bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD Suggest Age Mediates Subtypes of ASD
Authors: Ressa Haylee J. , Newman Benjamin T. , Jacokes Zachary , McPartland James C. , Kleinhans Natalia M. , Druzgal T. Jason , Pelphrey Kevin A. , Van Horn John Darrell ,   GENDAAR Research Consortium
Published: September 2024

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, this study aims to first associate a broad array of behavioral metrics with neuroimaging markers of ASD, and to explore the prevalence of ASD subtypes using a neuroimaging driven perspective. Analyzing 273 participants (148 with ASD) ages 8 to 17 through an NIH-sponsored Autism Centers of Excellence network (MH100028), we observe widespread associations between behavioral and cognitive evaluations of autism and between behavioral and microstructural metrics, alongside different directional correlations between different behavioral metrics. Stronger associations with individual subcategories from each test rather than summary scores suggest that different neuronal profiles may be masked by composite test scores. Machine learning cluster analyses applied to neuroimaging data reinforce the association between neuroimaging and behavioral metrics and suggest that age-related maturation of brain metrics may drive changes in ASD behavior. This suggests that if ASD can be definitively subtyped, these subtypes may show different behavioral trajectories across the developmental period. Clustering identified a pattern of restrictive and repetitive behavior in some participants and a second group that was defined by high sensory sensitivity and language performance.
Shifting Routes: Plant Specific Insert trafficking and function in Arabidopsis seedlings under abiotic stress
Authors: Moura Inês , Neves João , Séneca Ana , Pissarra José , Pereira Susana , Pereira Cláudia 
Published: September 2024

AbstractDue to plants’ inability to escape adverse conditions, they must adapt and adjust their endomembrane system through protein sorting and distribution. Cardosins A and B are key models for studying intracellular trafficking. They are aspartic proteinases in thistle flowers that mediate different vacuolar pathways despite sharing high sequence similarity, and both are responsive to stress conditions. The Plant Specific Insert (PSI) is a 100 amino acid domain found in these proteins. It is known that stress can impact protein sorting, shifting it from the conventional pathway (ER-Golgi) to a Golgi-independent route. In this work we assessed changes in the expression and localization of PSI from Cardosin B (PSI B) in Arabidopsis plants overexpressing PSI B-mCherry submitted to different abiotic stress conditions (saline, hydric, oxidative, metals). Aside from potential PSI B localization changes, we focused on characterizing the homozygous line, alongside assessing several biometric parameters and biochemical endpoints. The results revealed that the PSI B line responded differently depending on the stress conditions. Biometric and biochemical analyses emphasized the roles of PSI B in enhancing plant fitness and supporting adaptation to abiotic stress. Besides, confocal microscopy allowed us to find PSI B accumulation in Endoplasmic Reticulum-derived vesicles (ER bodies), indicating a shift from the common PSI B-mediated route. These findings underscore the role of PSI B in enhancing plant fitness and adaptation to abiotic stress through altered protein trafficking.HighlightPSI B has an active role in enhancing plant fitness, revealing its value in adaptation and tolerance to abiotic stress by adjusting its localization and trafficking under challenging environments.
Comprehensive analysis of the RBP regulome reveals functional modules and drug candidates in liver cancer
Authors: Garbulowski Mateusz , Mosca Riccardo , Gallardo-Dodd Carlos J. , Kutter Claudia , Sonnhammer Erik L. L. 
Published: September 2024

AbstractRNA binding proteins (RBPs) are essential components of the transcriptomic regulome. Identifying the RBP regulome in cancer cells is crucial to discovering and understanding carcinogenesis mechanisms and providing new therapeutic targets. Here, we aimed to reveal the regulome of liver cancer upon specific perturbations. To this end, we applied a consensus Gene Regulatory Network (GRN) approach using knockdown data for the liver cancer cell line HepG2. By incorporating multiple GRNs from diverse inference methods, we constructed a highly precise GRN. To validate our results, we comprehensively evaluated the consensus GRN, focusing on characterizing the most relevant aspects of the liver cancer regulome. This included utilizing eCLIP-seq and RAPseq data to verify RBP interactions and binding sites. In addition, we performed an enrichment analysis of network modules and drug repurposing based on the inferred GRN. Taken together, our findings demonstrate the critical roles of RBP regulatory interactions in liver cancer that can be employed to improve treatment strategies.
The phospho-ferrozine assay: A tool to study bacterial redox-active metabolites produced at the plant root
Authors: Giacalone David , Schutt Emilly , McRose Darcy L. 
Published: September 2024

AbstractSoil microbial communities are pivotal to plant health and nutrient acquisition. It is becoming increasingly clear that many interactions, both among and between microbes and plants, are governed by small bioactive molecules or “secondary metabolites” that can aid in communication, competition, and nutrient uptake. Yet, secondary metabolite biogeography – who makes what, where, and why— is in its infancy. Further, secondary metabolite biosynthesis genes are often silent or weakly expressed under standard laboratory conditions, making it incredibly difficult to study these small molecules. To begin to address these dual challenges, we focused on Redox-Active metabolites (RAMs), a specific class of small molecules, and took advantage of recent findings that many RAMs aid in acquiring phosphorus and that their production is frequently stimulated by stress for this macronutrient. We developed a screen for RAM-producing bacteria that leverages phosphorus limitation to stimulate metabolite biosynthesis and uses a colorimetric (ferrozine) iron-reduction assay to identify redox activity. We isolated 557 root-associated bacteria from grasses collected at sites across the United States (Santa Rita Experimental Range (AZ), Konza Prairie Biological Station (KS), and Harvard Forest (MA)) and from commercial tomato plants and screened them for RAM production. We identified 128 soil isolates of at least 19 genera across Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes that produced RAMs under phosphorus stress. Our work reveals that the production of RAMs under phosphorus stress is common across diverse soil bacteria and provides an approach to screen for these small molecules rapidly.ImportanceBy secreting secondary metabolites, bacteria at the plant root can defend against diseases and help acquire essential nutrients. However, the genes which synthesize secondary metabolites are typically inactive or are weakly expressed under standard laboratory conditions. This fact makes it difficult to study these small molecules and hinders the discovery of novel small molecules that may play crucial roles in agricultural and biomedical settings. Here, we focus on Redox-Active metabolites (RAMs), a class of secondary metabolites that can help bacteria solubilize phosphorus and are often produced when phosphorus is limited. We developed a screen that rapidly identifies RAM-producing bacteria by utilizing a colorimetric iron-reduction assay in combination with phosphorus limitation to stimulate biosynthesis. The screen reveals that RAM-producing bacteria are far more prevalent in soil than previously appreciated and that this approach can be used to identify RAM producers.
Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism with and without Profound Impairment: An Observational Study
Authors: Smith Joshua Ryan , Lim Seri , Bindra Snehal , Marler Sarah , Rajah Bavani , Williams Zachary J. , Baldwin Isaac , Hossain Nausheen , Wilson Jo Ellen , Fuchs D. Catherine , Luccarelli James 
Published: September 2024

AbstractIntroductionCatatonia is a highly morbid psychomotor and affective disorder which can affect autistic individuals with and without profound impairment. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments has not been described.MethodsWe conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1st, 2021 to May 31st, 2024. Data investigating pharmacologic interventions, and clinical measures including the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), Kanner Catatonia Examination (KCE), and Clinical Global Impression – Improvement (CGI-I) were collected.ResultsForty-five patients were identified with 39 (86.7%) meeting criteria for profound autism. All patients received pharmacotherapy. 44 (97.8%) were treated with benzodiazepines with a mean maximal daily dose of 17.4 mg (SD=15.8) lorazepam equivalents. Thirty-five patients (77.8%) required more than one medication class for treatment. Fourteen patients (31.1%) attempted to taper off benzodiazepines during the study period; of these, 5 patients (11.1%) were successfully tapered off, and the remaining 9 (17.8%) discontinued the taper due to a return of catatonic symptoms. Statistically significant improvement was observed across all clinical domains except the KCS. However, the majority remained symptomatic over the study period.ConclusionsDespite clinical improvements while receiving the gold standard for psychopharmacologic management of catatonia, chronic symptoms remained for the majority of catatonia patients over the study period, and few were able to taper and discontinue benzodiazepine treatment.Lay SummaryCatatonia is a condition which can significantly impact the quality of life for autistic individuals with and without profound impairment. Symptoms of catatonia such as aggression and self-injury can improve with treatment. However, over the three-year period of this study, most patients experienced residual symptoms, and few could discontinue psychotropic medication.
Comparison of haemoglobin concentration measurements using HemoCue-301 and Sysmex XN-Series 1500: a survey among anaemic Gambian infants aged 6-12 months
Authors: Bah Mamadou , Verhoef Hans , Camara Abdou , Ngom Morris Nden , Jallow Demba , Bajo Kebba , Bah Foday , Pleij Maarten , Klappe Maaike , Saidykhan Alasana , Okoh Emmanuel , Bah Abdoulie , Cerami Carla 
Published: September 2024

ABSTRACTBackground & AimsIn low-income countries, point-of-care photometers are used in the screening and management of anaemia in individuals, but also in the assessment of population iron status when evaluating efficacy of intervention studies or public health interventions. We aimed to evaluate the accuracy of a commonly used photometer, HemoCue-301, in determining haemoglobin concentration among anaemic children aged 6-12 months in a field setting in rural Africa.MethodsThis report concerns a secondary analysis of data from Gambian infants being screened for an ongoing randomized controlled trial. In those found to be anaemic by HemoCue-301, haemoglobin concentration was measured by Sysmex XN-1500, an automated haematology analyser that was used as a reference. Passing-Bablok regression analysis was used to estimate the regression constant (systematic deviation between two measurement methods that remain consistent across the range of measurements) and proportional bias (systematic deviation between two measurement methods that change in magnitude relative to the value being measured).ResultsAnalysis was based on 227 participants. There was strong evidence of absolute bias among moderately anaemic participants (haemoglobin concentration at 8.0g/dL) (absolute bias: 1.12g/dL; 95% CI: 0.91 to 1.37g/dL; proportional bias: 14.0%; 95% CI: 11.4% to 17.1%) in haemoglobin concentrations measured by HemoCue-301 compared to those measured by Sysmex XN-Series1500. Bias was marginal at haemoglobin concentration of 11.0g/dL (absolute bias: −0.08g/dL; 95% CI: −0.18 to 0.07g/dL; proportional bias: −7.3%; 95% CI: −6.5% to 0.6%).ConclusionHaemoglobin measurements by HemoCue-301 seem substantially biased in participants with haemoglobin less than 8.0g/dL.
Online group-based Acceptance and Commitment Therapy for stroke survivors: a study of fidelity of delivery within the Wellbeing After Stroke study
Authors: Foote Hannah , Bowen Audrey , Cotterill Sarah , Patchwood Emma 
Published: September 2024

AbstractObjectivesTo explore whether practitioners can deliver the Acceptance and Commitment Therapy-based Wellbeing After Stroke intervention with fidelity to both the clinical protocol and the Acceptance and Commitment therapy model.DesignObservational fidelity study, embedded within the Wellbeing After Stroke study. Setting: online groups. UK.ParticipantsPractitioners employed by the Stroke Association, trained to deliver the intervention.Measures1) a bespoke Wellbeing After Stroke fidelity tool to assess fidelity to dose, duration and content of intervention sessions, self-completed by practitioners and a sub-set completed by researchers based on video recordings. We calculated inter-rater reliability of researchers and practitioners. 2) Acceptance and Commitment Therapy-Fidelity Measure to assess fidelity to the Acceptance and Commitment Therapy model, completed by researchers on the sub-set of recorded sessions.ResultsSeven practitioners delivered the Wellbeing After Stroke intervention to three groups of stroke survivors. The planned dose of the intervention was delivered, with duration slightly longer than planned. Practitioners delivered the intervention with high fidelity to protocol: 92–100% of content delivered, as measured by the Wellbeing After Stroke fidelity tool, once reliability was established. Some practitioners delivered the intervention with fidelity to the Acceptance and Commitment Therapy model.ConclusionsTrained and supervised practitioners can deliver an online, group Acceptance and Commitment Therapy-based intervention to stroke survivors with high fidelity to protocol. Improving training may increase consistency with the Acceptance and Commitment Therapy model. The ACT-Fidelity Measure can be used to measure consistency of delivery of protocolised, group interventions, but adaptations would increase suitability to context.
Evaluating the Risk of Cardiovascular Adverse Events and Appendicitis After COVID-19 Diagnosis in Adults in the United States: Implications of the Start of Follow-Up
Authors: Layton J. Bradley , Lindaas Arnstein , Muthuri Stella G , Lloyd Patricia C. , Richey Morgan M. , Gruber Joann F. , Lyu Hai , McKillop Mollie M. , Kowarski Lisa S. , Bui Christine , Fisher Shelby S. , Clarke Tainya C. , Cheng Angela S. , Wan Zhiruo , Duenas Pablo Freyria , Chen Yangping , Burrell Timothy , Sheng Minya , Shoaibi Azadeh , Chillarige Yoganand , Beers Jeffrey , Anthony Mary S. , Forshee Richard A. , Anderson Steven A. 
Published: September 2024

AbstractPurposeThis study evaluated the association between coronavirus disease 2019 (COVID-19) diagnosis and adverse events (AEs), including cardiovascular AEs and appendicitis, in US adults before the introduction of COVID-19 vaccines. Real-world studies of AEs after COVID-19 suggest that diagnoses of AEs and COVID-19 frequently occur on the same day and may be a source of bias.MethodsCohort and self-controlled risk interval (SCRI) designs were used in 2 US administrative claims data sources—Merative™ MarketScan® (ages 18-64 years) and Medicare (ages ≥ 65 years). AEs included stroke (nonhemorrhagic and hemorrhagic), acute myocardial infarction, myocarditis/pericarditis, deep vein thrombosis, pulmonary embolism (PE), disseminated intravascular coagulation (DIC), unusual-site and common-site thrombosis with thrombocytopenia syndrome, and appendicitis. In cohort analyses, weighted hazard ratios (HRs) and 95% confidence intervals (CIs) compared adults with a COVID-19 diagnosis and matched comparators. In SCRI analysis, relative incidences (RIs) and 95% CIs compared risk and reference windows within individuals. Analyses were performed starting follow-up on Time 0 and Day 1.ResultsFor cardiovascular AEs, all estimates starting follow-up on Day 1 were above 1.0 in both data sources. For cohort analyses, the strongest associations were for inpatient PE in both databases: MarketScan, HR=8.65 (95% CI, 6.06-12.35), Medicare HR=3.06 (95% CI, 2.88-3.26). For SCRI analyses, the strongest association in MarketScan was for DIC: RI=32.28 (95% CI, 17.06-61.09) and in Medicare was for myocarditis/pericarditis: RI=4.53 (95% CI, 3.89-5.27). AEs diagnosed concurrently with COVID-19 (ie, on Time 0) were common; including Time 0 in follow-up/risk windows resulted in higher RIs, as well as higher HRs for some AEs. However, some AEs (eg, stroke) were more common on Time 0 in the comparator group resulting in lower HRs.ConclusionCOVID-19 diagnoses had moderate to strong associations with cardiovascular AEs and weak or inconsistent associations with appendicitis, although estimates varied by design and methodology.
Integration of GWAS and multi-omic QTLs identifies uncharacterized COVID-19 gene-biotype and phenotype associations
Authors: Oliva Meritxell , King Emily , Hammond Reza , Lee John S. , Riley-Gillis Bridget , Resztak Justyna , Degner Jacob 
Published: September 2024

AbstractTo better understand COVID-19 pathobiology and to prioritize treatment targets, we sought to identify human genes influencing genetically driven disease risk and severity, and to identify additional organismal-level phenotypes impacted by pleiotropic COVID-19-associated genomic loci. To this end, we performed ancestry-aware, trans-layer, multi-omic analyses by integrating recent COVID-19 Host Genetics Initiative genome-wide association (GWAS) data from six ancestry endpoints - African, Amerindian, South Asian, East Asian, European and meta-ancestry - with quantitative trait loci (QTL) and GWAS endpoints by colocalization analyses. We identified colocalizations for 47 COVID-19 loci with 307 GWAS trait endpoints and observed a highly variable (1-435 endpoint colocalizations) degree of pleiotropy per COVID-19 locus but a high representation of pulmonary traits. For those, directionality of effect mapped to COVID-19 pathological alleles pinpoints to systematic protective effects for COPD, detrimental effects for lung adenocarcinoma, and locus-dependent effects for IPF. Among 64 QTL-COVID-19 colocalized loci, we identified associations with most reported (47/53) and half of unreported (19/38) COVID-19-associated loci, including 9 loci identified in non-European cohorts. We generated colocalization evidence metrics and visualization tools, and integrated pulmonary-specific QTL signal, to aid the identification of putative causal genes and pulmonary cells. For example, among likely causal genes not previously linked to COVID-19, we identified desmoplakin-driven IPF-shared genetic perturbations in alveolar cells. Altogether, we provide insights into COVID-19 biology by identifying molecular and phenotype links to the genetic architecture of COVID-19 risk and severity phenotypes; further characterizing previously reported loci and providing novel insights for uncharacterized loci.
Public Health Interventions for Fractional Optimal Control of Buruli Ulcer
Authors: Nortey Solomon , Akorly Ernest , Dadzie Mark , Moore Stephen E. 
Published: September 2024

AbstractBuruli Ulcer, a devastating skin disease caused byMycobacterium Ulcerans, poses considerable public health challenges in endemic areas. This article focuses on the use of fractional optimal control theory to prevent the spread of Buruli ulcers via integrated public health interventions. We formulated a mathematical model using the Atangana-Baleanu-Caputo fractional order derivative operator. We investigated the model’s existence and uniqueness and presented numerical simulations using the predict-evaluate-correct-evaluate (PECE) method of Adam-Bashforth Moulton. We also study the fractional optimal control problem (FOCP) to minimize the spread of the disease in the endemic regions. We employ the Fractional Pontryagin’s Maximum Principle (FPMP) and implement the forward-backward method to determine the extremals of the problem. Four control strategies were implemented: promoting health education on the use of protective clothing, enhancing vaccination rates, improving treatment protocols for infected individuals, and spraying insecticides to reduce water-bug populations. After examining the optimal control dynamics of the Buruli ulcer transmission model via multiple simulations with and without control, we discover that there is a substantial decrease in the population of infected humans and the water-bug population. Hence we conclude that the best strategy to implement is by applying all the control strategies suggested.
Off-purpose activity of industrial and agricultural chemicals against human gut bacteria
Authors: Lindell Anna E. , Kamrad Stephan , Roux Indra , Krishna Shagun , Grießhammer Anne , Smith Tom , Guan Rui , Rad Deniz , Faria Luisa , Blasche Sonja , Kleinstreuer Nicole C. , Maier Lisa , Patil Kiran R. 
Published: September 2024

AbstractContamination by industrial and agricultural chemicals like pesticides are a cause of great concern due to the risk to human and environmental health. While these chemicals are often considered to have restricted activity and are labelled as such, there are concerns over a broader toxicity range. Here we report the impact of 1076 pollutants spanning diverse chemistries and indicated applications on 22 prevalent commensal gut bacteria. Our systematic investigation uncovered 588 interactions involving 168 chemicals, the majority of which were not previously reported to have antibacterial properties. Fungicides and industrial chemicals showed the largest impact with circa 30% exhibiting anti-commensal properties. We find that the sensitivity to chemical pollutants across species surprisingly correlates with that to human-targeted drugs, suggesting common susceptibility mechanisms. Using a genome-wide chemical-genetic screen, we identified membrane transport and fatty acid metabolism as major modulators of the off-target toxicity of chemicals. Mutants exhibiting chemical resistance include those defective in producing human-health-relevant metabolites like branched short-chain fatty acids, indicating that chronic exposure could lead to selection against production of beneficial metabolites. Toxicokinetic modelling suggested gut bacteria could be used as more sensitivein vitrotoxicity indicators for chemicals of concern than animal models. Together, our data uncovers the off-target activity of industrial and agricultural chemicals with widespread exposure against human gut bacteria. Impact on the structure and function of the microbiota should therefore be considered in assessing chemical safety.