bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating ECG Intervals from Lead-I Alone: External Validation of Supervised Models
Authors: Alam Ridwan , Stultz Collin M. 
Published: August 2024

AbstractThe diagnosis, prognosis, and treatment of a number of cardiovascular disorders rely on ECG interval measurements, including the PR, QRS, and QT intervals. These quantities are measured from the 12-lead ECG, either manually or using automated algorithms, which are readily available in clinical settings. A number of wearable devices, however, can acquire the lead-I ECG in an outpatient setting, thereby raising the potential for out-of-hospital monitoring for disorders that involve clinically significant changes in ECG intervals. In this work, we therefore developed a series of deep learning models for estimating the PR, QRS, and QT intervals using lead-I ECG. From a corpus of 4.2 million ECGs from patients at the Massachusetts General Hospital, we train and validate each of the models. At internal holdout validation, we achieve mean absolute errors (MAE) of 6.3 ms for QRS durations and 11.9 ms for QT intervals, and an MAE of 9.2 ms for estimating PR intervals. Moreover, as a well-defined P-wave does not always exist in ECG tracings – for example, when there is atrial fibrillation – we trained a model that can identify when there is a P-wave, and consequently, a measurable PR interval. We validate our models on three large external healthcare datasets without any finetuning or retraining - 3.2 million ECG from the Brigham and Women’s Hospital, 668 thousand from MIMIC-IV, and 20 thousand from PTB-XL - and achieve similar performance. Also, our models significantly outperform two publicly available baseline algorithms. This work demonstrates that ECG intervals can be tracked from only lead-I ECG using deep learning, and highlights the potential for out-of-hospital applications.
Cannabidiol for treatment of Irritability and Aggressive Behavior in Children and Adolescents with ASD: Background and Methods of the CAnnabidiol Study in Children with Autism Spectrum DisordEr (CASCADE) Study
Authors: Sannar Elise M. , Winter Joan R. , Franke Ronda K. , Werner Emily , Rochowiak Rebecca , Romani Patrick W. , Miller Owen S. , Bainbridge Jacquelyn L. , Enabulele Obehi , Thompson Talia , Natvig Crystal , Mikulich-Gilbertson Susan K. , Tartaglia Nicole R. 
Published: August 2024

ABSTRACTIntroductionAutism spectrum disorder (ASD) is a neurodevelopmental disorder commonly associated with behavioral challenges. There are few evidence based pharmacological interventions available for the treatment of behavioral symptoms associated with ASD. Cannabidiol (CBD), the non-psychoactive component of cannabis, has potential neuroprotective, antiepileptic, anxiolytic, and antipsychotic effects and may be useful in treating the behavioral symptoms of ASD.MethodsWe describe the research methods of a 27-week double-blind placebo-controlled cross-over trial of cannabidiol for the treatment of irritability and aggression associated with ASD, utilizing the irritability subscale of the Aberrant Behavior Checklist-2nd edition (ABC-2) as the primary outcome measure. Adverse effects and safety monitoring protocols are included. Several secondary and exploratory outcomes measures also include anxiety, communication, repetitive behaviors, attention, hyperactivity, autism family experience, and telehealth functional behavior assessment.ConclusionThere is a significant need for clinical research exploring alternative medications for the treatment of behavioral symptoms of ASD. Cannabidiol (CBD) is being studied for the management of irritability, aggression, and other problem behaviors associated with ASD.
Comparison of ChatGPT and Gemini as sources of references in otorhinolaryngology
Authors: Jędrzejczak W. Wiktor , Pastucha Małgorzata , Skarżyński Henryk , Kochanek Krzysztof 
Published: August 2024

AbstractIntroductionAn effective way of testing chatbots is to ask them for references since such items can be easily verified. The purpose of this study was to compare the ability of ChatGPT-4 and Gemini Advanced to select accurate references on common topics in otorhinolaryngology.MethodsChatGPT-4 and Gemini Advanced were asked to provide references on 25 topics within the otorhinolaryngology category of Web of Science. Within each topic, we set as target the most cited papers which had “guidelines” in the title. The chatbot responses were collected on three consecutive days to take into account possible variability. The accuracy and reliability of the provided references were evaluated.ResultsAcross the three days, the accuracy of ChatGPT-4 was 29–45% while that of Gemini Advanced was 10–17%. Common errors included false author names, false DOI numbers, and incomplete information. Lower percentage errors were associated with higher number of citations.ConclusionsBoth chatbots performed poorly in finding references, although ChatGPT-4 provided higher accuracy than Gemini Advanced.
Urinary multi-omics reveal non-invasive diagnostic biomarkers in clear cell renal cell carcinoma
Authors: Jonsson Gustav , Hofmann Maura , Oliveira Tiago , Lemberger Ursula , Stejskal Karel , Krššáková Gabriela , Sakic Irma , Novatchkova Maria , Mereiter Stefan , Grabmann Gerlinde , Köcher Thomas , Kikic Zeljko , Rechberger Gerald N. , Züllig Thomas , Englinger Bernhard , Schmidinger Manuela , Penninger Josef M. 
Published: August 2024

AbstractClear cell renal cell carcinoma (ccRCC) is the kidney malignancy with the highest incidence and mortality rates. Despite the high patient burden, there are no biomarkers for rapid diagnosis and public health surveillance. Urine would be an ideal source of ccRCC biomarkers due to the low invasiveness, easy accessibility, and the kidney’s intrinsic role in filtering urine. In the present work, by combining proteomics, lipidomics and metabolomics, we detected urogenital metabolic dysregulation in ccRCC patients with increased lipid metabolism, altered mitochondrial respiration signatures and increased urinary lipid content. Importantly, we identify three early-stage diagnostic biomarkers for ccRCC in urine samples: Serum amyloid A1 (SAA1), Haptoglobin (HP) and Lipocalin 15 (LCN15). We further implemented a parallel reaction monitoring mass spectrometry protocol for rapid and sensitive detection of SAA1, HP and LCN15 and combined all three proteins into a diagnostic UrineScore. In our discovery cohort, this score had a performance accuracy of 96% in receiver operating characteristic curve (ROC) analysis for classification of ccRCC versus control cases. Our data identifies tractable and highly efficacious urinary biomarkers for ccRCC diagnosis and serve as a first step towards the development of more rapid and accessible urinary diagnostic platforms.
Genome-wide Association Study of Rice Vegetative Biomass under Different Inorganic Nitrogen Forms — Ammonium or Nitrate
Authors: Kasemsap Pornpipat , Cohen Itay , Bloom Arnold J. 
Published: August 2024

AbstractRice is the most important source of daily calories in human diets and second only to wheat as the most important protein source. Rice is generally exposed to high ammonium (NH4+) levels in the rhizosphere but may employ both NH4+and nitrification-derived nitrate (NO3-) as major sources of nitrogen. However, the genetic basis underlying rice adaptation to different nitrogen forms remains poorly characterized. Here, we assessed biomass under either NH4+or NO3-as a sole nitrogen source in 390 accessions from the USDA Rice Diversity Panel 1. Rice effectively used either form of nitrogen to support early growth. Tolerance to a high-NH4+exposure was correlated with biomass under NO3-and lower NH4+levels. Both genotype and nitrogen source strongly influenced biomass accumulation and partitioning between shoot and root. Root showed the greatest biomass variability and sensitivity to nitrogen source. Genome-wide analyses identified 176 single nucleotide polymorphism (SNP) markers associated with biomass across the full diversity panel and individual populations. The majority of the associations were unique to the individual nitrogen source. We compiled a list of candidate genes, including putative genes involved in nitrogen metabolism, located within 150 kb of 112 most significant SNPs, each with at least 3 adjacent markers detected under the same combination of population and nitrogen source. A flexible consumer, rice may employ distinct genetic mechanisms to use different nitrogen sources, making the species more resilient to fluctuations in soil nitrogen. These insights can guide matching rice genotypes with fertilizer management to improve nitrogen-use efficiency.
A conserved regulation of cell expansion underlies notochord mechanics, spine morphogenesis, and endochondral bone lengthening
Authors: Voigt Brittney , Frazier Katherine , Yazdi Donya , Gontarz Paul , Zhang Bo , Sepich Diane S. , Solnica-Krezel Lilianna , Gray Ryan S. 
Published: August 2024

SUMMARYCell size is a key contributor to tissue morphogenesis1. As a notable example, growth plate hypertrophic chondrocytes use cellular biogenesis and disproportionate fluid uptake to expand 10-20 times in size to drive lengthening of endochondral bone2,3. Similarly, notochordal cells expand to one of the largest cell types in the developing embryo to drive axial extension4–6. In zebrafish, the notochord vacuolated cells undergo vacuole fusion to form a single large, fluid-filled vacuole that fills the cytoplasmic space and contributes to vacuolated cell expansion7. When this process goes awry, the notochord lacks sufficient hydrostatic pressure to support vertebral bone deposition resulting in adult spines with misshapen vertebral bones and scoliosis8. However, it remains unclear whether endochondral bone and the notochord share common genetic and cellular mechanisms for regulating cell and tissue expansion. Here, we demonstrate that the 5’-inositol phosphatase gene,inppl1a, regulates notochord expansion, spine morphogenesis, and endochondral bone lengthening in zebrafish. Furthermore, we show thatinppl1aregulates notochord expansion independent of vacuole fusion, thereby genetically decoupling these processes. We demonstrate thatinppl1a-dependent notochord expansion is essential to establish normal mechanical properties of the notochord to facilitate the development of a straight spine. Finally, we find thatinppl1ais also important for endochondral bone lengthening in fish, as has been shown in the humanINPPL1-related endochondral bone disorder, Opsismodysplasia9. Overall, this work reveals a conserved mechanism of cell size regulation that influences disparate tissues critical for skeletal development and short-stature disorders.
Serotonin neuromodulation directs optic nerve regeneration
Authors: Saied-Santiago Kristian , Baxter Melissa , Mathiaparanam Jaffna , Granato Michael 
Published: August 2024

AbstractOptic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro- regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find several serotonin type-1 receptor genes are expressed in RGC neurons during regeneration and that inhibiting 5- HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is critical for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo.Summary Statement5-HT1 receptors selectively promote early optic nerve regrowth in zebrafish but are dispensable during development. Serotonin receptor-dependent modulation instructs regenerating optic nerve axons toward the brain in vivo.
Stochastic Character Mapping of Continuous Traits on Phylogenies
Authors: Martin B. S. , Weber M. G. 
Published: August 2024

AbstractLiving and fossilized organisms represent only a tiny fraction of Earth’s evolutionary history, motivating “ancestral state reconstruction” techniques that aim to infer the unobserved phenotypes of evolving lineages based on measurements of their relatives. Stochastic character mapping (“simmapping”) methods perform ancestral state reconstruction by randomly sampling maps (“simmaps”) of probable phenotypic evolutionary histories along phylogenies, allowing researchers to conveniently and flexibly analyze macroevolutionary patterns and processes while accounting for the inherent uncertainty of ancestral state estimates. Here, we introduce a flexible and efficient algorithm for simmapping continuous phenotypes evolving under Brownian Motion models, which we term continuous simmaps or “contsimmaps”, thereby generalizing existing simmapping methods which only work with discrete phenotypes. To demonstrate potential applications of contsimmaps, we develop a pipeline that uses contsimmaps to test for associations between rates of continuous trait evolution and continuously-varying factors (e.g., generation time, climatic niche)–a difficult statistical problem for which few methods are currently available. Through an extensive simulation study, we show that this novel pipeline can accurately and robustly infer factor-rate relationships from phylogenetic comparative data, albeit with low power under certain conditions. Lastly, we apply this pipeline to an empirical dataset, showing that rates of leaf and flower trait evolution are highly variable yet unrelated to height in a clade of eucalyptus trees spanning roughly 1 to 100 meters in maximum height. Ultimately, contsimmaps provide a valuable new tool for macroevolutionary biology by allowing researchers to more flexibly analyze the evolutionary dynamics of continuous phenotypes and test complex evolutionary hypotheses involving continuous variables.
Real-time identification of carbapenemase-producingKlebsiella pneumoniaelineages and outbreak detection using FT-IR ATR
Authors: Gonçalves Ana Beatriz , Alves Valquíria , Neves Isabel , Read Maria Antónia , Pinheiro Natália , Henius Anna Emilie , Hasman Henrik , Peixe Luísa , Novais Ângela 
Published: August 2024

AbstractExpansion of carbapenemase-producingKlebsiella pneumoniae(CP-Kp) is driven by nosocomial dissemination, and effective infection control depends on timely and reliable typing data. Here, we evaluated our previously developed Fourier-transform infrared spectroscopy (FT-IR) with attenuated total reflectance (ATR) workflow for real-time typing ofKpcapsular (KL)-types and lineages to support infection control. FT-IR spectra were acquired from Columbia agar with 5% sheep blood cultures of all CP-Kpinfection isolates (n=136) from hospitalized patients at a northern Portugal hospital (April 2022 – March 2023), and analyzed using automated machine-learning (ML) classification models. Typing results were confirmed bywzisequencing, MLST and/or WGS. FT-IR typing on Columbia agar plates showed 73% sensitivity, 79% specificity and 74% accuracy. Our method correctly typed 94% of typeable isolates (78/83), from which 87% were comunicated in <24h. Sixty percent of non-typeable isolates were considered false negatives, but the majority (66%) was correctly predicted when re-tested in Mueller-Hinton agar, improving sensitivity (92%), specificity (76%) and accuracy (89%) ofKptyping. ThreeKplineages (ST147-KL64, ST15-KL19, ST268-KL20) represented 74% of the sample, with ST268-KL20 causing an outbreak in Neonatal Intensive Care unit, quickly recognized by FT-IR enabling immediate infection control measures. Epidemiological links between patiens were mostly found on medical, surgical and urology units, using EpiLinx software. Most isolates (98%) produced KPC-3. Our FT-IR ATR ML-based typing workflow demonstrated high performance standards in real-time and high adaptability to clonal dynamics. The unprecedent time-to-response (same day of species identification) represents an opportunity to implement timely and effective infection control measures.ImportanceThis study represents the first prospective and real-time evaluation of FT-IR spectroscopy to type multidrug resistantKlebsiella pneumoniaeto support surveillance and infection control. We demonstrate a high sensitivity, specificity and accuracy of a previously developed workflow that allows precise identification ofK. pneumoniaelineages. The adaptability to changes in clonal dynamics and bacterial typing in <24h offer significant advantages in both high- and low-income countries for a timely infection control and improvement of antimicrobial resistance management.
Bovine highly pathogenic avian influenza virus stability and inactivation in the milk byproduct lactose
Authors: Kwon Taeyong , Gebhardt Jordan T. , Lyoo Eu Lim , Nooruzzaman Mohammed , Gaudreault Natasha N. , Morozov Igor , Diel Diego G. , Richt Juergen A. 
Published: August 2024

AbstractA bovine isolate of highly pathogenic avian influenza H5N1 virus was stable for 14 days in a concentrated lactose solution at under refrigerated conditions. Heat or citric acid treatments successfully inactivated viruses in lactose. This study highlights the persistence of HPAIV in lactose and its efficient inactivation under industrial standards.
Arp2/3 iso-complexes limit t-tubule overgrowth to ensure myofiber formation and synchronous contraction
Authors: Pereira Ana Raquel , Soares Ana da Rosa , Liu Tianyang , Ferreira Josie Liane , Leal Graciano , Faleiro Inês , Kogata Naoko , Way Michael , Moores Carolyn A. , Gomes Edgar R. 
Published: August 2024

SummaryT-tubules are long plasma membrane invaginations that form contact sites with two adjacent endoplasmic reticulum compartments to generate a skeletal muscle triad. Although the importance of t-tubules is well established, and abnormalities are found in multiple muscle disorders, the mechanisms of t-tubule growth are currently unknown. We found that the branched actin nucleator Arp2/3 regulates t-tubule organisation in myofibers. Cortical actin limits t-tubule growth, suggesting that it must be locally disassembled to allow the t-tubule to grow. T-tubule overgrowth is limited by Arpc5-containing Arp2/3 iso-complexes, but not those containing Arpc5L. Loss of Arpc5 results in malformed t-tubule clusters, impaired triads, and asynchronous muscle contraction, as found in multiple muscle disorders. Therefore, limiting t-tubule overgrowth has a role in triad formation and myofiber contraction, providing a possible pathophysiological mechanism for these muscle disorders.Graphical abstract
Pharmacological GCase Activity Enhancement Inhibits Tau Accumulation
Authors: Ciccaldo Matteo , Pérez-Carmona Natàlia , Piovesana Ester , Cano-Crespo Sara , Ruano Ana , Delgado Aida , Fregno Ilaria , Guzmán Beatriz Calvo-Flores , Bellotto Manolo , Molinari Maurizio , Taylor Joanne , Papin Stéphanie , García-Collazo Ana María , Paganetti Paolo 
Published: August 2024

AbstractA slow decline in the autophagy-lysosomal pathway is a hallmark of the normal aging brain. Yet, an acceleration of this cellular function may propel neurodegenerative events. In fact, mutations in genes associated with the autophagy-lysosomal pathway can lead to Parkinson’s disease. Also, amyloidogenic protein deposition is observed in lysosomal storage disorders, which are caused by genetic mutations representing risk factors for Parkinson’s disease. For example, Gaucher’s diseaseGBA1mutations leading to defects in lysosomal sphingolipid metabolism cause α-synuclein accumulation. We observed that increased lysosomal Tau accumulation is found in human dermal fibroblasts engineered for inducible Tau expression. Inhibition of theGBA1product GCase augmented Tau-dependent lysosomal stress and Tau accumulation. Here, we show increased Tau seed-induced Tau accumulation in Gaucher’s fibroblasts carryingGBA1mutations when compared to normal fibroblasts. Pharmacological enhancement of GCase reversed this effect, notably, also in normal fibroblasts. This suggests that boosting GCase activity may represent a therapeutic strategy to slow down aging-dependent lysosomal deficits and brain protein deposition.
A comparative analysis of job satisfaction prediction models using machine learning: a mixed-method approach
Authors: Kim Jaekyeong , Chang Pil-Sik , Yang Sung-Byung , Choi Ilyoung , Lee Byunghyun 
Published: August 2024

PurposeBecause the food service industry is more dependent on customer contact and human resources than other industries, it is crucial to understand the factors influencing employee job satisfaction to ensure that employees provide satisfactory service to customers. However, few studies have incorporated employee reviews of job portals into their research. Many job seekers tend to trust company reviews posted by employees on job portals based on the information provided by the company itself. Thus, this study utilized company reviews and job satisfaction ratings from employees in the food service industry on a job portal site, Job Planet, to conduct mixed-method research.Design/methodology/approachFor qualitative research, we applied the Latent Dirichlet Allocation (LDA) model to food service industry company reviews to identify 10 job satisfaction factors considered important by employees. For quantitative research, four algorithms were used to predict job satisfaction ratings: regression tree, multilayer perceptron (MLP), random forest and XGBoost. Thus, we generated predictor variables for six cases using the probability values of topics and job satisfaction ratings on a five-point scale through LDA and used them to build prediction algorithms.FindingsThe analysis showed that algorithm accuracy performed differently in each of the six cases, and overall, factors such as work-life balance and work environment have a significant impact on predicting job satisfaction ratings.Originality/valueThis study is significant because its methodology and results suggest a new approach based on data analysis in the field of human resources, which can contribute to the operation and planning of corporate human resources management in the future.