bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derivation and validation of a prediction rule for sedative-associated delirium during acute respiratory failure requiring mechanical ventilation
Authors: Prendergast Niall T. , Onyemekwu Chukwudi A. , Potter Kelly M. , Franz Christopher A. , Kitsios Georgios D. , McVerry Bryan J. , Pandharipande Pratik P. , Ely E. Wesley , Girard Timothy D. 
Published: October 2024

AbstractBackgroundDelirium during acute respiratory failure is common and morbid. Pharmacologic sedation is a major risk factor for delirium, but some sedation is often necessary for the provision of safe care of mechanically ventilated patients. A simple, transparent model that predicts sedative-associated delirium in mechanically ventilated ICU patients could be used to guide decisions about personalized sedation.Research QuestionCan the risk of sedative-associated delirium be estimated in mechanically-ventilated ICU patients?Study Design and MethodsUsing the subset of patients in a previously-published ICU cohort who received mechanical ventilation, we performed backward stepwise logistic regression to derive a model predictive of sedative-associated delirium. We validated this model internally using hundredfold bootstrapping. We then validated this model externally in a separate prospective cohort of mechanically ventilated ICU patients.Results836 patients comprised the derivation cohort. Backwards stepwise regression produced a model with age, BMI, sepsis, SOFA, malignancy, COPD, stroke, sex, and doses of sedatives (opioids, propofol, and/or benzodiazepines) as predictors of sedative-associated delirium. The model had very good discriminative power, with an area under the receiver-operator curve (AUROC) of 0.83. Internal validation via bootstrapping showed preserved discriminatory function with an AUROC of 0.81 and graphical evidence of good calibration. External validation in a separate set of 340 patients showed good discrimination, with AUROC of 0.70.InterpretationSedative-associated delirium during acute respiratory failure requiring mechanical ventilation can be predicted using a simple, transparent model, which can now be validated in a prospective study.
Prism Adaptation-Induced Modulation of Cortical Excitability of Upper and Lower Limb Muscles is Enhanced with Electrical Stimulation
Authors: Aloba Fisayo K , Hope Jasmine M , Spencer Jacob , Muthukumar Maithri , Leone Taylor M , Parikh Vyoma , Chen Peii , Borich Michael R , Kesar Trisha M 
Published: October 2024

AbstractBackgroundPrism adaptation (PA) is a sensorimotor behavioral phenomenon. Right shifting PA induces a shift in global visuospatial motor behavior toward the left hemi-space (aftereffect) leading to immediate and transient changes in visuomotor behavior. Non-invasive sensorimotor electrical stimulation (Stim) may upregulate corticomotor excitability, is commonly used as a therapeutic adjunct during motor training, and may accentuate the effects of PA. However, the cortical plasticity mechanisms related to the behavioral effects of PA, its generalization to the lower limb, and the combinatorial effects of PA and Stim are poorly understood.ObjectiveTo evaluate the effects of combining PA with Stim on corticomotor excitability and visuo-spatial-motor behavior, and its generalization to the lower limb.MethodsWe used a repeated-measures design to evaluate the effects of 1 session of PA with and without Stim in 15 young able-bodied individuals (18-35 years). Before and after PA, visuomotor pointing task performance, corticomotor excitability, short-interval intra-cortical inhibition (SICI), long-interval intra-cortical inhibition (LICI), and intra-cortical facilitation (ICF) were evaluated in bilateral upper and left ankle muscles with motor-evoked potentials (MEPs) elicited from single and paired-pulse transcranial magnetic stimulation (TMS).ResultsBehaviorally, both PA+Stim and PA+Sham showed significant sensorimotor aftereffects, inducing a leftward shift in visuo-spatial and proprioceptive pointing. Neurophysiologically, suprathreshold MEP amplitude increased in the left first dorsal interossei (FDI) and left soleus following the PA+Stim condition but not the PA+Sham condition. PA+Stim showed statistical trends for inducing larger changes in ICF of the left FDI and left tibialis anterior. Additionally, compared to PA+Stim, PA+Sham induced larger changes in LICI of the left FDI and left tibialis anterior, and in SICI of the left tibialis anterior.ConclusionAlthough both PA+Stim and PA+Sham had similar behavioral aftereffects, only PA+Stim increased cortical excitability in M1 representations of the left upper and lower limb (toward the direction of the PA aftereffect), suggesting that PA+Stim may elicit greater neurophysiological changes and generalization to lower limb than PA alone.
Chagas Disease Screening: Awareness, Practices and Perceived Barriers Among Health Care Providers in Connecticut
Authors: Rayack Erica J. , Gutierrez-Torres Maria Alejandra , Lombo Bernardo , Mahoney-West Helen , Vermund Sten 
Published: October 2024

AbstractBackgroundAn estimated 288,000 people in the United States are infected with Chagas disease. Despite published recommendations for healthcare providers, the neglected nature of this disease persists, in part due to gaps in knowledge and low levels of Chagas disease awareness among healthcare providers. A survey was emailed to healthcare providers to assess knowledge of Chagas disease, screening practices, and provider-perceived barriers to screening.MethodsThe survey link was emailed to healthcare providers and department heads. Providers answered a series of questions categorized either as knowledge (K), practice (P), or perceived barriers (B), which were then scored by category. The analysis included Spearman’s rho test to measure the strength of the correlation coefficient between K and P scores and between K and B scores, Kruskal-Wallis tests to see if average K, P, and B scores were equal across specialty groups, and Pairwise Wilcoxon Rank Sum Tests to assess for a significant difference between average scores of cardiology, infectious disease, and the “other specialties” category.Results92 providers consented to complete the survey, 88 of whom fit the inclusion criteria of either affiliation with Yale University or YNHH. Infectious disease scored highest on average in knowledge and practices and reported lower provider-perceived barriers (0.66±0.183, 0.35±0.247, 0.42±0.365). No specialty received higher than 0.66±0.183 on average for knowledge or screening practices. Average perceived barriers to screening were highest in the “other” specialty category (0.76±0.303). There was a significant positive association between knowledge scores and screening practice scores and a significant negative association between knowledge scores and perceived barriers to screening.ConclusionsThis study revealed a knowledge deficit among healthcare providers in various specialties, which was associated with less frequent adherence to recommended screening practices for Chagas disease, as well as higher provider-perceived barriers to screening. This information can inform provider education initiatives so that patients at risk for Chagas disease may be better served in Connecticut and throughout the United States.
A novel patient-level computational model of atrial fibrillation patterns and clinical outcomes for evaluating screening strategies
Authors: Cai Minsi , Barrios-Espinosa Cristian , Rienstra Michiel , Crijns Harry J.G.M. , Schotten Ulrich , Heijman Jordi 
Published: October 2024

AbstractBackgroundThe dynamic, heterogenous nature of atrial fibrillation (AF) episodes and poor symptom-rhythm correlation make early AF detection challenging. The optimal screening strategy for early AF detection and its role in stroke prevention in different subpopulations are unknown. We developed a computational patient-level AF model able to simulate the dynamic occurrence of AF and AF-associated outcomes during the entire lifetime of a virtual patient cohort to elucidate the impact of AF screening in virtual randomized clinical trials (V-RCTs).MethodsThe Markov-like computer model has 7 clinical states (sinus rhythm, symptomatic/asymptomatic AF, each with/without previous stroke, and death). AF-related atrial remodeling was incorporated, which influenced the age-/sex-dependent transition probabilities between states. Model calibration/validation was performed by replicating a wide range of clinical studies. AF screening strategies and stroke rates in the presence of defined interventions were assessed in V-RCTs.ResultsThe model simulates the entire lifetime of virtual patients with minute-level resolution and provides perfect information on the occurrence of AF episodes and clinical outcomes (stroke, death). It replicates numerous age/sex-specific episode- and population-level AF metrics, including AF incidence/prevalence, progression rates, burden, episode duration, and stroke/mortality incidence. The benefits of intermittent AF screening in V-RCTs were frequency- and duration-dependent, with systematic thrice-daily single-ECG recordings providing the highest detection rates (64.6% of AF patients being diagnosed before their symptom-based clinical diagnosis). Screening groups had comparable 5-year stroke rates and lower 25-year stroke rates than the control group. These differences were increased by more effective anticoagulation therapy, in patients with higher baseline stroke risk, or in patients with delayed clinical AF diagnosis.ConclusionsWe present a novel computational patient-level AF model consistent with a large body of real-world data, enabling for the first time the systematic assessment of AF-management strategies. Screening protocols with more frequent and longer monitoring have higher AF-detection rates, but stroke reduction in screening-detected individuals is highly dependent on patients’ and healthcare-systems’ characteristics. V-RCTs suggest that frequent AF screening with effective anticoagulation can reduce stroke incidence in patients with high likelihood of delayed AF diagnosis.
Preserving Full Spectrum Information in Imaging Mass Spectrometry Data Reduction
Authors: Moens Roger A.R. , Migas Lukasz G. , Van Ardenne Jacqueline M. , Skaar Eric P. , Spraggins Jeffrey M. , Van de Plas Raf 
Published: October 2024

AbstractMotivationImaging mass spectrometry (IMS) has become an important tool for molecular characterization of biological tissue. However, IMS experiments tend to yield large datasets, routinely recording over 200,000 ion intensity values per mass spectrum and more than 100,000 pixels,i.e., spectra, per dataset. Traditionally, IMS data size challenges have been addressed by feature selection or extraction, such as by peak picking and peak integration. Selective data reduction techniques such as peak picking only retain certain parts of a mass spectrum, and often these describe only medium-to-high-abundance species. Since lower-intensity peaks and, for example, near-isobar species are sometimes missed, selective methods can potentially bias downstream analysis towards a subset of species in the data rather than considering all species measured.ResultsWe present an alternative to selective data reduction of IMS data that achieves similar data size reduction while better conserving the ion intensity profiles across all recordedm/z-bins, thereby preserving full spectrum information. Our method utilizes a low-rank matrix completion model combined with a randomized sparse-format-aware algorithm to approximate IMS datasets. This representation offers reduced dimensionality and a data footprint comparable to peak picking, but also retains complete spectral profiles, enabling comprehensive analysis and compression. We demonstrate improved preservation of lower signal-to-noise-ratio signals and near-isobars, mitigation of selection bias, and reduced information loss compared to current state-of-the art data reduction methods in IMS.
Epidermal microstructures on the paired fins of marine sculpins suggest new functional hypotheses supporting benthic station-holding
Authors: Kane Emily A. , Garner Austin M. , Yadav Shubham , Hume L. Ann , Pesacreta Tom 
Published: October 2024

AbstractHarsh environments, such as those with breaking waves and turbulent flows, present extreme challenges to organismal survival. Many animals exploiting these habitats possess adaptations to maintain position under dynamic flow conditions, such as reversible or permanent attachment systems. However, some station-holding fishes (e.g., sculpins) instead rely on morphological and behavioral modifications of their pectoral fins to increase friction with the substrate and combat drag. Despite epidermal microstructures on the fins of other benthic fishes, little exploration of pectoral fin surfaces at the microscopic scale has been undertaken in sculpins. Using scanning electron microscopy, we discovered microscopic, fibrillar projections contained within single cells on the ventral surfaces of the paired fin rays of two intertidal and two subtidal species of marine sculpins. In contrast to subtidal species, the intertidal species possessed epidermal cells with discrete channels separating groups of fibrillar projections. These features bear a striking resemblance to epidermal microstructures described in other fishes but have distinct morphological differences. We suggest the hypothesis that these previously overlooked features contribute to sculpin station-holding performance via enhanced mechanical interactions with the substrate, suggesting new taxa within which to explore potential mechanisms of underwater friction enhancement and adhesion.
SIRT4 enhances the cytotoxicity of NK cells toward hepatic stellate cells and reverses liver fibrosis via AMPKα/P-p53/NKG2DL pathway
Authors: Chen Huan , Da Binlin , Cai Zihao , Fang Rui , Xie Xiaolin , Zhang Han , Zhao Si , Zhang Ming , Wang Lei , Xu Bing , Zhuge Yuzheng , Zhang Feng 
Published: October 2024

AbstractNatural killer (NK) cells exhibit antifibrotic properties in liver fibrosis (LF) by suppressing activated hepatic stellate cells (HSCs). SIRT4, a mitochondrial regulatory protein, plays a crucial role as a link between energy metabolism and cell viability. However, the role of SIRT4 in the cytotoxicity of NK cells toward HSCs remains unexplored.In this study, we found that SIRT4 was markedly downregulated in both mouse models and patients with LF. The loss of SIRT4 reduced the cytotoxicity of NK cells against activated HSCs, while its overexpression enhanced this cytotoxicity. Mechanistically, SIRT4 activates AMPKα to promote p53 phosphorylation and facilitates its nuclear translocation, which induces the transcription of ULBP1 and ULBP2, members of the NK group 2D Legend (NKG2DL) family of molecules. Finally, overexpression of SIRT4 activated mouse hepatic NK cells and reversed LF by constructing adeno-associated viruses (AAV) that specifically target HSCs.Thus, SIRT4 is essential for the cytotoxicity of NK cells toward HSCs, and AAV8-pGAFP-SIRT4 may serve as a therapeutic approach for managing LF.Abstract Figure
Host specialization defines the emergence of new fungal plant pathogen populations
Authors: Fagundes Wagner C. , Hansen Rune , Rojas Barrera Idalia C. , Caliebe Frauke , Feurtey Alice , Haueisen Janine , Salimi Fatemeh , Alizadeh Alireza , Stukenbrock Eva H. 
Published: October 2024

AbstractHost-driven selection can be considered a strong driver of pathogen evolution. To successfully infect, colonize and complete their life cycle, plant pathogens are under constant selective pressures imposed by hosts, leading to genetic adaptation and possibly lineage radiation or speciation. Population and comparative genomics approaches are powerful tools to identify signatures of selection associated with host specialization in pathogen genomes and further allow recapturing population histories. Implementing such approaches, we identified evolutionary signatures of divergent host specialisation in distinct lineages of the fungal pathogenZymoseptoria tritici, a major disease causing-agent of wheat. Unique collections ofZ. triticiwere isolated from wild (Aegilopsspp.) and domesticated (Triticum aestivum) host grasses in the Middle East and whole-genome sequencing was performed in a selected subset of isolates from each collection. We observed distinct population structure between the two host-diverging pathogens and identified particular genomic features in theAegilops-infecting isolates that may have shaped their evolutionary history. Phylogenomic analyses revealed thatA. cylindricaandA. tauchii-infecting populations ofZ. triticiform separate clusters, possibly reflecting incipient speciation driven by divergent host specialization. Using infection experiments, we confirm thatZ. triticiisolates collected fromAegilopsspp. only infect their respective host species and notT. aestivum. Population genomics analyses and demographic inference furthermore allowed us to detect signatures of recent selection and show that divergence of the wheat-infecting lineage likely coincided with wheat domestication. At last, we confirm a virulence-related role for one candidate effector located in a selective sweep region of theA. cylindrica-infecting pathogen. Taken together, our findings highlight the interplay between agricultural and wild hosts on the evolution of fungal plant pathogens and illustrate host specialization as a possible route of rapid pathogen emergence.
Game Changing Mutation
Authors: Hellman Ziv , Edhan Omer 
Published: October 2024

AbstractWe present a model of the effect of mutation on haploid sexually reproducing populations by modelling the reproductive dynamics as occurring in the context of a common interests game played by the loci, with the alleles in the role of pure actions. Absent mutations, the population will deterministically converge to a pure Nash equilibrium of the game. A novel mutation adds new alleles, hence is tantamount to a change of the game by the addition of new actions. If the new game defined by the mutation removes the former pure Nash equilibrium the game changing mutation becomes in addition a Nash equilibrium changing mutation, as the population will then move to a new equilibrium with an increase in fitness. A graph of common interests games is defined, and evolution by mutation is modelled as a path through this graph.Short descriptionNovel mutation in sexual reproduction evolution modelled as population shifts between Nash equilibria in common interest games
BindCraft: one-shot design of functional protein binders
Authors: Pacesa Martin , Nickel Lennart , Schellhaas Christian , Schmidt Joseph , Pyatova Ekaterina , Kissling Lucas , Barendse Patrick , Choudhury Jagrity , Kapoor Srajan , Alcaraz-Serna Ana , Cho Yehlin , Ghamary Kourosh H. , Vinué Laura , Yachnin Brahm J. , Wollacott Andrew M. , Buckley Stephen , Westphal Adrie H. , Lindhoud Simon , Georgeon Sandrine , Goverde Casper A. , Hatzopoulos Georgios N. , Gönczy Pierre , Muller Yannick D. , Schwank Gerald , Swarts Daan C. , Vecchio Alex J. , Schneider Bernard L. , Ovchinnikov Sergey , Correia Bruno E. 
Published: October 2024

AbstractProtein–protein interactions (PPIs) are at the core of all key biological processes. However, the complexity of the structural features that determine PPIs makes their design challenging. We present BindCraft, an open-source and automated pipeline forde novoprotein binder design with experimental success rates of 10-100%. BindCraft leverages the weights of AlphaFold21to generate binders with nanomolar affinity without the need for high-throughput screening or experimental optimization, even in the absence of known binding sites. We successfully designed binders against a diverse set of challenging targets, including cell-surface receptors, common allergens,de novodesigned proteins, and multi-domain nucleases, such as CRISPR-Cas9. We showcase the functional and therapeutic potential of designed binders by reducing IgE binding to birch allergen in patient-derived samples, modulating Cas9 gene editing activity, and reducing the cytotoxicity of a foodborne bacterial enterotoxin. Lastly, we utilize cell surface receptor-specific binders to redirect AAV capsids for targeted gene delivery. This work represents a significant advancement towards a “one design-one binder” approach in computational design, with immense potential in therapeutics, diagnostics, and biotechnology.
Miniaturised laboratorial equipment as a solution to implement conservation genetics tools and education in West African countries with limited infrastructures: an application to the study of illegal wildlife trade in Guinea-Bissau
Authors: da Silva Maria Joana Ferreira , Colmonero-Costeira Ivo , Djaló Mohamed , Fernandes Nelson , Camará Tomás , Sá Rui M. , Minhós Tania , Kiebler Angelika , Grethlein Martin , Pikkarainen Netta , Prost Stefan 
Published: October 2024

AbstractIllegal wildlife trade (IWT) is considered one of the largest global illegal industries that negatively impacts biodiversity and sustainable development worldwide. DNA barcoding coupled with high-throughput sequencing has been shown to be useful in identifying taxa affected by IWT and has been routinely used during the last decades. However, for countries lacking laboratory infrastructures and sequencing units or trained staff, the application of DNA barcoding tools in conservation actions and policies is limited and dependent on slow sample export processes and molecular analyses carried out abroad. Guinea-Bissau (GB) is located on the West-African coast and has one of the lowest human development indices worldwide, while being a biodiversity hotspot facing many conservation challenges due to illegal commercial hunting, and trade in bushmeat and live individuals. Here, we explore the potential of using inexpensive and portable miniaturised laboratory equipment (MLE) to i) identify species illegally traded in GB using DNA barcoding methods and ii) to improve molecular biology and conservation genetic education and training in GB. Our overarching aim is to raise awareness of the current gap between the need to apply conservation genetic technologies in GB and the inability to do so due to a lack of laboratory infrastructures, sequencing units and opportunities for molecular biology training. We show that MLE can be a solution to accelerate the use of DNA barcoding methods to understand IWT and to train students, technicians and staff from governmental agencies dedicated to investigating environmental crimes, ultimately advancing the discipline of conservation genetics in the country.