bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral cell polarization drives organization of epithelia in sea anemone embryos and embryonic cell aggregates
Authors: Atajanova Tavus , Kang Emily Minju , Postnikova Anna , Price Alivia Lee , Doerr Sophia , Du Michael , Ugenti Alicia , Ragkousi Katerina 
Published: April 2024

SummaryOne of the first organizing processes during animal development is the assembly of embryonic cells into epithelia. In certain animals, including Hydra and sea anemones, epithelia also emerge when cells from dissociated tissues are aggregated back together. Although cell adhesion is required to keep cells together, it is not clear whether cell polarization plays a role as epithelia emerge from disordered aggregates. Here, we demonstrate that lateral cell polarization is essential for epithelial organization in both embryos and aggregates of the sea anemoneNematostella vectensis. Specifically, knock down of the lateral polarity protein Lgl disrupts epithelia in developing embryos and impairs the capacity of dissociated cells to epithelialize from aggregates. Cells inlglmutant epithelia lose their columnar shape and have mispositioned mitotic spindles and ciliary basal bodies. Together, our data suggest that inNematostella, Lgl is required to establish lateral cell polarity and position cytoskeletal organelles in cells of embryos and aggregates duringde novoepithelial organization.
Limited Validity of Mayo Endoscopic Subscore in Ulcerative Colitis with Concomitant Primary Sclerosing Cholangitis
Authors: Wohl Pavel , Krausova Alzbeta , Wohl Petr , Fabian Ondrej , Bajer Lukas , Brezina Jan , Drastich Pavel , Hlavaty Mojmír , Novotna Petra , Kahle Michal , Spicak Julius , Gregor Martin 
Published: April 2024

AbstractBackground and AimsUlcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. Here, we sought to compare MES in a cohort of UC and PSC-UC patients and assess the accuracy using histological activity scoring (Nancy histological index; NHI).MethodsMES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the caecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected.ResultsThe median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum), but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the caecum). There was a correlation between MES and NHI for UC patients (Spearman’s ρ = 0.40, p = 0.029), but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in another 11% of PSC-UC patients.ConclusionMES fails to identify microscopic signs of inflammation in the context of PSC-UC. This indicates that histological evaluation should become an integral part of the diagnostic and grading system in both PSC-UC and PSC.
Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition
Authors: Perry Andrew S. , Piaggi Paolo , Huang Shi , Nayor Matthew , Freedman Jane , North Kari , Below Jennifer , Clish Clary , Murthy Venkatesh L. , Krakoff Jonathan , Shah Ravi V. 
Published: April 2024

AbstractThe emerging field of precision nutrition is based on the notion that inter-individual responses across diets of different calorie-macronutrient content may contribute to inter-individual differences in metabolism, adiposity, and weight gain. Free-living diet studies have been traditionally challenged by difficulties in controlling adherence to prescribed calories and macronutrient content and rarely allow a period of metabolic stability prior to metabolic measures (to minimize influences of weight changes). In this context, key physiologic measures central to precision nutrition responses may be most precisely quantified via whole room indirect calorimetry over 24-h, in which precise control of activity and nutrition can be achieved. In addition, these studies represent unique “N of 1” human crossover metabolic-physiologic experiments during which specific molecular pathways central to nutrient metabolism may be discerned. Here, we quantified 263 circulating metabolites during a ≈40-day inpatient admission in which up to 94 participants underwent seven monitored 24-h nutritional interventions of differing macronutrient composition in a whole-room indirect calorimeter to capture precision metabolic responses. Broadly, we observed heterogenous responses in metabolites across dietary chambers, with the exception of carnitines which tracked with 24-h respiratory quotient. We identified excursions in shared metabolic species (e.g., carnitines, glycerophospholipids, amino acids) that mapped onto gold-standard calorimetric measures of substrate oxidation preference and lipid availability. These findings support a coordinated metabolic-physiologic response to nutrition, highlighting the relevance of these controlled settings to uncover biological pathways of energy utilization during precision nutrition studies.
DCAE-SR: Design of a Denoising Convolutional Autoencoder for reconstructing Electrocardiograms signals at Super Resolution
Authors: Lomoio Ugo , Veltri Pierangelo , Guzzi Pietro Hiram , Liò Pietro 
Published: April 2024

AbstractElectrocardiogram (ECG) signals play a pivotal role in cardiovascular diagnostics, providing essential information on the electrical activity of the heart. However, the inherent noise and limited resolution in ECG recordings can hinder accurate interpretation and diagnosis. In this paper, we propose a novel model for ECG super resolution (SR) that uses a DNAE to enhance temporal and frequency information inside ECG signals. Our approach addresses the limitations of traditional ECG signal processing techniques. Our model takes in input 5-second length ECG windows sampled at 50 Hz (very low resolution) and it is able to reconstruct a denoised super-resolution signal with an x10 upsampling rate (sampled at 500 Hz). We trained the proposed DCAE-SR on public available myocardial infraction ECG signals. Our method demonstrates superior performance in reconstructing high-resolution ECG signals from very low-resolution signals with a sampling rate of 50 Hz. We compared our results with the current deep-learning literature approaches for ECG super-resolution and some non-deep learning reproducible methods that can perform both super-resolution and de-noising. We obtained current state-of-the-art performances in super-resolution of very low resolution ECG signals frequently corrupted by ECG artifacts. We were able to obtain a signal-to-noise ratio of 12.20 dB (outperforms previous 4.68 dB), mean squared error of 0.0044 (outperforms previous 0.0154) and root mean squared error of 4.86% (outperforms previous 12.40%). In conclusion, our DCAE-SR model offers a robust (to artefact presence), versatile and explainable solution to enhance the quality of ECG signals. This advancement holds promise in advancing the field of cardiovascular diagnostics, paving the way for improved patient care and high-quality clinical decisions.
Continued underutilization with pronounced geographic variation in clozapine use
Authors: Cavanah Luke R. , Tian Maria Y. , Goldhirsh Jessica L. , Huey Leighton Y. , Piper Brian J. 
Published: April 2024

AbstractIntroductionSchizophrenia-spectrum disorders are debilitating and contribute to a substantial economic burden. Clinicians have historically underutilized clozapine, an atypical antipsychotic traditionally reserved for use in treatment-resistant schizophrenia, due to the medication’s adverse effect profile and associated management requirements, concerns of poor treatment adherence, and poor training/exposure to the use. In addition to alleviating schizophrenia symptoms when multiple other medications have failed, clozapine has other unique benefits that compel its use such as its use being associated with reduced suicide ideation and action, aggression, substance use, and all-cause mortality.MethodsThis study aimed to characterize clozapine utilization by US Medicare patients from 2015-20. Additionally, we identified the states that prescribed significantly different amounts than the national average.ResultsWe observed a steady decrease in clozapine use adjusted for population (−18.0%) and spending (−24.9%) over time. For all years, there was significant geographic heterogeneity (average: nine-fold) in population-corrected clozapine use. Massachusetts (2015-20: 95.4, 82.7, 76.8, 72.2, 71.2, 63.7 prescriptions per thousand enrollees) and South Dakota (2015-20: 78.0, 77.4, 78.4, 75.6, 72.0, 71.6) were the only states that prescribed significantly more than average, and none prescribed significantly less.DiscussionClozapine use by US Medicare patients is low, decreasing, and concerning for underutilization—patterns likewise seen for the US Medicaid recipients. Further study of the reasons for the state variation is needed. Education interventions, training reform, and devices that ease required routine blood monitoring are all practical solutions to optimize clozapine use.
Post-stroke Epilepsy and its Association with Stroke Location – Systematic review and Meta-analysis
Authors: Park Sihyeong , Esengul Yasar T. , Gharaibeh Khaled , Saleem Sidra , Sheikh Ajaz 
Published: April 2024

AbstractObjectiveThere have been several meta-analytic studies that investigated potential risk factors for post-stroke epilepsy (PSE)1,2. Cortical location is known to be associated with increased risk of PSE. However, relationship between the involvement of specific lobe with stroke and PSE has not been evaluated in a meta-analysis due to unavailability of relevant data. To the best of our knowledge, this is the first meta-analysis on this subject matter.MethodsThe PubMed and Embase databases were comprehensively assessed and searched for studies that evaluated the association between the involvement of different lobes with PSE. Studies that evaluated post-stroke epilepsy or recurrent post-stroke seizure were included, and acute symptomatic seizure was excluded. Following search strategy was used, “post-stroke” OR “stroke” OR “intracerebral hemorrhage” AND “epilepsy” OR “seizure” AND “lobe” OR “territory” OR “location”. Joanna Briggs Institute appraisal tool was utilized to perform quality assessment of the included studies. A random effects model was used to estimate pooled odds ratio of the selected outcomes with 95 percent confidence intervals (CIs), and the study heterogeneity was analyzed.ResultsNine studies3-11were identified with 1328 stroke patients. 9/9 studies showed association of frontal lobe involvement with higher likelihood of PSE (OR=2.10, 95% CI=1.37-3.21, p-value=0.0007). All studies showed association of parietal stroke with increased likelihood of PSE (OR=2.85, 95% CI=1.93-4.22, p-value<0.00001). Previous temporal lobe stroke was associated with increased risk of PSE (OR=3.55, 95% CI=1.95-6.45, p-value<0.00001). In contrast, association between occipital lobe involvement and PSE was not statistically significant (OR=1.37, 95% CI=0.95-1.96, p-value<0.09), and this remained true when subgroup analysis was performed.DiscussionOur meta-analysis shows that PSE is associated with frontal, parietal, and temporal involvement of previous stroke. There was no statistically significant association between occipital lobe involvement and PSE. Further high quality studies are needed to investigate if stroke in one lobe/territory can be more epileptogenic than those in others.Key PointsCerebrovascular disease is the most common etiology of newly diagnosed epilepsyPrior stroke involving the frontal, temporal, or parietal lobe is associated with increased risk of post-stroke epilepsyOccipital lobe stroke is not associated with increased risk of post-stroke epilepsy, regardless of the age group.
Detection of measles virus genotype D8 in wastewater of Brussels capital region, Belgium, March 2024
Authors: Rector Annabel , Bloemen Mandy , Hoorelbeke Bart , Van Ranst Marc , Wollants Elke 
Published: April 2024

AbstractFollowing the European Centre for Disease Prevention and Control (ECDC) threat assessment brief regarding increased measles case numbers and outbreaks in Europe, we investigated sewage samples from different wastewater treatment plants in Belgium for the presence of measles virus (MV). Samples taken from Brussels North were found to contain MV, which could be characterized as genotype D8. Twelve measles cases were reported in the Brussels capital region in February/March 2024, but additional infections are likely occurring under the radar.
Tracheal aspirate metagenomics reveals association of antibiotic resistance with non-pulmonary sepsis mortality
Authors: Rodríguez-Pérez Héctor , Ciuffreda Laura , Hernández-Beeftink Tamara , Guillen-Guio Beatriz , Domínguez David , Corrales Almudena , Espinosa Elena , Alcoba-Florez Julia , Lorenzo-Salazar Jose M. , González-Montelongo Rafaela , Villar Jesús , Flores Carlos 
Published: April 2024

AbstractBackgroundPrevious metabarcoding studies based on 16S rRNA sequencing in patients with extrapulmonary sepsis have found early pulmonary dysbiosis associated with a poor prognosis. To further discern this association, here we aimed to better characterize the pulmonary bacterial communities in these patients by leveraging metagenomics and to evaluate if the presence of antibiotic resistance genes (ARGs) could explain the higher mortality of the patients.Material and methodsMetagenomic sequencing was performed using the Nextera XT Library Prep Kit and HiSeq 4000 (Illumina Inc.) on tracheal aspirate samples that were obtained within 24 h from diagnosis from patients with extrapulmonary sepsis admitted to the Intensive Care Unit (ICU). Analysis involved MetaSpades for contig assembly, Kraken2 and Metaphlan4 for taxonomic classification, and CARD and GTDB-tk for ARGs annotation and assignment to the bacterial species. The relationship between the presence of antibiotic resistance and ICU mortality was evaluated using the Wilcoxon test and logistic regression models adjusting for clinical and demographic variables.ResultsIn total, 127 different ARGs were detected circumscribed only to seven patients. The most common ARGs found were from the antibiotic groups of aminoglycosides and beta-lactams, both present in most of the patients. These ARGs were found, almost entirely linked toKlebsiella pneumoniae, Escherichia coli, andPseudomonas aeruginosa. The results also show a significant enrichment of ARGs among patients who died while admitted in the ICU (57%, 95% confidence interval [CI]: 18-90%) compared to surviving patients (20%, 95% CI: 7-40%) (p=0.022). Analyses adjusting for clinical and demographic variables did not alter this result.ConclusionMetagenomic sequencing has allowed an unprecedented characterization of the sepsis lung microbiome showing that antibiotic resistance is common among these patients. The results also suggest a relationship between the early accumulation of ARGs in the lung of patients with extrapulmonary sepsis who die while admitted in the ICU. Studies in independent samples will be needed to validate our findings.
Altered functional connectivity between cortical premotor areas and the spinal cord in chronic stroke
Authors: Braaß Hanna , Wolf Silke , Feldheim Jan , Chu Ying , Tinnermann Alexandra , Finsterbusch Jürgen , Büchel Christian , Gerloff Christian , Schulz Robert 
Published: April 2024

AbstractBackgroundNeuroscience research has contributed significantly to understanding alterations in brain structure and function after ischemic stroke. Technical limitations have excluded the spinal cord from imaging-based research. Available data are restricted to a few microstructural analyses, and functional connectivity data are absent. The present study attempted to close this knowledge gap and assess alterations in corticospinal activation and coupling changes in chronic stroke.MethodsThirteen well-recovered stroke patients underwent corticospinal functional MRI while performing a simple force generation task. Task-related activation was localized in the ipsilesional primary motor cortex (M1), ventral premotor cortex (PMV), and supplementary motor area (SMA), as well as in the cervical spinal cord. Psycho-physiological interactions and linear modeling were used to infer functional connectivity between cortical motor regions and the cervical spinal cord and their associations with motor deficits.ResultsThe main finding was that PMV and SMA showed topographically distinct alterations in their connectivity with the spinal cord. Specifically, we found a reduced coupling between SMA and the ipsilateral ventral spinal cord and an enhanced coupling between PMV and ventral and intermediate central spinal zones. Lower SMA- and higher PMV-related spinal cord couplings were correlated with residual deficits.ConclusionThis work provides first-in-human functional insights into stroke-related alterations in the functional connectivity between cortical motor areas and the spinal cord, suggesting that different premotor areas and spinal neuronal assemblies might be involved in coupling changes. It adds a novel, promising approach to better understanding stroke recovery and developing innovative models to comprehend treatment strategies with spinal cord stimulation.
Vaccination and collective action under social norms
Authors: Morsky Bryce 
Published: April 2024

AbstractSocial dynamics are an integral part of the spread of disease affecting contact rates as well as the adoption of pharmaceutical and non-pharmaceutical interventions. When vaccines provide waning immunity, efficient and timely uptake of boosters is required to maintain protection and flatten the curve of infections. How then do social dynamics affect the timely up-take of vaccines and thereby the course of an epidemic? To explore this scenario, a behavioural-epidemiological is developed here. It features a tipping-point dynamic for the uptake of vaccines that combines the risk of infection, perceived morbidity risk of the vaccine, and social payoffs for deviating from the vaccination decision making of others. The social payoffs are derived from a social norm of conformity, and they create a collective action problem. A key finding driven by this dilemma is that waves of vaccine uptake and infections can occur due to inefficient and delayed uptake of boosters. This results in a nonlinear response of the infection load to the transmission rate: an intermediate transmission rate can result in greater prevalence of disease relative to more or less transmissible diseases. Further, global information about the prevalence of the disease and vaccine uptake increases the infection load and peak relative to information restricted to individuals’ contact net-works. Thus, decisions driven by local information can mitigate the collective action problem across the population. Finally, the optimal public policy program to promote boosters is shown to be one that focuses on overcoming the social inertia to vaccinate at the start of an epidemic.
Optimized patient-specific immune checkpoint inhibitors therapy for cancer treatment based on tumor immune microenvironment modeling
Authors: Yao Yao , Chen Frank Youhua , Zhang Qingpeng 
Published: April 2024

ABSTRACTObjectiveEnhancing patient response to immune checkpoint inhibitors (ICIs) is crucial in cancer immunotherapy. We aim to create a data-driven mathematical model of the tumor immune microenvironment (TIME) and utilize deep reinforcement learning (DRL) to optimize patient-specific ICI therapy combined with chemotherapy (ICC).MethodsUsing patients’ genomic and transcriptomic data, we develop an ordinary differential equations (ODEs)-based TIME model to characterize interactions among chemotherapy, ICIs, immune cells, and cancer cells. A DRL algorithm is trained to determine the personalized optimal ICC therapy.ResultsNumerical experiments with real-world data demonstrates that the proposed TIME model can predict ICI therapy response. The DRL-derived personalized ICC therapy outperforms predefined fixed schedules. For tumors with extremely low CD8+T cell infiltration (“extremely cold tumors”), DRL recommends high-dosage chemotherapy alone. For tumors with higher CD8+T cell infiltration (“cold” and “hot tumors”), an appropriate chemotherapy dosage induces CD8+T cell proliferation, enhancing ICI therapy outcomes. Specifically, for “hot tumors,” chemotherapy and ICI are administered simultaneously, while for “cold tumors,” a mid-dosage of chemotherapy makes the TIME “hotter” before ICI administration. However, a number of “cold tumors” with rapid resistant cancer cell growth, ICC eventually fails.ConclusionThis study highlights the potential of utilizing real-world clinical data and DRL to develop personalized optimal ICC by understanding the complex biological dynamics of a patient’s TIME. Our ODE-based TIME model offers a theoretical framework for determining the best use of ICI, and the proposed DRL model may guide personalized ICC schedules.SIGNIFICANCE STATEMENTOur research presents a novel data-driven approach to personalized cancer treatment by combining artificial intelligence and mathematical models of the tumor’s surrounding environment, known as the tumor immune microenvironment (TIME). This innovative method allows for the optimization of patient-specific immune checkpoint inhibitors and combined chemotherapy therapy. By utilizing deep reinforcement learning, our approach can adapt and improve treatment strategies for individual patients, ultimately maximizing the effectiveness of cancer therapies. This pioneering work has the potential to significantly enhance clinical decision-making and improve patient outcomes, paving the way for personalized cancer immunotherapy.
The potential of gene drive releases in malaria vector species to reduce the malaria burden in different African environments
Authors: Hancock Penelope A. , North Ace , Leach Adrian W. , Winskill Peter , Ghani Azra , Godfray H. Charles J. , Burt Austin , Mumford John D. 
Published: April 2024

ABSTRACTGene drive technologies are a promising means of malaria control with the potential to cause widespread and sustained reductions in transmission. In real environments, however, gene drive impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of a gene drive that causes vector population suppression. We apply the model to sixteen ∼12,000km2areas of west Africa that span variation in vector ecology and malaria prevalence. We simulate gene drive releases targeting different vector species combinations, and estimate reductions in vector abundance, malaria prevalence and clinical cases in children. Average reductions in vector abundance ranged from 77.3%-99.1% across areas when the gene drive releases targeted all major vector species (Anopheles gambiae,An. coluzzii,An. arabiensis,andAn. funestus). Impacts on malaria depended strongly on which vector species were targeted. Consistently strong impacts required releases targeting all vector species, which reduced prevalence by over 90% in all areas. When the major vector speciesAn. gambiaeandAn. coluzziiwere targeted, average reductions in prevalence ranged from no reduction to 72% across areas, and reductions in cumulative clinical cases ranged from zero to 57%. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results give new insights into the factors determining the impacts of gene drives on malaria across different African settings.