bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-Effectiveness of Prefusion F Protein-Based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States
Authors: Moghadas Seyed M. , Shoukat Affan , Bawden Carolyn E. , Langley Joanne M. , Singer Burton H , Fitzpatrick Meagan C. , Galvani Alison P. 
Published: August 2023

AbstractBackgroundTwo prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against Respiratory Syncytial Virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines.MethodsWe developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the US. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-years (QALY) gained as a measure of effectiveness, and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective.ResultsUsing a willingness-to-pay of $95,000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD under $120 with Arexvy and $111 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the US, the budget impact of these programs at the maximum PPD ranged from $5.74 to $6.10 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $250 for Arexvy and $233 for Abrysvo, with two-year budget impacts of $11.59 and $10.89 billion, respectively.ConclusionsVaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.
Protective effects of sacubitril/valsartan in anthracyclines-induced cardiotoxicity: A Systematic Review and Meta-Analysis
Authors: López Trejo Felipe Israel , Sánchez Barrera Mónica Daniela , Andrade Cuellar Elias Noel , Morales Portano Julieta Danira , Martínez Martínez Laura Aline 
Published: August 2023

ABSTRACTBackgroundOne of the adverse effects of anthracycline use is cardiotoxicity manifested as heart failure. The benefit of sacubitril/valsartan in patients with heart failure of ischemic origin has been demonstrated, but not due to toxicity. Our objective was to determine if there are protective effects of the use of sacubitril/valsartan in cardiotoxicity induced by anthracyclines.MethodsA bibliographic search was carried out in PubMed, Cochrane Library, LILACS, Scopus, EBSCO and Google Scholar. A systematic review and meta-analysis was performed to assess mean differences (MD) with 95% confidence intervals following the PRISMA Statement.Results558 published articles were found, of which three were submitted to analysis, with a total sample of 69 patients. With the use of sacubitril/valsartan there was an increase in the percentage of left ventricular ejection fraction (LVEF) [MD 6.78% (p < 0.001)], an increase in the percentage of global longitudinal strain of the left ventricle (LV-GLS) [MD 3.37 % (p < 0.001)], and decreased serum levels of NT-proBNP [MD −1003.64 pg/mL (p < 0.001)]; in addition, there was an increase in the distance traveled with the use of sacubitril/valsartan [MD 95.23 meters (p < 0.001)] compared to their baseline values, respectively.ConclusionsThis meta-analysis suggests that there is a benefit from the use of sacubitril/valsartan in patients with heart failure related to the use of anthracyclines on ventricular remodeling and functional capacity. This is the first meta-analysis to our knowledge evaluating this effect. Randomized double-blind placebo-controlled clinical trials are required to confirm these findings.
Intracerebral Hemorrhage etiological classification systems and their correlation with neurological deterioration
Authors: Vázquez-Justes Daniel , Mauri-Capdevila Gerard , Yhovany Gallego , Paul-Arias Miriam , Mitjana Raquel , Purroy Francisco 
Published: August 2023

AbstractIntroductionUnlike ischemic stroke, the etiological classification of patients with intracerebral hemorrhage (CH) lacks consensus. Our study focuses on two commonly-used classification systems: SMASH-U and H-ATOMIC. The main difference between them lies in the fact that the H-ATOMIC system considers the simultaneous presence of different etiologies in a single patient. The association between the two classifications with relation to neurological deterioration (ND) and clinical outcomes remains so far unexplored.MethodsWe recruited consecutive ICH patients from 2015 to 2022, determining etiology was on discharge. Demographic, radiological and clinical characteristics were recorded. ND during hospitalization in the 7 days after stroke was the main clinical endpoint.Results301 patients were recruited. 124 patients (41.2%) experienced ND. The hypertensive subtype was the most frequent etiology with both classifications. In 149 (49.5%) more than one possible etiology for the ICH were recognized. The most frequent combination was hypertension + either probable or possible amyloid angiopathy, in 64 patients (21.3%). Significant differences in ND proportions were observed across groups with both systems. ICH related to anticoagulation was associated with a greater risk of ND: 63.5 % in SMASH-U and 62.5% in patients with a combination of Hypertension and Oral Anticoagulants in H-ATOMIC. Both these etiological groups and that containing combined etiologies were statistically significant according to multivariate analysis. Intraventricular extension, blood pressure control and initial volume were also related to ND.ConclusionEtiology of the ICH could be related to the risk of ND during hospitalization. Anticoagulation-related etiologies may present the highest risk, especially when combined with hypertension.
TgF344-AD rat model of Alzheimer’s disease: spatial disorientation and asymmetry in hemispheric neurodegeneration
Authors: Sagalajev Boriss , Lennartz Lina , Vieth Lukas , Gunawan Cecilia Tasya , Neumaier Bernd , Drzezga Alexander , Visser-Vandewalle Veerle , Endepols Heike , Sesia Thibaut 
Published: August 2023

AbstractBACKGROUNDThe TgF344-AD ratline represents a transgenic animal model of Alzheimer’s disease (AD). We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aimed to investigate whether TgF344-AD rats exhibit signs of asymmetry in hemispheric neurodegeneration, similar to what is reported in spatially disoriented AD patients. Finally, we sought to examine how spatial disorientation correlates with working memory performance.METHODSTgF344-AD rats were divided into two groups balanced by sex and genotype. The first group underwent the delayed match-to-sample (DMS) task for the assessment of spatial orientation and working memory, while the second group underwent positron emission tomography (PET) for the assessment of glucose metabolism and microglial activity as in-vivo markers of neurodegeneration. Rats were 13 months old during DMS training and 14-16 months old during DMS testing and PET.RESULTSIn the DMS task, TgF344-AD rats were more likely than their wild-type littermates to display strong preference for one of the two levers, preventing working memory testing. Rats without lever-preference showed similar working memory, regardless of their genotype. PET revealed hemispherically asymmetric clusters of increased microglial activity and altered glucose metabolism in TgF344-AD rats.CONCLUSIONSTgF344-AD rats display spatial disorientation and hemispherically asymmetrical neurodegeneration, suggesting a potential causal relationship consistent with clinical observations. In rats without spatial disorientation, working memory remains intact.
Action planning modulates perceptual confidence through action monitoring processes
Authors: Sanchez Rémi , Davranche Karen , Gajdos Thibaut , Desantis Andrea 
Published: August 2023

AbstractDominant models of metacognition suggest that sensory information quality determines perceptual confidence, but recent accounts propose that motor signals also affect confidence judgments. In this study, we investigated the impact of motor planning of perceptual responses on decision confidence, testing two hypotheses. The “fluency hypothesis” suggests that ease of motor response selection and preparation enhances confidence. In contrast, the “monitoring hypothesis” posits that increased action monitoring during response selection boosts confidence, potentially counteracting response fluency. In three pre-registered experiments, participants reported the orientation of a stimulus and indicated their confidence in their response. A cue induced action planning that was either congruent or incongruent with the response side used to report the stimulus orientation. Across experiments, we consistently observed higher confidence when participants prepared spatially incongruent actions compared to congruent ones, regardless of response accuracy. In the third experiment, electroencephalography (EEG) revealed an increased fronto-central P2 amplitude for incongruent actions, suggesting that incongruent action planning heightened early attentional resources needed to resolve response conflict. Incongruent action plans also modulated post-response ERPs at centro-parietal channels (e.g., Pz), typically linked to confidence and error monitoring. These findings align with the “monitoring hypothesis” suggesting that the degree of action monitoring during response selection modulates retrospective decision confidence.Public Significance StatementWhile virtually every decision we make leads to an action, the role of motor processes in decision making has been largely neglected. Our results show that retrospective confidence in a perceptual discrimination task is boosted when the motor execution is spatially incongruent with motor preparation, independently of the correctness of the response. Electroencephalography recordings indicate that this effect could be explained by a larger involvement of early attentional resources related to action monitoring, which has an impact on confidence computations. Taken together, these results suggest that action planning information might trigger monitoring mechanisms susceptible to alter retrospective confidence in our decisions, implying that motor processes are not only the output, but also an input of the decision mechanisms.
Agent-based model demonstrates the impact of nonlinear, complex interactions between cytokines on muscle regeneration
Authors: Haase Megan , Comlekoglu Tien , Petrucciani Alexa , Peirce Shayn M. , Blemker Silvia S. 
Published: August 2023

AbstractMuscle regeneration is a complex process due to dynamic and multiscale biochemical and cellular interactions, making it difficult to identify microenvironmental conditions that are beneficial to muscle recovery from injury using experimental approaches alone. To understand the degree to which individual cellular behaviors impact endogenous mechanisms of muscle recovery, we developed an agent-based model (ABM) using the Cellular Potts framework to simulate the dynamic microenvironment of a cross-section of murine skeletal muscle tissue. We referenced more than 100 published studies to define over 100 parameters and rules that dictate the behavior of muscle fibers, satellite stem cells (SSC), fibroblasts, neutrophils, macrophages, microvessels, and lymphatic vessels, as well as their interactions with each other and the microenvironment. We utilized parameter density estimation to calibrate the model to temporal biological datasets describing cross-sectional area (CSA) recovery, SSC, and fibroblast cell counts at multiple time points following injury. The calibrated model was validated by comparison of other model outputs (macrophage, neutrophil, and capillaries counts) to experimental observations. Predictions for eight model perturbations that varied cell or cytokine input conditions were compared to published experimental studies to validate model predictive capabilities. We used Latin hypercube sampling and partial rank correlation coefficient to identifyin silicoperturbations of cytokine diffusion coefficients and decay rates to enhance CSA recovery. This analysis suggests that combined alterations of specific cytokine decay and diffusion parameters result in greater fibroblast and SSC proliferation compared to individual perturbations with a 13% increase in CSA recovery compared to unaltered regeneration at 28 days. These results enable guided development of therapeutic strategies that similarly alter muscle physiology (i.e. converting ECM-bound cytokines into freely diffusible forms as studied in cancer therapeutics or delivery of exogenous cytokines) during regeneration to enhance muscle recovery after injury.
Neural geometrodynamics, complexity, and plasticity: a psychedelics perspective
Authors: Ruffini G. , Lopez-Sola E. , Vohryzek J. , Sanchez-Todo R. 
Published: August 2023

AbstractWe explore the intersection of neural dynamics and the effects of psychedelics in light of distinct timescales in a framework integrating concepts from dynamics, complexity, and plasticity. We call this frameworkneural geometrodynamicsfor its parallels with general relativity’s description of the interplay of spacetime and matter. The geometry of trajectories within the dynamical landscape of “fast time” dynamics are shaped by the structure of a differential equation and its connectivity parameters, which themselves evolve over “slow time” driven by state-dependent and state-independent plasticity mechanisms. Finally, the adjustment of plasticity processes (metaplasticity) takes place in an “ultraslow” time scale. Psychedelics flatten the neural landscape, leading to heightened entropy and complexity of neural dynamics, as observed in neuroimaging and modeling studies linking increases in complexity with a disruption of functional integration. We highlight the relationship between criticality, the complexity of fast neural dynamics, and synaptic plasticity. Pathological, rigid, or “canalized” neural dynamics result in an ultrastable confined repertoire, allowing slower plastic changes to consolidate them further. However, under the influence of psychedelics, the destabilizing emergence of complex dynamics leads to a more fluid and adaptable neural state in a process that is amplified by the plasticity-enhancing effects of psychedelics. This shift manifests as an acute systemic increase of disorder and a possibly longer-lasting increase in complexity affecting both short-term dynamics and long-term plastic processes. Our framework offers a holistic perspective of the acute effects of these substances and their potential long-term impacts on neural structure and function.
Population coding of time-varying sounds in the non-lemniscal Inferior Colliculus
Authors: Shi Kaiwen , Quass Gunnar L. , Rogalla Meike M. , Ford Alexander N. , Czarny Jordyn E. , Apostolides Pierre F. 
Published: August 2023

AbstractThe inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. The IC’s non-lemniscal, dorsal “shell” region is likely important for this process, as neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals to the amygdala and non-primary auditory cortices; forebrain circuits important for vocalization coding in a variety of mammals, including humans. However, the extent to which shell IC neurons transmit acoustic features necessary to discern vocalizations is less clear, owing to the technical difficulty of recording from neurons in the IC’s superficial layers via traditional approaches. Here we use 2-photon Ca2+imaging in mice of either sex to test how shell IC neuron populations encode the rate and depth of amplitude modulation, important sound cues for speech perception. Most shell IC neurons were broadly tuned, with a low neurometric discrimination of amplitude modulation rate; only a subset were highly selective to specific modulation rates. Nevertheless, neural network classifier trained on fluorescence data from shell IC neuron populations accurately classified amplitude modulation rate, and decoding accuracy was only marginally reduced when highly tuned neurons were omitted from training data. Rather, classifier accuracy increased monotonically with the modulation depth of the training data, such that classifiers trained on full-depth modulated sounds had median decoding errors of ∼0.2 octaves. Thus, shell IC neurons may transmit time-varying signals via a population code, with perhaps limited reliance on the discriminative capacity of any individual neuron.Significance StatementThe IC’s shell layers originate a “non-lemniscal” pathway whose first- and second-order targets are thought important for perceiving conspecific vocalizations and human speech. However, prior studies suggest that individual shell IC neurons are broadly tuned and have high response thresholds, implying a limited reliability of efferent signals. Here we use Ca2+imaging to test how shell IC neurons encode amplitude modulation, a key sound cue for speech perception and stream segregation. We show that the rate and depth of amplitude modulation is accurately represented in the ensemble activity of shell IC neuron populations. Thus, downstream targets can read out a sound’s temporal envelope from a distributed rate code transmitted by populations of broadly tuned neurons.
Air-Liquid Interface Induced Epithelial Delamination
Authors: Liu Chunzi , Fuller Gerald G. 
Published: August 2023

AbstractMany epithelial tissues reside at air-liquid interfaces, as exemplified by the ocular epithelium, oral mucosa, and alveolar epithelium. The interfacial tension across the epithelial tissues imposes a mechanical challenge to the homeostasis of the tissue. However, the interplay between interfacial properties and homeostasis in biological samples has been overlooked due to a lack of suitable measurement methods and theoretical developments. Here we described a surprising observation in which the surface energy at cell-air interface is sufficient to delaminate a stratified ocular epithelium from its substrate. We demonstrated that the interfacial tension at the epithelium-fluid interfaces can be measured using a modified Schultz method. The measured value is conceptually and numerically distinctive to the tensile modulus measured by deformation-based methods, such as micropippeting and tissue surface tensiometers. Furthermore, a mechanical analysis at the cell-air-liquid triple line during the delamination process revealed a strain hardening behavior of the epithelial layers. Finally, perturbations on different junctional protein complexes revealed that a delicate balance among cortical tension, focal adhesion, and cell-liquid interfacial tension is required for the epithelial tissue mechanical stability.
Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk
Authors: Bode Hannes Frederik , He Liang , Hjelmborg Jacob V.B. , Kaprio Jaakko , Ollikainen Miina 
Published: August 2023

AbstractBackgroundAssessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health related behavior or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood, however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior.ResultsPre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 and censoring 75.2 years. We identified 212 CpGs (p<6.4*10−8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risk associated CpGs were hypomethylated and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian Randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body ofNXN, rs480351) with increased risk for estrogen-receptor positive BC and decreased risk for estrogen-receptor negative BC.ConclusionWhile causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures.
Predicting appropriateness of antibiotic treatment among ICU patients with hospital acquired infection
Authors: Rannon Ella , Goldschmidt Ella , Bernstein Daniel , Wasserman Asaf , Coster Dan , Shamir Ron 
Published: August 2023

AbstractAntimicrobial resistance is a growing threat to global health, leading to ineffective treatment of infection and increasing treatment failure, mortality, and healthcare costs. Inappropriate antibiotic therapy is often administered in the Intensive Care Unit (ICU) due to the urgency of treatment, but can lead to poor patient outcomes. In this study, we developed a machine learning model that predicts the appropriateness of antibiotic treatments for ICU inpatients with ICU-acquired blood infection. We analyzed data from electronic medical records (EMRs), including demographics, administered drugs, previous microbiological cultures, invasive procedures, lab measurements and vital signs. Since EMRs have high rates of missing values and since our cohort is relatively small and imbalanced, we introduced novel computational methods to address these issues. The final model achieved an AUROC of 82.8% and an AUPR of 60.6% on the training set and an AUROC score of 77.3% and an AUPR score of 40.4% on the validation set. Our study shows the potential of machine learning models for inappropriate antibiotic treatment prediction.