Miracle-dz/UniFAR-FTUs huggingface dataset:
Daytime dysfunction may be associated with postoperative delirium in patients undergoing total hip/knee replacement: The PNDABLE study

Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self‐reported sleep characteristics and POD in patients has been investigated in this study.
Daily Mean Sea Level Pressure Reconstructions for the European–North Atlantic Region for the Period 1850–2003

Abstract The development of a daily historical European–North Atlantic mean sea level pressure dataset (EMSLP) for 1850–2003 on a 5° latitude by longitude grid is described. This product was produced using 86 continental and island stations distributed over the region 25°–70°N, 70°W–50°E blended with marine data from the International Comprehensive Ocean–Atmosphere Data Set (ICOADS). The EMSLP fields for 1850–80 are based purely on the land station data and ship observations. From 1881, the blended land and marine fields are combined with already available daily Northern Hemisphere fields. Complete coverage is obtained by employing reduced space optimal interpolation. Squared correlations (r 2) indicate that EMSLP generally captures 80%–90% of daily variability represented in an existing historical mean sea level pressure product and over 90% in modern 40-yr European Centre for Medium-Range Weather Forecasts Re-Analyses (ERA-40) over most of the region. A lack of sufficient observations over Greenland and.
Applied physiologically‐based pharmacokinetic modeling to assess uridine diphosphate‐glucuronosyltransferase‐mediated drug–drug interactions for Vericiguat

Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate‐glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug–drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically‐based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration‐time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7‐fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non‐wild‐type variants for both isoforms. This study is a first cornerstone to qualify the PK‐Sim platform for use of UGT‐mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.
Prospective comparison of diagnostic tests for bile acid diarrhoea

Bile acid diarrhoea is often missed because gold standard nuclear medicine tauroselcholic [75‐Se] acid (SeHCAT) testing has limited availability. Empirical treatment effect has unknown diagnostic performance, whereas plasma 7α‐hydroxy‐4‐cholesten‐3‐one (C4) is inexpensive but lacks sensitivity.
Stable carbon isotope ratios in atmospheric methane and some of its sources

Ratios of 13C/12C have been measured in atmospheric methane and in methane collected from sites and biota that represent potentially large sources of atmospheric methane. These include temperate marshes (∼−48‰ to ∼−54‰), landfills (∼−51‰ to ∼−55‰), and the first reported values for any species of termite (−72.8 ± 3.1‰ for Reticulitermes tibialis and −57.3 ± 1.6‰ for Zootermopsis angusticollis). Numbers in parentheses are δ13C values with respect to PDB (Peedee belemnite) carbonate. Most methane sources reported thus far are depleted in 13C with respect to atmospheric methane (−47.0 ± 0.3‰). Individual sources of methane should have 13C/12C ratios characteristic of mechanisms of CH4 formation and consumption prior to release to the atmosphere. The mass-weighted average isotopic composition of all sources should equal the mean 13C of atmospheric methane, corrected for a kinetic isotope effect in the OH attack of CH4. Assuming the kinetic isotope effect to be small (∼−3.0‰ correction to −47.0), as in the literature, the new values given here for termite methane do not help to explain the apparent discrepancy between 13C/12C ratios of the known CH4 sources and that of atmospheric CH4.
The Drosophila melanogaster prophenoloxidase system participates in immunity against Zika virus infection

Drosophila melanogaster relies on an evolutionarily conserved innate immune system to protect itself from a wide range of pathogens, making it a convenient genetic model to study various human pathogenic viruses and host antiviral immunity. Here we explore for the first time the contribution of the Drosophila phenoloxidase (PO) system to host survival and defenses against Zika virus (ZIKV) infection by analyzing the role of mutations in the three prophenoloxidase (PPO) genes in female and male flies. We show that only PPO1 and PPO2 genes contribute to host survival and appear to be upregulated following ZIKV infection in Drosophila. Also, we present data suggesting that a complex regulatory system exists between Drosophila PPOs, potentially allowing for a sex‐dependent compensation of PPOs by one another or other immune responses such as the Toll, Imd, and JAK/STAT pathways. Furthermore, we show that PPO1 and PPO2 are essential for melanization in the hemolymph and the wound site in flies upon ZIKV infection. Our results reveal an important role played by the melanization pathway in response to ZIKV infection, hence highlighting the importance of this pathway in insect host defense against viral pathogens and potential vector control strategies to alleviate ZIKV outbreaks.
Deep learning tools to accelerate antibiotic discovery

ABSTRACT Introduction As machine learning (ML) and artificial intelligence (AI) expand to many segments of our society, they are increasingly being used for drug discovery. Recent deep learning models offer an efficient way to explore high-dimensional data and design compounds with desired properties, including those with antibacterial activity. Areas covered This review covers key frameworks in antibiotic discovery, highlighting physicochemical features and addressing dataset limitations. The deep learning approaches here described include discriminative models such as convolutional neural networks, recurrent neural networks, graph neural networks, and generative models like neural language models, variational autoencoders, generative adversarial networks, normalizing flow, and diffusion models. As the integration of these approaches in drug discovery continues to evolve, this review aims to provide insights into promising prospects and challenges that lie ahead in harnessing such technologies for the development of antibiotics. Expert opinion Accurate antimicrobial prediction using deep learning faces challenges such as imbalanced data, limited datasets, experimental validation, target strains, and structure. The integration of deep generative models with bioinformatics, molecular dynamics, and data augmentation holds the potential to overcome these challenges, enhance model performance, and utlimately accelerate antimicrobial discovery.
Harvesting Intensity at Clear-Felling in the Boreal Forest

The amount of logging residues left on site after clear-felling has been shown to influence the state of soil nutrient resources, but this effect may depend on soil conditions. In three regions of the boreal zone of Quebec, with contrasting soil characteristics, soil and foliar nutrient status of young (15-20 yr old) stands were compared among sites that were clear-felled at two harvesting intensities, that is, stem-only (SOH) and whole-tree harvesting (WTH). Balsam fir (Abies balsamea) stands were studied in the Foret Montmorency and Gaspesie regions, while black spruce [Picea mariana (Mill.) B.S.P.] and jack pine (Pinus banksiana Lamb.) were studied in the Haute-Mauricie region. Whole-tree harvesting resulted in lower cation exchange capacity (CEC) compared with SOH, but this effect could be linked to decreased levels of organic C only in the Haute-Mauricie region, where soils had intrinsically low organic matter content. Lower soil and foliar Ca concentrations after WTH were observed in all three regions. Foliar Ca status was most strongly affected by harvesting intensity in Gaspesie, where soils exhibited the lowest concentration of total Ca in the parent material. In Haute-Mauricie, where the parent material contained a low level of Mg, foliar nutrition for this element was significantly poorer under WTH compared with SOH. Harvesting intensity did not influence the biogeochemical cycles of K and N. Foliar analysis revealed that jack pine exhibits the strongest nutritional difference between WTH and SOH. Results suggested that the tree species regenerating the harvested sites, as well as the total Ca and Mg contents of the parent material are better indicators of a site's susceptibility to nutritional alteration by WTH than soil available nutrient status.
Psychosocial interventions for survivors of rape and sexual assault experienced during adulthood (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of psychosocial interventions on mental health and well­being for survivors of rape and sexual assault experienced during adulthood. Psychosocial interventions for survivors of rape and sexual assault experienced during adulthood (Protocol) Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
Colocalization of TDP‐43 and stress granules at the early stage of TDP‐43 aggregation in amyotrophic lateral sclerosis

Abstract TDP‐43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP‐43 in ALS, corresponding to nonfibrillar TDP‐43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP‐43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP‐43 inclusions. Formalin‐fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2–5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR‐positive. In short‐duration and standard‐duration ALS, the number of HuR‐positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short‐duration ALS than in standard‐duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome‐like granular structures in DPCS areas and RIs were labeled with anti‐HuR, whereas skeins were not. These findings suggest that colocalization of TDP‐43 and SGs occurs at the early stage of TDP‐43 aggregation.
Effects of adding exercise to usual care on blood pressure in patients with hypertension, type 2 diabetes, or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis

Introduction: Exercise is the most recommended lifestyle intervention in managing hypertension, type 2 diabetes, and/or cardiovascular disease; however, evidence in lowering blood pressure is still inconsistent and often underpowered. Method: We conducted a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials adding any form of trialist defined exercise to usual care versus usual care and its effect on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in participants with hypertension, type 2 diabetes, or cardiovascular disease searched in different databases from inception to July 2020. Our methodology was based on PRISMA and Cochrane Risk of Bias-version1. Five independent reviewers extracted data and assessed risk of bias in pairs. Results: Two hundred sixty-nine trials randomizing 15 023 participants reported our predefined outcomes. The majority of exercise reported in the review was dynamic aerobic exercise (61%), dynamic resistance (11%), and combined aerobic and resistance exercise (15%). The trials included participants with hypertension (33%), type 2 diabetes (28%), or cardiovascular disease (37%). Meta-analyses and trial sequential analyses reported that adding exercise to usual care reduced SBP [mean difference (MD) MD: −4.1 mmHg; 95% confidence interval (95% CI) −4.99 to −3.14; P < 0.01; I2 = 95.3%] and DBP (MD: −2.6 mmHg; 95% CI −3.22 to −2.07, P < 0.01; I2 = 94%). Test of interaction showed that the reduction of SBP and DBP was almost two times higher among trials from low-and middle-income countries (LMICs) as compared to high-income countries (HICs). The exercise induced SBP reduction was also higher among participants with hypertension and type 2 diabetes compared to participants with cardiovascular disease. The very low certainty of evidence warrants a cautious interpretation of the present results. Conclusion: Adding any type of exercise to usual care may be a potential complementary strategy for optimal management of blood pressure for patients with hypertension, type 2 diabetes, or cardiovascular disease, especially, in LMICs. PROSPERO registration number CRD42019142313
Molecular characterization of cancer-intrinsic immune evasion genes indicates prognosis and tumour microenvironment infiltration in osteosarcoma

Cancer-intrinsic immune evasion (IE) to cells is a critical factor in tumour growth and progression, yet the molecular characterization of IE genes (IEGs) in osteosarcoma remains underexplored. In this study, 85 osteosarcoma patients were comprehensively analyzed based on 182 IEGs, leading to the identification of two IE clusters linked to distinct biological processes and clinical outcomes. In addition, two IE clusters demonstrated diverse immune cell infiltration patterns, with IEGcluster A displaying increased levels compared to IEGcluster B. Moreover, an IE score was identified as an independent prognostic factor and nomogram may serve as a practical tool for the individual prognostic evaluation of patients with osteosarcoma. Finally, GBP1, a potential biomarker with high expression in osteosarcoma was identified. The findings of this study highlight the presence of two IE clusters, each associated with differing patient outcomes and immune infiltration properties. The IE score may serve to assess individual patient IE characteristics, enhance comprehension of immune features, and guide more efficacious treatment approaches.
Managing pediatric Crohn’s disease: recent insights

ABSTRACT Introduction Children and adolescents with Crohn’s disease present unique challenges due to extensive disease at diagnosis and the effect of bowel inflammation on growth. Historical approaches with corticosteroids and immunomodulators are far less effective than early treatment with anti-TNF biologics. Areas covered This review covers recent literature delineating the crucial role of early anti-TNF therapy in the treatment of moderate- to- severe Crohn’s disease in children and adolescents. The potential risks and benefits of concomitant immunomodulators are discussed, along with therapeutic anti-TNF drug monitoring, and reassessment by endoscopy and cross-sectional imaging to evaluate success beyond symptom control. Expert opinion Standard of care therapy for moderate-to-severe pediatric Crohn’s disease now entails precision dosing of anti-TNF therapy with periodic reassessment of bowel inflammation. The role of dietary modification continues to evolve. Current and future efforts need to be directed to elucidating ways to predict response to anti-TNF therapy and quickly changing to agents with other mechanisms of action when needed. Inordinate regulatory delays in approval of new therapies approved for adults continue to handicap pediatric clinicians and frequently limits their treatment choices, or forces them to give medications “off label. ” Only a concerted effort by clinicians, pharma, and regulators will improve this situation.
FreqSense: Adaptive Sampling Rates for Sensor-Based Human Activity Recognition Under Tunable Computational Budgets

Recent years have witnessed great success of deep convolutional networks in sensor-based human activity recognition (HAR), yet their practical deployment remains a challenge due to the varying computational budgets required to obtain a reliable prediction. This article focuses on adaptive inference from a novel perspective of signal frequency, which is motivated by an intuition that low-frequency features are enough for recognizing “easy” activity samples, while only “hard” activity samples need temporally detailed information. We propose an adaptive resolution network by combining a simple subsampling strategy with conditional early-exit. Specifically, it is comprised of multiple subnetworks with different resolutions, where “easy” activity samples are first classified by lightweight subnetwork using the lowest sampling rate, while the subsequent subnetworks in higher resolution would be sequentially applied once the former one fails to reach a confidence threshold. Such dynamical decision process could adaptively select a proper sampling rate for each activity sample conditioned on an input if the budget varies, which will be terminated until enough confidence is obtained, hence avoiding excessive computations. Comprehensive experiments on four diverse HAR benchmark datasets demonstrate the effectiveness of our method in terms of accuracy-cost tradeoff. We benchmark the average latency on a real hardware.
The autotaxin-LPA axis promotes membrane trafficking and secretion in yolk sac visceral endoderm cells

ABSTRACT Autotaxin, encoded by the Enpp2 gene, is an exoenzyme that produces lysophosphatidic acid, thereby regulating many biologic functions. We previously reported that Enpp2 mRNA was abundantly expressed in yolk sac visceral endoderm (VE) cells and that Enpp2−/− mice were lethal at embryonic day 9.5 owing to angiogenic defects in the yolk sac. Enpp2−/− mice showed lysosome fragmentation in VE cells and embryonic abnormalities including allantois malformation, neural tube defects, no axial turning, and head cavity formation. However, whether the defects in endocytic vesicle formation affect membrane trafficking in VE cells remained to be directly examined. In this study, we found that pinocytosis, transcytosis, and secretion of angiogenic factors such as vascular endothelial growth factor and transforming growth factor β1 were impaired in Enpp2−/− VE cells. Moreover, pharmacologic inhibition of membrane trafficking phenocopied the defects of Enpp2−/− mice. These findings demonstrate that Enpp2 promotes endocytosis and secretion of angiogenic factors in VE cells, thereby regulating angiogenesis/vasculogenesis and embryonic development.
Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial

ABSTRACT We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0–6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = −8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m’s fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8–14 m weight regain (aFMT = −0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8–14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance. ClinicalTrials.gov: NCT03020186
Current–voltage characteristics of focused ion beam fabricated superconducting tungsten meanders

We report on the superconducting properties and intermediate resistive steps (IRS) observed in the current–voltage characteristics (IVC) of tungsten meander (MW) structures fabricated using focused ion beam (FIB) technique. Three number of MWs were studied with individual wire widths of 240 nm, 640 nm and 850 nm with superconducting transition temperatures ( TC ) of 4.5 K, 4.55 K and 4.60 K respectively. The measured normal state resistance values at 8 K for these wires are of ∼182 kΩ, ∼49 kΩ and ∼32 kΩ, respectively as a function of increasing wire widths; are higher than the quantum of resistance ( h/4e2=6.45 kΩ, h is a Planck constant and e is electronic charge) indicating extreme disorder nature of the fabricated samples. The variation of resistance with respect to temperature (for T<TC ) follows the theoretical simulation of weak-link induced thermally activated phase slip (WL-TAPS) for the MW wire of width ∼240 nm, while for other samples the convergence between WL-TAPS and the experimental data are not so satisfactory. Though the IRS features are present in all the samples with varying degree of prominence, an external magnetic field causes its evolution demarcating different boundary lines with respect to temperatures. Herein, we believe that the occurrence of IRS is due to phase slip (PS) mechanism which further proliferates through phase slip centers or phase slip lines in IVC either with respect to temperature or magnetic field. As per our knowledge, such IRS features are not being reported for W-meander wires fabricated using FIB technique. The observation of PS (IRS) features is promising for the use of FIB fabricated W nanowires for various quantum applications including single photon detector, bolometers.