Baba Waru , Machina Babagana Kundi , Karch Celeste M. , Udeh-Momoh Chinedu , Karikari Thomas K. , Onyike Chiadi U. , Maina Mahmoud Bukar 
Published: September 2024

AbstractIntroductionDementia prevalence is rising in sub-Saharan Africa due to a combination of factors, including population growth and aging. In resource-constrained settings, such as Northeastern Nigeria, dementia management is challenged by delayed diagnosis and limited specialist care. This study evaluates the burden of dementia and its management at the Federal Neuropsychiatric Hospital Maiduguri (FNHM), the only neuropsychiatric facility in Northeastern Nigeria. The study aims to provide insights into current dementia trends and practices and identify key areas for improvement.MethodsA retrospective analysis of patient records at FNPH Maiduguri was conducted, including patients aged 60 and above diagnosed with dementia between 1999 and 2023. Data on patient demographics, dementia subtypes, comorbidities, symptoms, diagnostic investigations, and treatment modalities were analysed.ResultsThe Available record from the hospital health records register showed that the total number of diagnosed cases of dementia in the FNHM is 1,216 cases with a male predominance (56%). Alzheimer’s disease was the most common subtype (60.5%), followed by vascular dementia (24.5%). Hypertension was the most frequently reported comorbidity (41.6%). Cognitive symptoms, particularly memory loss, were reported in all cases, while behavioural symptoms, such as agitation and hallucinations, were reported in some cases. The most commonly administered treatments included cognitive enhancers (donepezil), supplements (gingko biloba), and non-drug therapies (psychoeducation). However, 70.9% of patients were lost to follow-up, highlighting a critical gap in long-term care.ConclusionThe increasing burden of dementia at the only neuropsychiatric facility in Northeastern Nigeria highlights the urgent need for investments and targeted interventions. Enhancing patient engagement, strengthening follow-up systems, and expanding diagnostic and treatment capacities will improve care outcomes and address the growing demands for dementia management in this underserved region.
The induction of dissociative states: A meta-analysis
Authors: Brake Benjamin , Wieder Lillian , Hughes Natasha , Saravia Lalinde Ivonne , Marr Danielle , Geagea Dali , Pick Susannah , Reinders Antje A. T. S. , Kamboj Sunjeev K. , Thompson Trevor , Terhune Devin B. 
Published: September 2024

AbstractObjectiveDissociative states, characterised by discontinuities in awareness and perception, occur in a diverse array of psychiatric disorders and contexts. Dissociative states have been modeled in the laboratory through various induction methods but relatively little is known about the efficacy and comparability of different experimental methods.MethodsThis meta-analysis quantified dissociative states, as indexed by a standardised instrument (Clinician Administered Dissociative States Scale), at baseline in varied diagnostic groups and in response to different experimental induction methods (psychological techniques and pharmacological agents) in both clinical and non-clinical samples. Primary outcomes were state dissociation effect sizes (Hedges’sg) (PROSPERO registration CRD42022384886).Results2,214 papers were screened, yielding 150 eligible articles and 251 effect sizes comprising 7,190 individuals. High levels of baseline state dissociation were observed in multiple diagnostic groups relative to controls, with the largest effects found in post-traumatic stress disorder (PTSD). In controlled experiments, induced state dissociation was most pronounced in response to mirror-gazing, ayahuasca, ketamine, cannabis, MDMA, and nitrous oxide relative, with effects comparable to or exceeding baseline state dissociation in PTSD. The effect sizes were characterised by pronounced heterogeneity but were not reliably associated with methodological features of the original studies.ConclusionsElevated state dissociation is present in multiple diagnostic groups and comparable or higher levels can be reliably induced in controlled experiments using psychological techniques and pharmacological agents. These results demonstrate the efficacy of several methods for experimentally modelling dissociation and have implications for measuring adverse events and predicting outcomes in clinical interventions involving pharmacological agents.
Use of Metagenomic Microbial Plasma Cell-Free DNA Next-Generation Sequencing Assay in Outpatient Rheumatology Practice
Authors: Jenkins Rachel , Samec Matthew , Arment Courtney , Warrington Kenneth J. , Davis John M. , Koster Matthew J. 
Published: September 2024

AbstractObjectivesTo assess the utility of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius TestTM; KT) in the evaluation of patients in an outpatient rheumatology practice.MethodsAll patients with a KT ordered and obtained by a rheumatology provider in the outpatient setting from 1 January 2020 through 31 December 2022 were retrospectively identified. Demographic, clinical, laboratory, radiologic, histopathology, and microbial studies were abstracted. Indication for KT testing was categorized. KT results were defined based on positive result and clinical relevance regarding the symptoms under investigation at the time of the rheumatologic investigation. Review of cases three months after KT was undertaken to determine clinical outcome.Results150 patients with a KT were included (53% female, mean age 52 years). The reason for KT was evaluation of atypical presentation of rheumatic disease (80%), assessing flare versus infection in patient on immunosuppression (16.7%), and fever of unknown origin (3.3%). 24 (16%) KTs were positive, 6 of which were considered clinically relevant and altered the final diagnosis and treatment. Of the 126 negative KTs, 5 (4%) were found to have a clinically relevant infection by conventional testing methodologies.ConclusionsIn this large retrospective cohort study, the most frequent reason for KT utilization was an atypical presentation of rheumatic disease. 25% of positive KTs altered the final diagnosis and treatment, whereas a false-negative rate of 4% was observed. KT has utility in the outpatient rheumatology assessment. Further delineation of which patients are best suited for KT testing remains to be defined.Key messagesUse of microbial cell free DNA testing assisted in differentiating between atypical infection and rheumatologic presentationFurther studies are needed to define the most optimal patient selection for maximizing mcfDNA technologies in the rheumatology outpatient setting
Adverse Events During a 12-month Multi-Site and Dose-Response Aerobic Exercise Intervention
Authors: Vidoni Eric D. , Grove George , Szabo-Reed Amanda N. , Key Mickeal N. , Huang Haiqing , Burns Jeffrey M. , Hillman Charles H. , Jakicic John M. , Kang Chaeryon , Kramer Arthur F. , McAuley Edward , Wan Lu , Hawes Tera , White Sydney S. , Erickson Kirk I. 
Published: September 2024

ABSTRACTPurposeThis study aimed to assess the incidence of adverse events (AE) in older adults participating in a year-long exercise intervention, investigating potential dose-response relationships between exercise intensity and AE frequency, and identifying demographic factors associated with AE risk.MethodsA total of 648 older adults were randomized into one of three exercise groups: low-intensity stretching and toning (S&T), 150 minutes of aerobic exercise per week (150Ex), or 225 minutes of aerobic exercise per week (225Ex). Adverse events were tracked during the intervention, with event rates calculated based on participant adherence and time in the study. Generalized linear models were employed to compare AE incidence across groups. Post hoc comparisons were used to calculate incidence rate ratios (IRRs) for AE between groups, adjusting for multiple comparisons.ResultsOverall, 306 AE were reported, with 44% related to the intervention. No significant dose-response relationship was observed for all-cause AE between groups. However, intervention-related AE were more frequent in the aerobic exercise groups. Participants in the 150Ex group had a 77% higher rate of intervention-related AE compared to the S&T group, and the 225Ex group had an 88% higher rate. Higher adherence was associated with fewer all-cause AE, and greater comorbid burden was associated with more AE.ConclusionsWhile aerobic exercise increased the risk of intervention-related AE, the overall risk remained low. Higher adherence to the exercise regimen was associated with fewer AE. These findings suggest aerobic exercise is generally safe in older adults, with the benefits outweighing the risks.
Deciphering TB-IRIS in HIV Patients: A Comprehensive Clinical and Microbiological Analysis
Authors: Gupta Priyanka , Tripathi Anil Kumar , Singh Kaleshwar Prasad , Jain Amita , Gupta Abhishek 
Published: September 2024

AbstractBackgroundTuberculosis (TB) and Human Immunodeficiency Virus (HIV) coinfection presents a complex clinical challenge, with Tuberculosis-Immune Reconstitution Inflammatory Syndrome (TB-IRIS) emerging as a significant complication following antiretroviral therapy (ART) initiation. Understanding the clinical and microbiological characteristics of TB-IRIS is crucial for improving patient outcomes.MethodsThis prospective cohort study included 400 HIV-positive patients from the ART centre at King George’s Medical University, Lucknow, India. Patients were categorized based on TB status and monitored for the development of TB-IRIS following ART initiation. Clinical data, CD4 counts, and microbiological analyses, including drug susceptibility testing, were conducted. TB-IRIS was classified as paradoxical or unmasking, and outcomes were assessed over a one-year period.ResultsAmong the 400 patients, 38 (9.5%) developed TB-IRIS, with 31 (81.6%) presenting unmasking TB-IRIS and 7 (18.4%) paradoxical TB-IRIS. Tubercular meningitis (TBM) was the most common manifestation (47.3%), followed by pulmonary TB (29.0%). The incidence of TB-IRIS was higher (15.4%) in patients who initiated ART within one month of starting anti-tuberculosis therapy (ATT) compared to those who started ART later (5.5%). A lower baseline CD4 count (<100 cells/µL) was significantly associated with a higher risk of TB-IRIS (p=0.003). The drug resistance analysis revealed 27.2% resistance to both isoniazid and rifampicin. Steroid therapy was administered to 13% of TB-IRIS patients. The overall cure/improvement rate was 71%, while the mortality rate was 23.6%. No patients discontinued ART during the study.ConclusionThis study highlights the predominance of unmasking TB-IRIS in HIV patients initiating ART, particularly those with low baseline CD4 counts and early ART initiation post-ATT. The significant drug resistance observed underscores the need for robust diagnostic and treatment protocols. Improved management strategies are essential to enhance clinical outcomes in TB-IRIS patients.