bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival, Movement, and Lifespan: Decoding the Roles ofPatched-Related(Ptr) inDrosophila melanogaster
Authors: Parada Cristina , Prieto Daniel 
Published: May 2024

AbstractPatched-related (Ptr) is a transmembrane protein implicated in developmental processes inDrosophila melanogaster, yet its precise role remains incompletely understood. Here, we usePtr23cnull mutants to investigate the functional significance of Ptr through the entire life cycle monitoring survival during embryonic, larval, pupal and adult development, and studying larval locomotion and muscle structure. We report thatPtr23clarvae displayed impaired hatching, indicative of defective embryonic development. Moreover, mutant larvae exhibited reduced mobility and lethargy, suggesting a potential involvement of Ptr in neuromuscular function. Morphological analysis of somatic muscles in mutant larvae revealed enlarged cell nuclei. Despite high pre-adult mortality, a subset ofPtr23cmutant adults display an unexpected extension in lifespan compared to controls, implicating Ptr in the regulation of longevity. Our findings provide critical insights into the multifaceted role of Ptr inDrosophiladevelopment, highlighting its contributions to post-embryonic survival, neuromuscular function, and lifespan regulation. This study underscores the significance of exploring broader genetic networks to unravel the complexities of developmental processes.Highlights-Loss of Ptr elicits impaired embryonic hatching, reduced mobility, and lethargy.-Ptr23c mutants display nuclear enlargement in somatic muscles.-Ptr23c individuals that survive to adulthood demonstrate extended longevity.
Effect of interhemispheric zero-phase entrainment of the intrinsic mu-rhythm on behavioral and neural markers of predictive coding
Authors: Heise Kirstin-Friederike , Albouy Geneviève , Dolfen Nina , Peeters Ronald , Mantini Dante , Swinnen Stephan P. 
Published: May 2024

AbstractGoal-directed behavior requires the integration of information from the outside world and internal (somatosensory) sources about our own actions. Expectations (or ‘internal models’) are generated from prior knowledge and constantly updated based on sensory feedback. This optimized information integration (’predictive coding’) results in a global behavioral advantage of anticipated action in the presence of uncertainty. Our goal was to probe the effect of phase entrainment of the sensorimotor mu-rhythm on visuomotor integration. Participants received transcranial alternating current stimulation over bilateral motor cortices (M1) while performing a visually-guided force adjustment task during functional magnetic resonance imaging. Inter-hemispheric zero-phase entrainment resulted in effector-specific modulation of performance precision and effector-generic minimization of force signal complexity paralleled by BOLD activation changes in bilateral caudate and increased functional connectivity between the right M1 and contralateral putamen, inferior parietal, and medial temporal regions. While effector-specific changes in performance precision were associated with contralateral caudate and hippocampal activation decreases, only the global reduction in force signal complexity was associated with increased functional M1 connectivity with bilateral striatal regions. We propose that zero-phase synchronization represents a neural mode of optimized information integration related to internal model updating within the recursive perception-action continuum associated with predictive coding.
Artesunate, EDTA and colistin work synergistically against MCR-negative and -positive colistin-resistantSalmonella
Authors: Zhai Yajun , Liu Peiyi , Hu Xueqin , Fan Changjian , Cui Xiaodie , He Qibiao , He Dandan , Ma Xiaoyuan , Hu Gongzheng , Zhai Yajun 
Published: May 2024

AbstractDiscovering new strategies to combat the multi-drug resistance bacteria constitutes a major medical challenge of our time. Previously, artesunate (AS) has been reported to exert antibacterial enhancement activity in combination with β-lactam antibiotics, via inhibition of the efflux pump AcrB. However, combination of AS and colistin (COL) revealed weak synergistic effect against a limited number of strains, and few studies have further explored its possible mechanism of synergistic action. In this paper, we found that AS and EDTA could strikingly enhance the antibacterial effects of COL againstmcr-1-andmcr-1+Salmonellastrains eitherin vitroorin vivo, when used in triple combination. The excellent bacteriostatic effect was primarily related to the increased cell membrane damage, accumulation of toxic compounds and inhibition of MCR-1. The potential binding sites of AS to MCR-1 (THR283, SER284, and TYR287) were critical for its inhibition of MCR-1 activity. Additionally, we also demonstrated that the CheA of chemosensory system and virulence-related protein SpvD were critical for the bacteriostatic synergistic effects of the triple combination. Selectively targeting CheA, SpvD or MCR using the natural compound AS could be further investigated as an attractive strategy for treatment ofSalmonellainfection. Collectively, our work opens new avenues towards the potentiation of COL and revealed an alternative drug combination strategy to overcome COL resistant bacterial infections.
Endothelial deletion ofp53generates transitional endothelial cells and improves lung development during neonatal hyperoxia
Authors: Ellis Lisandra Vila , Bywaters Jonathan D , Chen Jichao 
Published: May 2024

ABSTRACTBronchopulmonary dysplasia (BPD), a prevalent and chronic lung disease affecting premature newborns, results in vascular rarefaction and alveolar simplification. Although the vasculature has been recognized as a main player in this disease, the recently found capillary heterogeneity and cellular dynamics of endothelial subpopulations in BPD remain unclear. Here, we show Cap2 cells are damaged during neonatal hyperoxic injury, leading to their replacement by Cap1 cells which, in turn, significantly decline. Single-cell RNA-seq identifies the activation of numerous p53 target genes in endothelial cells, includingCdkn1a (p21). While global deletion ofp53results in worsened vasculature, endothelial-specific deletion ofp53reverses the vascular phenotype and improves alveolar simplification during hyperoxia. This recovery is associated with the emergence of a transitional EC state, enriched for oxidative stress response genes and growth factors. These findings implicate the p53 pathway in EC type transition during injury-repair and highlights the endothelial contributions to BPD.
Exercising with virtual reality is potentially better for the working memory and positive mood than cycling alone
Authors: Ochi Genta , Ohno Ken , Kuwamizu Ryuta , Yamashiro Koya , Fujimoto Tomomi , Ikarashi Koyuki , Kodama Naoki , Onishi Hideaki , Sato Daisuke 
Published: May 2024

AbstractAlthough virtual reality (VR) exercise has attracted attention as a factor in exercise habituation due to its mood-enhancing effects, its impact on brain function remains unclear. This study, involving 23 healthy university students, used functional magnetic resonance imaging (fMRI) to explore how VR exercise affects working memory, a key executive function, and its underlying neural mechanisms. Our findings indicate that a 10-min VR exercise session improved mood (arousal and vitality level) and working memory task performance (3-back task) more effectively than exercise or rest alone. Furthermore, the results confirmed that increased vitality from exercise and VR exercise interventions was associated with improved 3-back task performance. However, specific brain regions contributing to this enhancement remain unidentified. These results highlight VR exercise as the optimal exercise program for enhancing working memory function by increasing vitality level. These insights underscore VR’s potential as a novel exercise modality with benefits extending beyond exercise adherence to potentially preventing dementia and depression.
α-Synuclein Conformations in Plasma Distinguish Parkinson’s Disease from Dementia with Lewy Bodies
Authors: Kannarkat George T. , Zack Rebecca , Skrinak R. Tyler , Morley James F. , Davila-Rivera Roseanne , Arezoumandan Sanaz , Dorfmann Katherine , Luk Kelvin , Wolk David A. , Weintraub Daniel , Tropea Thomas F. , Lee Edward B. , Xie Sharon X. , Chandrasekaran Ganesh , Lee Virginia M.-Y. , Irwin David , Akhtar Rizwan S. , Chen-Plotkin Alice S. 
Published: May 2024

AbstractSpread and aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). While evidence exists for multiple aSyn protein conformations, often termed “strains” for their distinct biological properties, it is unclear whether PD and DLB result from aSyn strain differences, and biomarkers that differentiate PD and DLB are lacking. Moreover, while pathological forms of aSyn have been detected outside the brain (e.g.,in skin, gut, blood), the functional significance of these peripheral aSyn species is unclear. Here, we developed assays using monoclonal antibodies selective for two different aSyn species generatedin vitro– termed Strain A and Strain B – and used them to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma, through immunohistochemistry, enzyme-linked immunoassay, and immunoblotting. Surprisingly, we found that plasma aSyn species detected by these antibodies differentiated individuals with PD vs. DLB in a discovery cohort (UPenn, n=235, AUC 0.83) and a multi-site replication cohort (Parkinson’s Disease Biomarker Program, or PDBP, n=200, AUC 0.72). aSyn plasma species detected by the Strain A antibody also predicted rate of cognitive decline in PD. We found no evidence for aSyn strains in CSF, and ability to template aSyn fibrillization differed for species isolated from plasma vs. brain, and in PD vs. DLB. Taken together, our findings suggest that aSyn conformational differences may impact clinical presentation and cortical spread of pathological aSyn. Moreover, the enrichment of these aSyn strains in plasma implicates a non-central nervous system source.
Prefrontal 5α-reductase 2 mediates male-specific acute stress response
Authors: Cadeddu Roberto , Braccagni Giulia , Floris Gabriele , Branca Caterina , Corridori Eleonora , Salviati Sara , Sánchez Pilar , Santovito Luca Spiro , Torres Jesus M , Ortega Esperanza , Pinna Graziano , Moos Philip J. , Scheggi Simona , Bortolato Marco 
Published: May 2024

ABSTRACTA key response to acute stress is the increased brain synthesis of the neurosteroid allopregnanolone (AP). While the rate-limiting step of this reaction is catalyzed by 5α-reductase (5αR), the role of its two primary isoenzymes, 5αR1 and 5αR2, in stress reactivity remains unclear. Here, we found that acute stress led to increased levels of 5αR2, but not 5αR1, in the medial prefrontal cortex (mPFC) of male, but not female, rats. Downregulation of 5αR2 in the mPFC significantly reduced stress response in males, and similar sexual dimorphic effects were observed in a novel line of 5αR2 knockout rats. Notably, 5αR1 regulated baseline AP synthesis, while 5αR2 enabled AP production under stress. Acute AP administration restored stress response in 5αR2 knockdown rats. Single-nucleus transcriptomics showed that 5αR2 enabled stress-induced protein translation in neurons and glia. These results highlight the crucial role of 5αR2 in mediating sex-specific differences in acute stress reactivity.
Wearable neuroprosthesis improves mobility and reduces pain in neuropathic participants
Authors: Gozzi Noemi , Chee Lauren , Odermatt Ingrid , Kikkert Sanne , Preatoni Greta , Valle Giacomo , Pfender Nikolai , Beuschlein Felix , Wenderoth Nicole , Zipser Carl , Raspopovic Stanisa 
Published: May 2024

AbstractPeripheral neuropathy (PN) is the most common complication of diabetes. It is characterized by sensory loss which often causes major health consequences including foot ulceration, chronic pain, poor mobility and increased risk of falls. However, present treatments do not counteract the cause of the disease, namely lack of sensory feedback, but rather aim at partial and temporal symptoms relief (e.g. analgesics for pain or creams for ulcers healing). Electrical stimulation is a promising solution for sensory restoration, but it is yet unknown if it can elicit perceivable sensations in PN damaged nerves and whether it could lead to any health or functional benefits. To this aim, we designed a wearable sensory neuroprosthesis providing targeted neurostimulation at the ankle level (NeuroStep) restoring feet lost sensations. We tested it in 14 participants with PN, evaluating its effects on functional outcomes and pain, and the cortical activation related to the restored sensations. Our system was able to restore lost sensations in all participants. The nerves of PN participants resulted significantly less excitable and sensitive than healthy individuals (N=22). Thanks to the neurostimulation, participants improved cadence and functional gait, with even stronger improvements in individuals with higher risk of falls. A full day of NeuroStep use led to a clinically significant reduction of 30.4% ± 9.2% in neuropathic pain. Restored sensations activated cortical patterns, as measured via fMRI, similar to the naturally located foot sensations, thus not requiring training by the user. NeuroStep restores intuitive sensations in PN participants, improving mobility and decreasing pain, possibly replacing multiple inefficient treatments. It holds potential to drastically improve patients’ quality of life thanks to functional and health benefits, while paving the way to new effective neuromodulation treatments.
Occupation Recognition and Exploitation in Rheumatology Clinical Notes: Employing Deep Learning Models for Named Entity Recognition and Knowledge Discovery in Electronic Health Records
Authors: Madrid-García Alfredo , Pérez-Sancristóbal Inés , Leticia-Leon  , Lydia-Abásolo  , Fernández-Gutiérrez Benjamín , Rodríguez-Rodríguez Luis 
Published: May 2024

ABSTRACTOccupation is considered a Social Determinant of Health (SDOH) and its effects have been studied at multiple levels. Although the inclusion of such data in the Electronic Health Record (EHR) is vital for the provision of clinical care, specially in rheumatology where work disability prevention is essential, occupation information is often either not routinely documented or captured in an unstructured manner within conventional EHR systems. Encouraged by recent advances in natural language processing and deep learning models, we propose the use of novel architectures (i.e., transformers) to detect occupation mentions in rheumatology clinical notes of a tertiary hospital, and to whom those occupations belongs. We also aimed to evaluate the clinical and demographic characteristics that influence the collection of this SDOH; and the association between occupation and patients’ diagnosis. Bivariate and multivariate logistic regression analysis were conducted for this purpose.A Spanish pre-trained language model, RoBERTa, fine-tuned with biomedical texts was used to detect occupations. The best model achieved a F1-score of 0.725 identifying occupation mentions. Moreover, highly disabling mechanical pathology diagnoses (i.e., back pain, muscle disorders) were associated with a higher probability of occupation collection. Ultimately, we determined the professions most closely associated with more than ten categories of muscu-loskeletal disorders.HighlightsDeep learning models hold significant potential for structuring and leveraging information in rheumatologyDiagnoses related to highly disabling mechanical pathology were associated with a higher probability of occupation collectionCleaners, helpers, and social workers occupations are linked to mechanical pathologies such as back pain
Reduced Likelihood of Hospitalization with the JN.1 or HV.1 SARS-CoV-2 Variants Compared to the EG.5 Variant
Authors: Levy Matthew E. , Chilunda Vanessa , Davis Richard E. , Heaton Phillip R. , Pawloski Pamala A. , Goldman Jason D. , Schandl Cynthia A. , McEwen Lisa M. , Cirulli Elizabeth T. , Wyman Dana , Rossi Andrew Dei , Dai Hang , Isaksson Magnus , Washington Nicole L. , Basler Tracy , Tsan Kevin , Nguyen Jason , Ramirez Jimmy , Sandoval Efren , Lee William , Lu James , Luo Shishi 
Published: May 2024

ABSTRACTWithin a multi-state viral genomic surveillance program, proportions of SARS-CoV-2 infections attributed to the JN.1 and HV.1 variants, compared to EG.5, were each lower among inpatients versus outpatients (aOR=0.33 [95% CI: 0.20-0.55] and aOR=0.62 [95% CI: 0.44-0.86], respectively). JN.1 and HV.1 variants may be associated with a lower risk of severe illness.
Novel Deep CNNs Explore Regions, Boundaries, and Residual Learning for COVID-19 Infection Analysis in Lung CT
Authors: Alshemaimri Bader Khalid , Khan Saddam Hussain 
Published: May 2024

AbstractCOVID-19 poses a global health crisis, necessitating precise diagnostic methods for timely containment. However, accurately delineating COVID-19 affected regions in Lung CT scans is challenging due to contrast variations and significant texture diversity. In this regard, this study introduces a novel two-stage classification and segmentation CNN approach for COVID-19 lung radiological pattern analysis. A novel Residual-BRNet is developed to integrate boundary and regional operations with residual learning, capturing key COVID-19 radiological homogeneous regions, texture variations, and structural contrast patterns in the classification stage. Subsequently, infectious CT images undergo lesion segmentation in the second stage using the newly proposed RESeg segmentation CNN. The RESeg leverages both average and max-pooling implementations to simultaneously learn region homogeneity and boundary-related patterns. Furthermore, novel pixel attention (PA) blocks are integrated into RESeg to effectively address mildly infected regions. The evaluation of the proposed Residual-BRNet CNN demonstrates promising performance metrics, achieving an accuracy of 97.97%, F1-score of 98.01%, sensitivity of 98.42%, and MCC of 96.81%. Meanwhile, PA-RESeg achieves optimal segmentation performance with an IoU score of 98.43% and a Dice Similarity score of 95.96% of the lesion region. These findings highlight the potential of the proposed diagnosis framework to assist radiologists in identifying and analyzing COVID-19 affected lung regions. The CAD GUI diagnosis tool is provided athttps://github.com/PRLAB21/COVID-19-Diagnostic-System.
Risk of common psychiatric disorders, suicidal behaviours and premature mortality following violent victimisation: A matched cohort and sibling-comparison study of 127,628 people who experienced violence in Finland and Sweden
Authors: Sariaslan Amir , Pitkänen Joonas , Forsman Jonas , Kuja-Halkola Ralf , Brikell Isabell , D’Onofrio Brian M. , Aaltonen Mikko , Larsson Henrik , Martikainen Pekka , Lichtenstein Paul , Fazel Seena 
Published: May 2024

BackgroundAssociations between violent victimisation and psychiatric disorders are hypothesised to be bidirectional, but the role of violent victimisation in the aetiologies of psychiatric disorders and other adverse outcomes remains unclear. We aimed to estimate associations between violent victimisation and subsequent common psychiatric disorders, suicidal behaviours, and premature mortality whilst accounting for unmeasured familial confounders.Methods and FindingsUsing nationwide registers, we identified a total of 127,628 individuals born in Finland (1987-2004) and Sweden (1973-2004) who had experienced violent victimisation, defined as either hospital admissions or secondary care outpatient visits for assault-related injuries. These were age- and sex-matched with up to 10 individuals in the general population (n=1,276,215) and their unaffected siblings (n=132,408). Outcomes included depression, anxiety, personality disorders, substance use disorders, suicidal behaviours, and premature mortality. Participants were followed from the victimisation date until the date of the outcome, emigration, death, or December 31, 2020, whichever occurred first. Country-specific associations were estimated using stratified Cox regression models, which also accounted for unmeasured familial confounders via sibling comparisons. The country-specific associations were then pooled using meta-analytic models.Among 127,628 patients (69.0% men) who had experienced violent victimisation, the median age at first violent victimisation was 21 (interquartile range: 18-26) years. Absolute risks of all outcomes were larger in those who were exposed to violent victimisation compared to population controls (2.3-22.5 vs. 0.6-7.3 per 1000 person-years). In adjusted models, people who had experienced violent victimisation were between two to three times as likely as their siblings to develop any of the outcomes (adjusted hazard ratios [aHRs]: 1.7-3.0). Risks remained elevated two years post-victimisation (aHRs: 1.4-2.3).ConclusionsImproving clinical assessment, management and aftercare psychosocial support could potentially reduce rates of common psychiatric disorders, suicidality and premature in individuals experiencing violent victimisation.
The Relationship Between Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Cardiovascular High-Risk: A Cross-Sectional Investigation
Authors: Li Yapeng , Shi Huiting , Liang Cui , Xie Qiaotao , Hu Haowei , Wang Haoran , Li Pengcheng 
Published: May 2024

AbstractAimsThe triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio reflects the balance between atherogenic and anti-atherogenic lipid fractions. The study aims to investigate the utility of the TG/HDL-C ratio in identifying high-risk groups for cardiovascular disease (CVD) within the general population.MethodsThe current study was a branch of the ChinaHEART cohort in middle China that involved a total of 6,593 community-dwelling adults. We examine the association between TG/HDL-C and CVD high-risk in a cross-sectional investigation.ResultsResults from restricted cubic spline and ROC analyses revealed a significant relationship between higher TG/HDL-C levels and increased odds of cardiovascular high-risk, with the ratio exhibiting good discriminatory power (AUC=0.819 in the fully adjusted model). Logistic regression further supported this association, indicating a 1.21-fold rise in the odds of high-risk for each unit increase in TG/HDL-C.ConclusionsThe TG/HDL ratio demonstrates potential as a valuable clinical tool for CVD prevention. By incorporating the TG/HDL ratio into risk assessment models, healthcare professionals can enhance risk stratification and identify high-risk individuals who may benefit from targeted interventions.
Unraveling the “indirect effects” of interventions against malaria endemicity: A systematic scoping review
Authors: Ko Yura K. , Kagaya Wataru , Chan Chim W. , Kanamori Mariko , Mbugua Samuel M. , Rotich Alex K. , Kanoi Bernard N. , Ngara Mtakai , Gitaka Jesse , Kaneko Akira 
Published: May 2024

SummaryThere is an urgent need to maximize the effectiveness of existing malaria interventions and optimize the deployment of novel countermeasures. When assessing the effects of interventions against malaria, it is imperative to consider the interdependence of people and the resulting indirect effects, without which the impact on health outcomes and their cost-effectiveness may be miscalculated. Here, we conducted a scoping review of existing literature on the indirect effects of malaria interventions. We observed a recent increase in both the number of reports and the variety of terms used to denote indirect effects. We further classified eight categories of comparative analysis to identify the indirect effects, proposed common terms for the indirect effects, and highlighted the potential benefits of mathematical models in estimating indirect effects. Improving the study design and reporting the indirect effects of malaria interventions will lead to better informed decisions by policymakers.