Impact of bariatric surgery on monthly earnings and employment: a national linked data study in England, 2014-2022

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Abstract Objective Evaluate the impact of bariatric surgery on monthly earnings and employee status among working-age adults, examine variations across sociodemographic characteristics. Design Retrospective longitudinal cohort study using national, linked administrative datasets. Setting Hospital inpatient services in England between 1 April 2014 31 December 2022. Participants 40,662 individuals who had a procedure obesity diagnosis during period, with no history previous 5 years, were 25 to 64 years old at date surgery. We also included 49,921 sampled from general population not matched by age sex those Main outcome measures Monthly pay – for all months only where individual was paid employment expressed 2023 prices; status. Results Among people living surgery, there sustained increase six after mean £84 per month compared before employment, probability being 4 4.3 percentage points The increases greater males. over 5-year follow up time youngest groups. Conclusions Bariatric is associated an increased employed, resulting earnings. These findings suggest that negatively impacts labour market outcomes management interventions are likely generate economic benefits both macroeconomic level increasing likelihood obesity.

Language: Английский

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A CNN Autoencoder for Learning Latent Disc Geometry from Segmented Lumbar Spine MRI

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Purpose Low back pain is the world’s leading cause of disability and pathology lumbar intervertebral discs frequently considered a driver pain. The geometric characteristics offer valuable insights into their mechanical behavior pathological conditions. In this study, we present convolutional neural network (CNN) autoencoder to extract latent features from segmented disc MRI. Additionally, interpret these demonstrate utility in identifying pathology, providing complementary perspective standard measures. Methods We examined 195 sagittal T1-weighted MRI spine publicly available multi-institutional dataset. proposed pipeline includes five main steps: 1) segmenting MRI, 2) training CNN extracting features, 3) measuring 4) predicting narrowing with and/or 5) determining relationship between features. Results Our segmentation model achieved an IoU 0.82 (95% CI: 0.80–0.84) DSC 0.90 0.89–0.91). minimum bottleneck size for which converged was 4×1 after 350 epochs (IoU 0.9984 - 95% 0.9979–0.9989). Combining improved predictions compared using either feature set alone. Latent encoded shape angular orientation. Conclusions This study presents CNN-autoencoder enhancing prediction interpretability. Future work will integrate voxel intensity analyze composition.

Language: Английский

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Modeling glioma-induced impairments on the glymphatic system

Published: April 21, 2025

Abstract Altered glymphatic function is observed for many neurological diseases. Glioma, one of the most common brain cancers, known to have altered fluid dynamics in terms edema and blood-brain-barrier breakdown, both features potentially impacting function. To study glioma its dynamics, we propose a flexible mathematical model, including tumor, peri-tumoral as well healthy tissue. From mechanical point view, consider multicompartment porous medium model movement clearance solutes that are convected but also diffuse extra-cellular space. Our results indicate impairment on system due growth two-fold. First, resulting from leakage blood vessels or occlusion peri-vascular spaces, considered an exit route, result local high pressure zone, consequently impairing negatively clearance. Second, changes porosities (volume fraction certain compartments such perivascular extracellular spaces), disruption transport brain. effect similar enhanced permeability retention obtained using biologically relevant parameter values our model. can be viewed first step towards digital twin drug contrast product delivery within cerebro-spinal directly ( e . g intrathecal injection) patients suffering gliomas.

Language: Английский

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An Aggressive Interaction Rapidly Increases Brain Androgens in a Male Songbird during the Non-breeding Season

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(23), P. e1095232024 - e1095232024

Published: April 24, 2024

Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression during breeding season. However, can be expressed non-breeding season, despite low androgen synthesis gonads. The brain also synthesize steroids (neurosteroids), including androgens, which might Male song sparrows, Melospiza melodia , are territorial year-round and allow study of seasonal changes steroid modulation aggression. Here, we quantified following simulated intrusion (STI) for 10 min wild adult male sparrows seasons. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), examined 11 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5a-dihydrotestosterone, 17-estradiol, 17a-estradiol, estriol, estrone. Steroids were measured blood microdissected regions regulate social behavior. In both seasons, STI increased corticosterone brain. had no rapid effects on androgens or estrogens. Intriguingly, testosterone androstenedione several behaviorally relevant regions, but not blood, where remained non-detectable. Also progesterone specific regions. Overall, socially modulated levels more prominent Brain vary with season context region-specific manner suggest role neuroandrogens

Language: Английский

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AlphaFold2 can predict single-mutation effects

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 14, 2022

AlphaFold2 (AF) is a promising tool, but it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1-3 mutations – as measured effective strain correlated across 3,901 experimental and AF-predicted structures. Furthermore, analysis of ∼11,000 proteins shows local change correlates with various phenotypic changes. These findings suggest AF can range magnitude single-mutation effects on average, propose method improve precision predictions indicate when are unreliable.

Language: Английский

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AI-predicted protein deformation encodes energy landscape perturbation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 12, 2023

AI algorithms have proven to be excellent predictors of protein structure, but whether and how much these can capture the underlying physics remains an open question. Here, we aim test this question using Alphafold2 (AF) algorithm: We use AF predict subtle structural deformation induced by single mutations, quantified strain, compare with experimental datasets corresponding perturbations in folding free energy ΔΔ G . Unexpectedly, find that physical strain alone – without any additional data or computation correlates almost as well state-of-the-art energy-based machine-learning predictors. This indicates AF-predicted structures encode fine details about landscape. In particular, significant information on stability, enough estimate (de-)stabilizing effects thus paving way for development novel, structure-based stability design evolution.

Language: Английский

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The widely used cymoxanil fungicide impairs respiration inSaccharomyces cerevisiaevia cytochromecoxidase inhibition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 3, 2024

Abstract Cymoxanil (CYM) is a synthetic acetamide fungicide that has been widely used to combat downy mildew diseases in grapevine cultures and late blight tomato potato caused by the oomycetes Plasmopara viticola Phytophthora infestans , respectively. Despite its extensive application, biochemical mode of action CYM remains elusive. Previous reports indicate affects growth, DNA RNA synthesis inhibits cell biomass production respiration rate well-characterized fungal model Saccharomyces cerevisiae . We therefore this further characterize effect on mitochondria. found oxygen consumption whole cells after 3 h exposure, which persists over time. Using isolated mitochondria, we demonstrated specifically cytochrome c oxidase (C O) activity during oxidative phosphorylation. Based molecular docking algorithms, propose acts blocking interaction (cyt ) with C O, hampering electron transfer inhibiting O catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into can instrumental drive informed management use fungicide.

Language: Английский

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Predictive Control of Musculotendon Loads Across Fast and Slow-twitch Muscles in a Simulated System with Parallel Actuation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 15, 2024

Abstract Research in lower limb wearable robotic control have largely focused on reducing the metabolic cost of walking or compensating for a portion biological joint torque e.g., by applying support proportional to estimated torques. However, due different musculotendon unit (MTU) contractile speed properties, less attention has been given development controllers that can steer MTU dynamics directly. Therefore, closed-loop needs be robust across fiber phenotypes, i.e. ranging from slow type I fast IIx humans. The ability in-vivo MTUs, could lead new class robots provide precise targeted preventing onset injury precision rehabilitation selected damaged tissues. In this paper, we introduce novel framework utilizes Nonlinear Model Predictive Control (NMPC) keep peak Achilles tendon force within predetermined boundaries during diverse range cyclic production simulations human ankle plantarflexors. This employs computationally efficient model comprising modified Hill-type contraction component and with parallel actuation. Results indicate closed-form muscle-actuation model’s computational time is order microseconds muscle velocity properties. Furthermore, controller achieves timeframe below 14 ms , aligning physiological electromechanical delay facilitating its potential future real-world applications.

Language: Английский

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Regulation of sex differences in innate immunity by sex-determining gene transformer in Drosophila melanogaster

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Abs tra ct Sex dimorphism is one of the key features dioecious organisms, which shapes almost all aspects life history traits from early development to cessation life. However, specific regulatory differences between males and females that underlie sex are underexplored for most quantitative traits, including immune dimorphism. Complex patterns variation, example, with respect numbers types contributing alleles, dynamic changes in gene expression, context dependency, have created challenges understanding mechanistic basis immunity. To investigate immunity, we focused on determination hierarchy master switch, transformer ( ), Drosophila melanogaste r. Two different perturbations were examined, pseudomales tra- mutant) pseudofemales overexpression). Changes expression response infection Providencia rettgeri , an ex cellular gram-negative bacterium, examined each these controls wild-type phenotypes. best our knowledge, this first study report bacterial any insects mutant or overexpressed genotypes. Survival load characterized assess overall impact examine role gene, differentially regulated genes identified comparisons wound control infected flies males, females, overexpression animals. The survival assay showed absence female-specific isoform (Tra F XX animals significantly lower than their rate aligned males. Tra XY resulted a surprising outcome, much higher relative both females. DEG analysis significant interaction status 235 417 upstream downstream pathway, respectively. Interestingly, GO enrichment found 49 response-related biological processes enriched among Toll signaling no categories . Further regulators pathway its targets signal detection, transduction, response, pathway. Moreover, several can regulate IMD pathways via transcription factor NF-kB-Relish some regulators, such as Diap2/IAP2 Charon. Overall, findings highlighted strong potential establish Drosophila.

Language: Английский

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Designing symmetrical multi-component proteins using a hybrid generative AI approach

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 15, 2024

Abstract Proteins, the fundamental building blocks of biological function, orchestrate complex cellular processes by assembling into intricate structures through meticulous interactions. The design specific protein-protein interfaces to create customized protein assemblies holds immense potential for various biotechnological applications. To address current limitations in designing heteromeric interactions multi-component assemblies, we developed a hybrid generative AI approach. This method combines deep learning and automated reasoning, explicitly considering both positive negative interaction states favor desired over undesired approach leverages Effie, deep-learned pairwise decomposable scoring an advanced reasoning tool extended multicriteria optimization this function. Here, tested ability redesign homomeric bacterial microcompartment components (BMC-H) assemblies. We benchmarked its performance against ProteinMPNN, sequence autoregressive model. Our silico assessment, complemented experimental validation, highlights outperformance approach, unlock engineering self-assembling entities.

Language: Английский

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