bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ANI‐2 enabled open‐source protocol to estimate ligand strain after docking
Authors: Berenger Francois , Tsuda Koji 
Published: October 2024

AbstractIn protein‐ligand docking, the score assigned to a protein‐ligand complex is approximate. Especially, the internal energy of the ligand is difficult to compute precisely using a molecular mechanics based force‐field, introducing significant noise in the rank‐ordering of ligands. We propose an open‐source protocol (https://github.com/UnixJunkie/MMO), using two quantum mechanics (QM) single point energy calculations, plus a Monte Carlo (Monte Carlo) based ligand minimization procedure in‐between, to estimate ligand strain after docking. The MC simulation uses the ANI‐2x (QM approximating) force field and is performed in the dihedral space. On some protein targets, using strain filtering after docking allows to significantly improve hit rates. We performed a structure‐based virtual screening campaign on nine protein targets from the Laboratoire d'Innovation Thérapeutique—PubChem assays dataset using Cambridge crystallographic data centre genetic optimization for ligand docking. Then, docked ligands were submitted to the strain estimation protocol and the impact on hit rate was analyzed. As for docking, the method does not always work. However, if sufficient active and inactive molecules are known for a given protein target, its efficiency can be evaluated.
Clustering Based on Laboratory Data in Patients With Heart Failure Admitted to the Intensive Care Unit
Authors: Nemati Sepehr , Mohammadi Babak , Hooshanginezhad Zahra 
Published: October 2024

ABSTRACTBackgroundHeart failure (HF) is a common condition that imposes a significant burden on healthcare systems. We aimed to identify subgroups of patients with heart failure admitted to the ICU using routinely measured laboratory biomarkers.MethodsA large dataset (N = 1176) of patients with heart failure admitted to the ICU at the Beth Israel Deaconess Medical Center in Boston, USA, between June 1, 2001, and October 31, 2012, was analyzed. We clustered patients to identify laboratory phenotypes. Cluster profiling was then performed to characterize each cluster, using a binary logistic model.ResultsTwo distinct clusters of patients were identified (N = 679 and 497). There was a significant difference in the mortality rate between Clusters 1 and 2 (50 [7.4%] vs. 109 [21.9%], respectively, p < 0.001). Patients in the Cluster 2 were significantly older (mean [SD] age = 72.35 [14.40] and 76.37 [11.61] years, p < 0.001) with a higher percentage of chronic kidney disease (167 [24.6%] vs. 262 [52.7%], respectively, p < 0.001). The logistic model was significant (Log‐likelihood ratio p < 0.001, pseudo R2 = 0.746) with an area under the curve of 0.905. The odds ratio for leucocyte count, mean corpuscular volume (MCV), red blood cell (RBC) distribution width, hematocrit (HcT), lactic acid, blood urea nitrogen (BUN), serum potassium, magnesium, and sodium were significant (all p < 0.05).ConclusionLaboratory data revealed two phenotypes of ICU‐admitted patients with heart failure. The two phenotypes are of prognostic importance in terms of mortality rate. They can be differentiated using blood cell count, kidney function status, and serum electrolyte concentrations.
Is intermediate risk really intermediate? Comparison of karyotype and non‐invasive prenatal testing results of pregnancies at intermediate risk of trisomy 21 on maternal serum screening
Authors: Alkan Bulbul Gul , Kirtis Emine , Kandemir Hulya , Sanhal Cem Yasar , Yakut Uzuner Sezin , Karauzum Sibel Berker , Mendilcioglu Ibrahim Inanc 
Published: October 2024

AbstractThe purpose of this study was to assess the additional contribution of karyotyping compared with genome‐wide non‐invasive prenatal testing (NIPT) for pregnancies at intermediate risk for trisomy 21 (T21), calculated using the maternal serum screening without major structural anomalies detected through sonography. Karyotype results of all pregnancies undergoing invasive prenatal diagnostic testing between January 2013 and March 2022 were obtained from a large hospital‐based laboratory. Pregnancies with no major structural anomalies on ultrasound (including soft markers) and an intermediate risk for T21 on maternal serum screening were included in this study. The additional contribution of karyotyping for abnormal karyotype results was calculated after excluding results that could theoretically be identified with genome‐wide NIPT. Among the 511 pregnancies analyzed, 13 (2.54%) were found to have abnormal karyotype results, 9 (1.76%) of which could theoretically have been detected with genome‐wide NIPT. Within the cohort, 6/263 (2.28%) of women aged 35 years and older, and 3/248 (1.20%) of women younger than 35 years had results that could have been detected with genome‐wide NIPT. After excluding results detectable using genome‐wide NIPT, the additional contribution of karyotyping was found as 4/502 (0.79%) for the entire cohort, 2/257 (0.77%) for women aged 35 years and older, 2/245 (0.81%) for women younger than 35 years. Of the 511 examined pregnancies at intermediate risk for T21 by maternal serum screening, genome‐wide NIPT would have failed to detect 4 of 13 abnormal karyotype results. The findings hold importance in guiding couples' informed decision‐making processes regarding their choice of genetic screening and diagnostic testing in case of intermediate risk for T21.
VEXAS without vacuoles: Linking genotype to phenotype
Authors: Zhukovsky Sara , Rets Anton , Braaten Tawnie , Patel Ami B. 
Published: October 2024

AbstractIntroductionVEXAS syndrome is a rare condition characterized by somatic mutations in the ubiquitin‐like modifier activating enzyme 1 (UBA1) gene and a constellation of clinical/morphologic findings, including the presence of cytoplasmic vacuoles within bone marrow hematopoietic cells.Methods and objectivesIn this report, we present a case of a male patient diagnosed with VEXAS‐associated myelodysplastic syndrome following the detection of a non‐canonical UBA1 p.Gly477Ala variant whose bone marrow biopsy revealed a conspicuous absence of cytoplasmic vacuolization in hematopoietic cells. This case prompts a comprehensive review of the existing literature on the significance and pathobiology of vacuolization in the context of VEXAS and UBA1 mutations.
Clinical outcomes during and after wearable cardioverter defibrillator use in Japanese patients with heart failure: A single‐center experience
Authors: Kikuchi Noriko , Shiga Tsuyoshi , Sugawara Yohei , Suzuki Atsushi , Minami Yoshiaki , Hattori Hidetoshi , Shoda Morio , Hagiwara Nobuhisa , Yamaguchi Junichi 
Published: October 2024

AbstractBackgroundA wearable cardioverter defibrillator (WCD) is indicated for a limited period in patients at high risk of sudden cardiac death (SCD). Nonischemic heart failure (HF) is common among Japanese patients with HF. The aim of this study was to evaluate the incidence of fatal arrhythmias during WCD use and the clinical outcomes after WCD withdrawal in Japanese patients with HF.MethodsWe retrospectively studied 105 hospitalized HF patients who were discharged with a WCD. The main outcome was SCD/ventricular arrhythmias during WCD use and the other outcomes were implantation of an implantable cardioverter‐defibrillator (ICD), SCD/ventricular arrhythmias after WCD withdrawal, and changes in left ventricular ejection fraction (LVEF).ResultsEighty‐seven (83%) patients received a WCD for primary prevention of SCD, of whom 60 (69%) were new‐onset HF patients with an LVEF ≤35%. The median daily wear time was 22.1 h. Two patients experienced sustained ventricular tachycardia and one patient experienced atrioventricular block with asystole while on WCD. After WCD withdrawal, 81 (77%) patients decided not to receive ICD implantation. The percentage of patients with an LVEF ≥35% increased from 20% at baseline to 70% at 1 year after discharge. During the median follow‐up of 50 months, 78 (96%) of the 81 patients who did not have an ICD were free of SCD/ventricular arrhythmias.ConclusionsThe use of a WCD is useful for determining the appropriate indication for ICD implantation in Japanese patients with new‐onset HF, a low LVEF, and a risk of SCD.
Active Ingredient Prescribing in Australia: exploring pharmacists' experiences
Authors: Swifte Taylah , Bowden Michelle , Ndukwe Henry 
Published: October 2024

AbstractBackgroundThe Active Ingredient Prescribing (AIP) mandate was introduced Australia‐wide on 1 February 2021. The AIP legislation makes the pharmacist a stakeholder who can provide valuable information to customers and patients.AimTo explore the experiences of community pharmacists with AIP legislation with a focus on attitude, health literacy, and medication safety.MethodSemi‐structured, in‐depth interviews were conducted and guided by the Theoretical Domains Framework (TDF). Transcripts were analysed using a deductive approach to categorise data and inductive thematic analysis to identify concepts and themes. Ethical approval was granted by the Griffith University Human Research Ethics Committee (Reference no: 2021/878) and the study conforms to the Australian National Statement on Ethical Conduct in Human Research. Informed consent from all participants was obtained via a study information sheet distributed to all potential participants and completion of written consent forms prior to participation in the study. Participants received gift cards as compensation for their time.ResultsSix pharmacists participated, and thematic analysis of collected data revealed three main themes. These included education, integration, and trust. Insights on patients' acceptance of their prescriptions and the expanded patient‐facing opportunities were highlighted. Participants' opinions leaned towards enhancing the smooth integration into the AIP process of other stakeholders like prescribers and regulatory bodies. Establishing multilevel communication between stakeholders and customers was pivotal to improving health literacy and medication safety. Pharmacists' views on process integration provided unique insight into the practical challenges with the AIP mandate. In addition, ‘trust’ in the prescriber enhanced patient acceptance of generic medicines.ConclusionThe study provided baseline evidence to show that the AIP mandate enhances health literacy and empowers patients to know the active ingredients in their medicines, which in turn supports medication safety. Examining the implementation of the AIP legislation facilitated a nuanced understanding of the effect that these AIP changes have on patients.
Matrix Isolation FT‐Raman Study of Acetylacetone D2‐Acetylacetone and Hexafluoroacetylacetone
Authors: Gutiérrez‐Quintanilla Alejandro , Platakyte Rasa , Chevalier Michèle , Crépin Claudine , Ceponkus Justinas 
Published: October 2024

ABSTRACTAcetylacetone, double‐deuterated acetylacetone and hexafluoroacetylacetone were isolated in inert matrices and investigated by means of Raman scattering and infrared absorption spectroscopic methods, combined with theoretical calculations. The ability of Raman spectroscopy to access low wavenumber modes enables the study of vibrational modes involved in internal hydrogen bonds that are challenging to observe with infrared absorption spectroscopy. An almost complete set of vibrational modes for the studied molecules was observed experimentally, facilitating a comprehensive assessment of different computational approaches. The large dataset obtained allowed for an improved assignment of vibrational bands and firmly confirmed the existence of only one chelated isomer of acetylacetone, double‐deuterated acetylacetone and hexafluoroacetylacetone in matrices. The experimental data also highlighted the effects of deuteration and fluorination.
Spray dried protein concentrates from white button and oyster mushrooms produced by ultrasound‐assisted alkaline extraction and isoelectric precipitation
Authors: de Medeiros Fábio Gonçalves Macêdo , You Seung Woon , Hoskin Roberta Targino , Moncada Marvin 
Published: October 2024

AbstractBACKGROUNDIn the present study, the optimization of ultrasound‐assisted alkaline extraction (UAAE) and isoelectric precipitation (IEP) was applied to white button (WBM) and oyster (OYM) mushroom flours to produce functional spray dried mushroom protein concentrates. Solid‐to‐liquid ratio (5–15% w/v), ultrasound power (0–900 W) and type of acid [HCl or acetic acid (AcOH)] were evaluated for their effect on the extraction and protein yields from mushroom flours submitted to UAAE‐IEP protein extraction.RESULTSPrioritized conditions with maximized protein yield (5% w/v, 900 W, AcOH, for WBM; 5% w/v, 900 W, HCl for OYM) were used to produce spray dried protein concentrates from white button (WBM‐PC) and oyster (OYM‐PC) mushrooms with high solids recovery (62.3–65.8%). WBM‐PC and OYM‐PC had high protein content (5.19–5.81 g kg−1), in addition to remarkable foaming capacity (82.5–235.0%) and foam stability (7.0–162.5%), as well as antioxidant phenolics. Highly pH‐dependent behavior was observed for solubility (> 90%, at pH 10) and emulsifying properties (emulsification activity index: > 50 m2 g−1, emulsion stability index: > 65%, at pH 10). UAAE‐IEP followed by spray drying increased surface hydrophobicity and free sulfhydryl groups by up to 196.5% and 117.5%, respectively, which improved oil holding capacity (359.9–421.0%) and least gelation concentration (6.0–8.0%) of spray dried mushroom protein concentrates.CONCLUSIONOverall, the present study showed that optimized UAAE‐IEP coupled with spray drying is an efficient strategy to produce novel mushroom protein concentrates with enhanced functional attributes for multiple food applications. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Spatial distribution projections of suitable environmental conditions for key Baltic Sea zooplankton species
Authors: Serandour Baptiste , Blenckner Thorsten , Jan Kinlan M. G. , Leroy Boris , Ramiro‐Sánchez Berta , Campbell Eleanore , Winder Monika 
Published: October 2024

AbstractEnvironmental changes reshape biological communities, inducing cascading effects throughout the food webs. These changes pressure species either to adapt or to track favorable habitats. Estuaries represent an interesting case study to investigate such responses as species will rapidly reach physical boundaries if they cannot adapt fast enough and need to track suitable conditions. One such estuary is the Baltic Sea, characterized by a salinity and temperature gradient that shapes species distribution and imposes physiological stress on organisms. The Baltic Sea is projected to be affected by substantial modifications in environmental conditions by the end of the 21st century, which could have major consequences for species distribution and community composition. However, despite the impending changes and their potential impact, there is a gap in understanding the potential consequences on pelagic species of the Baltic Sea. This study employs long‐term observations of primary zooplankton species in the pelagic food web to model changes in their distribution under future climate projections. We found that the parameters having the largest influence on habitat suitability varied across species, although maximal temperature was the most important for six out of seven species. In addition, there was a shrinkage of suitable area for several key species driven by a decrease in salinity and a rise in water temperature. We discuss the complex interplay between environmental changes and the spatial distribution of pelagic species in the Baltic Sea, highlighting the need for proactive management strategies to mitigate potential ecological impacts in the face of future climate scenarios.
Quantitative Tractography‐Based Evaluations in Essential Tremor Patients after MRgFUS Thalamotomy
Authors: Ghielmetti Francesco , Aquino Domenico , Golfrè Andreasi Nico , Mazzi Federica , Greco Elena , Cilia Roberto , De Martin Elena , Rinaldo Sara , Stanziano Mario , Levi Vincenzo , Braccia Arianna , Marchetti Marcello , Fumagalli Maria L. , Demichelis Greta , Colucci Fabiana , Romito Luigi Michele , Devigili Grazia , Elia Antonio E. , Caldiera Valentina , Verri Mattia , Ciceri Elisa Francesca , Di Meco Francesco , Grisoli Marina , Bruzzone Maria Grazia , Eleopra Roberto 
Published: October 2024

AbstractBackgroundMagnetic resonance‐guided focused ultrasound (MRgFUS) targeting the thalamic ventral intermediate nucleus (VIM) is an innovative treatment for drug‐refractory essential tremor (ET). The relationship between lesion characteristics, dentate‐rubro‐thalamic‐tract (DRTT) involvement and clinical benefit remains unclear.ObjectivesTo investigate whether clinical outcome is related to lesion volume and/or its overlap with the DRTT. To compare the reliability of probabilistic versus deterministic tractography in reconstructing the DRTT and improving VIM targeting.MethodsForty ET patients who underwent MRgFUS thalamotomy between 2019 and 2022 were retrospectively analyzed. Clinical outcomes and adverse effects were recorded at 1/6/12 months after the procedure. The DRTT was generated using deterministic and probabilistic tractography on preoperative diffusion‐tensor 3 T‐images and location and volume of the lesion were calculated.ResultsProbabilistic tractography identified both decussating (d‐DRTT) and non‐decussating (nd‐DRTT) components of the DRTT, whereas the deterministic approach only identified one component overlapping with the nd‐DRTT. Despite the lesions predominantly intersecting the medial portion of the d‐DRTT, with a significantly greater overlap in responder patients, we observed only a non‐significant correlation between tremor improvement and increased d‐DRTT‐lesion overlap (r = 0.22, P = 0.20). The lesion volume demonstrated a significant positive correlation with clinical improvement at 1‐day MRI (r = 0.42, P < 0.01).ConclusionVariability in the reconstructed DRTT position relative to the lesion center of mass, even among good responders, suggests that this fiber bundle is unlikely to be considered the sole target for a successful MRgFUS thalamotomy in ET. Indirect individualized targeting allows for more precise and reproducible identification of actual treatment coordinates than the direct method.
The endocrine manifestations of adults with spinal muscular atrophy
Authors: Rakusa Matej , Koritnik Blaž , Leonardis Lea , Goricar Katja , Rudolf Tjasa , Firbas Dejan , Snoj Žiga , Jensterle Mojca 
Published: October 2024

AbstractIntroduction/AimsChanges in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA.MethodsThe cross‐sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30–51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin‐like growth factor‐1 (IGF‐1). Blood glucose, insulin, and beta‐hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated.ResultsIn total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF‐1 negatively correlated with FM.DiscussionAdult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.
Fractal dimension and lacunarity measures of glioma subcomponents are discriminative of the grade of gliomas and IDH status
Authors: Yadav Neha , Mohanty Ankit , V Aswin , Tiwari Vivek 
Published: October 2024

AbstractSince the overall glioma mass and its subcomponents—enhancing region (malignant part of the tumor), non‐enhancing (less aggressive tumor cells), necrotic core (dead cells), and edema (water deposition)—are complex and irregular structures, non‐Euclidean geometric measures such as fractal dimension (FD or “fractality”) and lacunarity are needed to quantify their structural complexity. Fractality measures the extent of structural irregularity, while lacunarity measures the spatial distribution or gaps. The complex geometric patterns of the glioma subcomponents may be closely associated with the grade and molecular landscape. Therefore, we measured FD and lacunarity in the glioma subcomponents and developed machine learning models to discriminate between tumor grades and isocitrate dehydrogenase (IDH) gene status. 3D fractal dimension (FD3D) and lacunarity (Lac3D) were measured for the enhancing, non‐enhancing plus necrotic core, and edema‐subcomponents using preoperative structural‐MRI obtained from the The Cancer Genome Atlas (TCGA) and University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF‐PDGM) glioma cohorts. The FD3D and Lac3D measures of the tumor‐subcomponents were then compared across glioma grades (HGGs: high‐grade gliomas vs. LGGs: low‐grade gliomas) and IDH status (mutant vs. wild type). Using these measures, machine learning platforms discriminative of glioma grade and IDH status were developed. Kaplan–Meier survival analysis was used to assess the prognostic significance of FD3D and Lac3D measurements. HGG exhibited significantly higher fractality and lower lacunarity in the enhancing subcomponent, along with lower fractality in the non‐enhancing subcomponent compared to LGG. This suggests that a highly irregular and complex geometry in the enhancing‐subcomponent is a characteristic feature of HGGs. A comparison of FD3D and Lac3D between IDH‐wild type and IDH‐mutant gliomas revealed that mutant gliomas had ~2.5‐fold lower FD3D in the enhancing‐subcomponent and higher FD3D with lower Lac3D in the non‐enhancing subcomponent, indicating a less complex and smooth enhancing subcomponent, and a more continuous non‐enhancing subcomponent as features of IDH‐mutant gliomas. Supervised ML models using FD3D from both the enhancing and non‐enhancing subcomponents together demonstrated high‐sensitivity in discriminating glioma grades (~97.9%) and IDH status (~94.4%). A combined fractal estimation of the enhancing and non‐enhancing subcomponents using MR images could serve as a non‐invasive, precise, and quantitative measure for discriminating glioma grade and IDH status. The combination of 2‐hydroxyglutarate‐magnetic resonance spectroscopy (2HG‐MRS) with FD3D and Lac3D quantification may be established as a robust imaging signature for glioma subtyping.