julilili42/papers huggingface dataset:
28 Utilization of pharmacogenetic medications at a German pediatric University Hospital
2024-07-31

<h3>Introduction</h3> Pharmacogenetic (PGx) guided drug therapy is a promising approach for improving drug response and safety. The implementation of PGx information into clinical routine is currently ongoing in adult medicine, but still limited in pediatrics. Thus, we aimed to analyze the impact of PGx on the prescription of medications used in the real-world setting of a German Children's University hospital. <h3>Methodology</h3> A retrospective database analysis was performed using routine medication data from patients on general pediatric wards between 2014 and 2019. The database included 25,339 admissions of 16,289 patients. Of these, we analyzed the 17,543 admissions of 11,611 patients who received medication during hospital stays (i) to elucidate the frequency of PGx relevant drugs and (ii) to identify underlying PGx target genes. For the analyses we considered all currently listed 74 drugs with a pediatric guideline annotation on PharmGKB.org website. An age-stratified ranking list for clinically relevant PGx medications has been established. <h3>Results</h3> 37.9% (n = 4,401) of all hospitalized patients with medication (n = 11,611) received at least one PGx drug. Only 35 of the 74 PGx drugs with pediatric recommendations were used, resulting in 5,633 exposures to PGx drugs. The most commonly administered PGx drugs were ibuprofen (3,407/5,633, 60.5%), omeprazole (797/5,633, 14.1%), tobramycin (409/5,633, 7.3%), tramadol (198/5,633, 3.5%) and ondansetron (174/5,633, 3.1%). There were no age dependent differences regarding drug exposure except for aminoglycosides which were more often used in neonates, infants and toddlers. The analysis of PGx recommendations related to pharmacogenes resulted in 17 genes relevant for our study population. Here, CYP2C9, CYP2C19, CYP2D6, MT-RNR1, and HLA-B*15:02 are the top candidates. <h3>Conclusion</h3> Similar to adults, a high proportion of children and adolescents are treated with at least one PGx drug at our pediatric center, for which PGx guidelines recommend genetic testing preemptively. Based on our prescription data a total of 17 PGx genes should be considered for testing in clinical routine. In addition to PGx, developmental aspects of pharmacotargets need to be addressed in more detail to refine the implementation of PGx into pediatric medicine.
Review of Particle Physics
2024-08-01

The summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,717 new measurements from 869 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Most of the 120 reviews are updated, including many that are heavily revised. The is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings. The complete (both volumes) is published online on the website of the Particle Data Group () and in a journal. Volume 1 is available in print as the . A with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app. The 2024 edition of the Review of Particle Physics should be cited as: S. Navas et al. (Particle Data Group), Phys. Rev. D 110, 030001 (2024) © 2024 2024
Quasinormal modes and their excitation beyond general relativity
2024-08-01

The response of black holes to small perturbations is known to be partially described by a superposition of quasinormal modes. Despite their importance to enable strong-field tests of gravity, little to nothing is known about what overtones and quasinormal-mode amplitudes are like for black holes in extensions to general relativity. We take a first step in this direction and study what is arguably the simplest model that allows first-principle calculations to be made: a nonrotating black hole in an effective-field-theory extension of general relativity with cubic-in-curvature terms. Using a phase-amplitude scheme that uses analytical continuation and the Prüfer transformation, we numerically compute, for the first time, the quasinormal overtone frequencies (in this theory) and quasinormal-mode excitation factors (in any theory beyond general relativity). We find that the overtone quasinormal frequencies and their excitation factors are more sensitive than the fundamental mode to the length scale l introduced by the higher-derivative terms in the effective field theory. We argue that a description of all overtones cannot be made within the regime of validity of the effective field theory, and we conjecture that this is a general feature of any extension to general relativity that introduces a new length scale. We also find that a parametrization of the modifications to the general-relativistic quasinormal frequencies in terms of the ratio between l and the black hole's mass is somewhat inadequate, and we propose a better alternative. As an application, we perform a preliminary study of the implications of the breakdown, in the effective field theory, of the equivalence between the quasinormal mode spectra associated to metric perturbations of polar and axial parity of the Schwarzschild black hole in general relativity. We also present a simple justification for the loss of isospectrality.
Advancing Parsimonious Deep Learning Weather Prediction Using the HEALPix Mesh
2024-08-01

Abstract We present a parsimonious deep learning weather prediction model to forecast seven atmospheric variables with 3‐hr time resolution for up to 1‐year lead times on a 110‐km global mesh using the Hierarchical Equal Area isoLatitude Pixelization (HEALPix). In comparison to state‐of‐the‐art (SOTA) machine learning (ML) weather forecast models, such as Pangu‐Weather and GraphCast, our DLWP‐HPX model uses coarser resolution and far fewer prognostic variables. Yet, at 1‐week lead times, its skill is only about 1 day behind both SOTA ML forecast models and the SOTA numerical weather prediction model from the European Center for Medium‐Range Weather Forecasts. We report several improvements in model design, including switching from the cubed sphere to the HEALPix mesh, inverting the channel depth of the U‐Net, and introducing gated recurrent units (GRU) on each level of the U‐Net hierarchy. The consistent east‐west orientation of all cells on the HEALPix mesh facilitates the development of location‐invariant convolution kernels that successfully propagate weather patterns across the globe without requiring separate kernels for the polar and equatorial faces of the cube sphere. Without any loss of spectral power after the first 2 days, the model can be unrolled autoregressively for hundreds of steps into the future to generate realistic states of the atmosphere that respect seasonal trends, as showcased in 1‐year simulations.
HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES
2024-08-01

HSD3B1 encodes 3β-hydroxysteroid dehydrogenase-1, which converts adrenal dehydroepiandrosterone to 5α-dihydrotestosterone and is inherited in adrenal-permissive (AP) or adrenal-restrictive forms. The AP allele is linked to castration resistance, mainly in low-volume tumors. Here, we investigate the association of HSD3B1 alleles with outcomes in ARCHES, a multinational, double-blind, randomized, placebo-controlled phase 3 trial that demonstrated clinical benefit with enzalutamide plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) compared to those treated with placebo plus ADT. There are no significant differences between genotypes for clinical efficacy endpoints. Enzalutamide significantly improves radiographic progression-free survival and overall survival vs. placebo irrespective of HSD3B1 status. Men with the AP genotype have higher post-progression mortality and treatment-emergent adverse events, including hypertension, cardiovascular events, and gynecomastia, but a lower fracture rate. Overall, enzalutamide is beneficial in men with mHSPC independent of the HSD3B1 genotype. Inherited polymorphisms of HSD3B1 may account for differential toxicities.
Bacteroides uniformis Ameliorates Carbohydrate and Lipid Metabolism Disorders in Diabetic Mice by Regulating Bile Acid Metabolism via the Gut–Liver Axis
2024-08-01

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.
The giant outburst of EXO 2030+375
2024-08-01

The Be X-ray binary EXO 2030+375 went through its third recorded giant outburst from June 2021 to early 2022. We present the results of both spectral and timing analysis based on NICER monitoring, covering the 2−10 keV flux range from 20 to 310 mCrab. Dense monitoring with observations carried out about every second day and a total exposure time of ∼160 ks allowed us to closely track the source evolution over the outburst. Changes in the spectral shape and pulse profiles showed a stable luminosity dependence during the rise and decline. The same type of dependence has been seen in past outbursts. The pulse profile is characterized by several distinct peaks and dips. The profiles show a clear dependence on luminosity with a stark transition at a luminosity of ∼2 × 10 36 erg s −1 , indicating a change in the emission pattern. Using relativistic raytracing, we demonstrate how anisotropic beaming of emission from an accretion channel with a constant geometrical configuration can give rise to the observed pulse profiles over a range of luminosities.
Was the steppe bison a grazing beast in Pleistocene landscapes?
2024-08-01

The history and palaeoecology of the steppe bison ( Bison priscus ) remain incompletely understood despite its widespread distribution. Using dental microwear textural analysis (DMTA) and vegetation modelling, we reconstructed the diet and assessed the habitat of steppe bison inhabiting Eurasia and Alaska since the Middle Pleistocene. During the Late Pleistocene, steppe bison occupied a variety of biome types: from the mosaic of temperate summergreen forest and steppe/temperate grassland (Serbia) to the tundra biomes (Siberia and Alaska). Despite the differences in the identified biome types, the diet of steppe bison did not differ significantly among populations in Eurasia. DMTA classified it as a mixed forager in all populations studied. The DMTA of Bb1 bison—a recently identified genetically extinct sister-clade of Bison bonasus —was typical of a highly grazing bovid species and differed from all B. priscus populations. The results of the study temper the common perception that steppe bison were grazers in steppe habitats. The dietary plasticity of the steppe bison was lower when compared with modern European bison and may have played an important role in its extinction, even in the stable tundra biome of eastern Siberia, where it has survived the longest in all of Eurasia.
A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma
2024-08-01

Here, we present a method for enrichment of double-stranded cfDNA with an average length of ∼40 bp from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we find significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA methylation, positively with H3K4me3 histone modifications and gene transcription. The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not yet been recognized. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with postoperative controls, we identify 136 and 241 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis, demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.
In Vivo Molecular Imaging of Breast Cancer Metabolic Heterogeneity Using [1-13C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen
2024-08-01

Metabolic MRI using hyperpolarized (HP) [1-13C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at μT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate. In this study, we used SLIC-SABRE to conduct in vivo tumor metabolic imaging in a transgenic breast cancer mouse model (MMTV-PyMT). In agreement with previous HP MRI cancer studies, an elevated lactate metabolism was found in tumors compared to healthy breast tissue, heart, and vasculature, as well as distinct metabolic profiles within different tumor compartments. These findings suggest a potential link between lactate-to-pyruvate ratios and the varying levels of tumor cell proliferation and apoptosis observed by histological analyses. Our results underscore the potential of SABRE to enhance the accessibility and throughput of HP MRI, thereby advancing cancer research and diagnostic oncology.
A Reproducible Tutorial on Reproducibility in Database Systems Research
2024-08-01

Reproducibility is a key aspect of the scientific method, and it is essential for building trust in the results of research. This tutorial aims to provide concrete guidance on how to leverage containerized reproducibility using Docker for database systems research. In this tutorial, we present a step-by-step guide on how to prepare a Docker-based artifact for an experiment. We will cover topics such as Dockerfiles, Docker images, Docker Compose, automation using Python, Bash, and Make, and also artifact documentation and packaging best practices. The tutorial itself is a reproducible artifact, and we provide a public GitHub repository with all the code and examples used in the tutorial. This repository can serve as a starting point to prepare artifacts for experiments and publications.
Do we need another screw? Sacroiliac screw fixation in open-book pelvic ring injuries (APC type II)
2024-08-01

Purpose To compare anterior plate fixation (SP fixation) both alone and in combination with an additional posterior sacroiliac screw (SP+SIS fixation) as a treatment for pelvic ring injuries with widening of the pubic symphysis and disruption to the anterior sacroiliac ligaments. Methods To find studies with pelvic ring injuries (APC II; B2.3d) and SP or SP+SIS fixation, a systematic literature review was conducted by searching four databases. A protocol was published a priori at Open Science Framework ( https://doi.org/10.17605/OSF.IO/3YHAV ). Exclusion criteria included perineal injuries, chronic instability of the symphysis, complete sacroiliac separation, and pediatric patients (age &lt;18 years). Primary outcomes of interest were defined as implant failure, health-related quality of life, and revision rate. Results Altogether, 1861 studies were screened, and 40 studies qualified for full-text analysis. In total, 14 studies (two surveys, six biomechanical studies, and six retrospective clinical studies) were included. The surveys revealed that surgeons who had more recently begun practicing were more likely to use posterior fixation (SP+ISS). The biomechanical studies were heterogenous and did not yield a uniform pattern. In clinical studies, 117 patients (45%) received SP fixation, and 142 patients (55%) received SP+SIS fixation. Complications occurred in 31 SP patients (30%) and in five SP+SIS patients (3.5%). Conclusion A high risk of bias was uncovered, and reporting was found to be incomplete. SP+SIS may have the potential to improve outcomes, but the evidence remains too inconclusive to draw reliable recommendations.
The MuscleSCS Technique (4-8Hz BurstDRTM Octrode™): A Randomized Clinical Study of MuscleSCS Stimulation in the Treatment of Chronic Back Pain
2024-08-01

BACKGROUND: MuscleSCS is a new technique that combines spinal cord stimulation (SCS) with muscle stimulation to relieve pain. OBJECTIVES: In this clinical study, we wanted to use rod electrodes to investigate the MuscleSCS method’s effectiveness in the treatment of chronic lower back pain. One of our hypotheses was that the combined use of MuscleSCS and BurstDRTM would further improve the treatment. STUDY DESIGN: A prospective, single-center, single-blinded, randomized crossover study. SETTING: A university medical center. METHODS: Patients with chronic lower back pain had previously (one to 10 years ago) received an SCS system (OctrodeTM). In this study, they were randomly treated for 2 weeks each with BurstDRTM stimulation alone, MuscleSCS stimulation alone, or a combination of BurstDRTM stimulation and MuscleSCS stimulation. Thereafter, the patients were treated for another 6 weeks with one of the 3 methods (crossover possible). Pain ratings on the visual analog scale (VAS) were recorded and compared. A Pain Disability Index (PDI) questionnaire was used at the baseline and at 3 months. RESULTS: We included 24 patients in this study (11 women, mean age 62.3 yrs.) The values of the second week of the stimulation were the only ones used for the calculations. The first week of the stimulation was used as a wash-out period. The combined application of BurstDRTM and MuscleSCS stimulation was associated with the best results (P = 0.032). PDI scores did not improve during this treatment. No serious adverse events occurred during this study. Seventy-one and a half percent of the patients experienced an improvement in their pain as a result of the additional MuscleSCS stimulation. LIMITATIONS: In this study, only one fixed contact setting (3 &amp; 4) was used to ensure uniform conditions for all patients and the ability to compare the different treatment modes. CONCLUSION: This study showed that the combined application of SCS (BurstDRTM) and additional MuscleSCS stimulation using a rod electrode could significantly improve outcomes for patients suffering from chronic back pain. KEY WORDS: Spinal cord stimulation, muscle stimulation, chronic back pain, low-frequency stimulation, MuscleSCS
Averaging Times for Pulse Oximeter Measurements – A Review of Manuscripts Published in the Top Five Sleep Medicine Journals
2024-08-01

The AVT is only rarely mentioned in sleep medicine papers, despite its influence on sleep study results. Reported AVTs were heterogenous. Further research is warranted to set up guidelines for using or reporting the AVT.
The challenges and opportunities of researching masculinities during peace processes
2024-08-01

This article introduces a special issue in Peacebuilding on researching masculinities during peace processes. It collates insights from feminist peace research, and research on gender and masculinities, to highlight how peace processes are necessarily also processes of gender re-negotiation and transformation. We argue that researching masculinities entails accounting for their plural circulation, complex and contradictory dynamics, and multiple effects. Researching masculinities additionally generates methodological dilemmas that require researchers' reflexive engagement. The articles in the special issue address critical themes and topics pertaining to masculinities and peace across a wide range of participant experience in diverse contexts (including Bosnia, Indonesia, Liberia, Timor-Leste, Uganda, and the UK). We summarise authors' critical and empirical contributions and chart their methodological innovations and strategies. We see plural masculine performances and identities not as obstacles to be overcome in/through research but as opportunities to generate discussion with research participants about the operability and impacts of gender.