Functional Categories Research Articles

Prevalence and Clinical Implications of Osteosarcopenia in Patients with Acute Stroke: A Cross-sectional Study.

To investigate the prevalence and risk factors of osteosarcopenia in patients with acute stroke. Overall, 224 patients within 2 weeks of having a stroke were enrolled. Demographic characteristics, National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), modified Barthel Index (MBI), Functional Ambulation Category (FAC), Berg Balance Scale (BBS), and handgrip strength were recorded. Body composition was evaluated using dual-energy X-ray absorptiometry. Patients who met the diagnostic criteria for osteoporosis and sarcopenia were defined as having osteosarcopenia. The overall prevalence of osteoporosis and sarcopenia was 46.9% and 50.9%, respectively. The prevalence of osteoporosis without sarcopenia, sarcopenia without osteoporosis, and osteosarcopenia was 18.3%, 22.3%, and 28.6%, respectively. The proportion of female sex (71.9%), median age, and NIHSS score were significantly higher, and mRS, BBS, MBI, FAC, and grip strength were significantly lower in patients with osteosarcopenia. Older age (≥65-years) (OR, 15.4), female sex (OR, 6.23), and lower BMI (<25 kg/m 2 ) (OR, 43.13) were independently associated with the likelihood of osteosarcopenia. Osteosarcopenia may occur in acute stroke survivors. Patients with osteosarcopenia have a significantly higher stroke severity and disability. A comprehensive diagnostic approach is imperative for osteosarcopenia, thereby facilitating implementation of optimal rehabilitative strategies.

The Role of Workforce Diversity in Improving Organizational Sustainability and Innovation of the Manufacturing Industry in Nigeria

Objectives: The goal of this study was to see how worker diversity affected organisational sustainability and innovation in a specific manufacturing industry in Nigeria. Specifically the study determine the impact of gender, age diversity, ethnic diversity and educational diversity on the sustainability and innovation of organisations. Theoretical Framework: The management research, functional categories, social categories, and psychological research where explored in this study. These categories serve as illustrative examples within the broader context of understanding various dimensions of research in the field of management. Method: The study included a descriptive research design. Individual survey questionnaire were distributed to a sample of 20 companies and 81 participants from the indicated industrial industries. CVR=1 was obtained by using Lawshe's template to test the questionnaire's validity, while Cronbach Alpha was used and supplied a coefficient alpha of 0.86 to establish the questionnaire's homogeneity. Data was collected on-site and analysed using frequency counts and percentages. At p.01 and .05, the Spearman rank correlation coefficient was utilized to evaluate statistical significance. Findings: Gender, age, and educational background are all substantially connected with organizational sustainability and innovation, workforce diversity characteristics have been identified as major predictors of organizational sustainability and innovation, but ethnic diversity has been found to be negatively related to organisational sustainability and innovation. The implication is that the chosen manufacturing firm has an outstanding age, gender, and educational diversity composition, and that it must be handled properly to fully profit from the diversity. Conclusion: The selected manufacturing company must supply various skill maximization training to enhance the employees' current inventive capacity and ensure ethnic variable is handled the positive way to ensure organizational sustainability.

Longitudinal changes in vertical stride regularity, hip flexion, and knee flexion contribute to the alteration in gait speed during hospitalization for stroke

Changes in stride regularity and joint motion during gait appear to be related to improved gait speed in hospitalized patients with stroke. We aimed to clarify the changes in stride regularity and joint motion during gait through longitudinal observations. Furthermore, we aimed to clarify the relationship between changes in gait speed, stride regularity, and joint motion during gait. Seventeen inpatients with stroke were assessed for physical and gait functions at baseline, when they reached functional ambulation category 3, and before discharge. Physical function was assessed using the Fugl-Meyer assessment for the lower extremities and the Berg Balance Scale. Gait function was assessed on the basis of gait speed, joint motion, stride regularity, and step symmetry using inertial sensors. The correlations between the ratio of change in gait speed and each indicator from baseline to discharge were analyzed. Both physical and gait functions improved significantly during the hospital stay. The ratio of change in gait speed was significantly and positively correlated with the ratio of change in vertical stride regularity (r = 0.662), vertical step symmetry (rs = 0.627), hip flexion (rs = 0.652), knee flexion (affected side) (r = 0.611), and ankle plantarflexion (unaffected side) (rs = 0.547). Vertical stride regularity, hip flexion, and knee flexion (affected side) were significant factors in determining the ratio of changes in gait speed. Our results suggest that stride regularity, hip flexion, and knee flexion could explain the entire gait cycle and that of the affected side. These parameters can be used as indices to improve gait speed.

With a little help from my friends: the roles of microbial symbionts in insect populations and communities.

To understand insect abundance, distribution and dynamics, we need to understand the relevant drivers of their populations and communities. While microbial symbionts are known to strongly affect many aspects of insect biology, we lack data on their effects on populations or community processes, or on insects' evolutionary responses at different timescales. How these effects change as the anthropogenic effects on ecosystems intensify is an area of intense research. Recent developments in sequencing and bioinformatics permit cost-effective microbial diversity surveys, tracking symbiont transmission, and identification of functions across insect populations and multi-species communities. In this review, we explore how different functional categories of symbionts can influence insect life-history traits, how these effects could affect insect populations and their interactions with other species, and how they may affect processes and patterns at the level of entire communities. We argue that insect-associated microbes should be considered important drivers of insect response and adaptation to environmental challenges and opportunities. We also outline the emerging approaches for surveying and characterizing insect-associated microbiota at population and community scales. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Joint transcriptomic and metabolomic analysis provides new insights into drought resistance in watermelon (Citrullus lanatus)

IntroductionWatermelon is an annual vine of the family Cucurbitaceae. Watermelon plants produce a fruit that people love and have important nutritional and economic value. With global warming and deterioration of the ecological environment, abiotic stresses, including drought, have become important factors that impact the yield and quality of watermelon plants. Previous research on watermelon drought resistance has included analyzing homologous genes based on known drought-responsive genes and pathways in other species.MethodsHowever, identifying key pathways and genes involved in watermelon drought resistance through high-throughput omics methods is particularly important. In this study, RNA-seq and metabolomic analysis were performed on watermelon plants at five time points (0 h, 1 h, 6 h, 12 h and 24 h) before and after drought stress.ResultsTranscriptomic analysis revealed 7829 differentially expressed genes (DEGs) at the five time points. The DEGs were grouped into five clusters using the k-means clustering algorithm. The functional category for each cluster was annotated based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database; different clusters were associated with different time points after stress. A total of 949 metabolites were divided into 10 categories, with lipids and lipid-like molecules accounting for the most metabolites. Differential expression analysis revealed 22 differentially regulated metabolites (DRMs) among the five time points. Through joint analysis of RNA-seq and metabolome data, the 6-h period was identified as the critical period for watermelon drought resistance, and the starch and sucrose metabolism, plant hormone signal transduction and photosynthesis pathways were identified as important regulatory pathways involved in watermelon drought resistance. In addition, 15 candidate genes associated with watermelon drought resistance were identified through joint RNA-seq and metabolome analysis combined with weighted correlation network analysis (WGCNA). Four of these genes encode transcription factors, including bHLH (Cla97C03G068160), MYB (Cla97C01G002440), HSP (Cla97C02G033390) and GRF (Cla97C02G042620), one key gene in the ABA pathway, SnRK2-4 (Cla97C10G186750), and the GP-2 gene (Cla97C05G105810), which is involved in the starch and sucrose metabolism pathway.DiscussionIn summary, our study provides a theoretical basis for elucidating the molecular mechanisms underlying drought resistance in watermelon plants and provides new genetic resources for the study of drought resistance in this crop.

Influences of Ipomoea batatas Anti-Cancer Peptide on Tomato Defense Genes.

This study investigates the impact of IbACP (Ipomoea batatas anti-cancer peptide) on defense-related gene expression in tomato leaves, focusing on its role in plant defense mechanisms. Previously, IbACP was isolated from sweet potato leaves, and it was identified as a peptide capable of inducing an alkalinization response in tomato suspension culture media. Additionally, IbACP was found to regulate the proliferation of human pancreatic adenocarcinoma cells. Elucidate IbACP's molecular influence on defense-related gene expression in tomato leaves using next-generation sequencing analysis. To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP for durations ranging from 0 h (control) to 24 h. IbACP induced jasmonic acid-related genes (LoxD and AOS) at 2 h, with a significant up-regulation of salicylic acid-dependent gene NPR1 at 24 h. This suggested a temporal antagonistic effect between jasmonic acid and salicylic acid during the early hours of IbACP treatment. Downstream ethylene-responsive regulator genes (ACO1, ETR4, and ERF1) were consistently down-regulated by IbACP at all times. Additionally, IbACP significantly up-regulated the gene expressions of suberization-associated anionic peroxidases (TMP1 and TAP2) at all time points, indicating enhanced suberization of the plant cell wall to prevent pathogen invasion. IbACP enhances the synthesis of defense hormones and up-regulates downstream defense genes, improving the plant's resistance to biotic stresses.

Abstract PO4-28-01: Molecular profiling revealed activation of cytokine signaling and suppression of lipid metabolism as the hallmarks of doxorubicin-resistant TNBC

Abstract Background: Chemotherapeutic resistance observed in triple-negative breast cancer (TNBC) poses a substantial clinical hurdle, emphasizing the imperative to enhance our comprehension of the underlying mechanisms with the aim of potentially mitigating or reversing this phenomenon. Methods: Doxorubicin-resistant (DoxR) TNBC models (MDA-MB-231 and BT-549) were established through continuous exposure to increasing concentrations of doxorubicin. RNA-Seq was conducted using the Illumina platform, while bioinformatics analyses were performed using CLC genomics workbench 20.2 and iDEP.91. Colony forming unit (CFU), flow cytometry and fluorescent microscopy were used to assess cell proliferation, cell cycle distribution, and cell death, respectively. Western blotting was used to confirm the expression and phosphorylation of protein targets. Ingenuity pathway analysis (IPA) and STRING database v 11.5 were used for network and pathway analyses, while Kaplan-Meier Plotter was used for survival analyses. Results: Herein, we provide a comprehensive functional and transcriptomic characterization of DoxR TNBC models, revealing multiple affected signaling networks and functional categories. The defense and immune response, response to stress, response to cytokine and external stimulus and cytokine-mediated signaling pathways were among the top activated, while suppression of cholesterol, sterol and lipid biosynthesis and metabolism were the hallmarks of DoxR cells. Upstream regulator analysis revealed IL-1B cytokine network activation in DoxR cells. Concordantly, disease and function analysis on the downregulated genes in DoxR TNBC cells revealed the most pronounced enrichment in pathways associated with cell invasion, colony formation, as well as lipid and carbohydrate metabolism. A number of upregulated genes were validated by qRT-PCR, which correlated with unfavorable overall survival (OS). Functionally, DoxR cells exhibited remarkable suppression of cell proliferation, as evidenced by diminished CFU potential, sphere formation and growth under 3D organoid culture, and cell migration. Although DoxR TNBC cells exhibited a slow cell cycling under normal culture conditions, wild-type TNBC cells exhibited remarkable arrest in the G2M phase when exposed to doxorubicin, which was less evident in DoxR TNBC models, suggesting DoxR cells undergo a quiescent state in response to chemotherapeutic challenge. In agreement with those data, increased phosphorylation of CHK2 and p53 proteins was remarkable in DoxR cells, thus promoting cellular dormancy. Conclusion: Our data revealed cellular dormancy and suppression of lipid metabolism as the hallmark associated with doxorubicin-resistant TNBC cells. On the other hand, cytokine signaling and stress response were the most enriched functional categories in DoxR TNBC cells. Therapeutic targeting to reverse the quiescent state or suppression of cytokine signaling networks could enhance the efficacy of doxorubicin-based therapeutics. Citation Format: Vishnubalaji Radhakrishnan, Nehad Alajez. Molecular profiling revealed activation of cytokine signaling and suppression of lipid metabolism as the hallmarks of doxorubicin-resistant TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-28-01.

Abstract PO3-04-01: Population Pharmacokinetics of trastuzumab deruxtecan (T-DXd) in HER2-positive breast cancer subjects: analyses across 12 Phase 1-3 studies

Abstract Background: T-DXd, an antibody-drug conjugate composed of a humanized anti-HER2 monoclonal antibody and a topoisomerase I inhibitor payload, is approved for adult patients with unresectable or metastatic HER2-positive (HER2+) BC administered T-DXd 5.4 mg/kg Q3W with a prior anti-HER2–based therapy either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. The objective of this analysis was to present pharmacokinetic (PK) characterization of T-DXd and DXd in patients with advanced/metastatic HER2-positive breast cancer from a pooled data source of 12 phase 1 to 3 clinical trials. Methods: Data from subjects with HER2-positive breast cancer and other solid tumors enrolled in studies DS8201-A-J101, DS8201-A-J102, DS8201-A-A103, DS8201-A-A104, DS8201-A-U201, DS8201-AJ202, DS8201-A-U205, DS8201-A-U204, DS8201-A-U206, DS8201-A-U301, DS8201-A-U302, and DS8201-A-U303 were used for this analysis. A population PK (PopPK) analysis was performed using nonlinear mixed effects modeling approach using NONMEM® (version 7.4.3). The effect of significant covariates was evaluated by univariate and multivariate analyses on steady-state exposure of T-DXd and DXd. Results: Data across T-DXd doses 0.8 to 8 mg/kg with 2216 subjects were included. The PK of T-DXd and DXd were adequately described by PopPK analysis based on standard model diagnostic techniques. T-DXd elimination clearance and volume of distribution of central and peripheral compartments were estimated at 0.402 L/day, 2.68 L and 5.91 L, respectively. DXd elimination clearance was estimated at 18.4 L/hour. Covariates previously detected to be statistically significant (cancer type, tumor size, albumin, race-country, body weight and sex for T-DXd; age, cancer type, AST, total bilirubin, ritonavir or itraconazole use, race-country, formulation and body weight for DXd) were retained in the PopPK model. No new covariates were identified as statistically significant in the PopPK analysis. All covariates were contained within the 0.8 to 1.25 exposure ratio interval in T-DXd and DXd steady-state area under the concentration-time curve (AUC), indicating no clinically meaningful effect, except for subjects with high body weight (90 kg; 95th percentile) showing a 28% and 26% higher T-DXd and DXd AUC, respectively, relative to a BC subject with median body weight of 60 kg. None of these changes were clinically meaningful based on exposure-response analyses of efficacy and safety endpoints. T-DXd and DXd post hoc exposure estimates in all BC subjects (HER2-positive and HER2-low) as well as BC subjects with HER2- positive were comparable across hepatic function, renal function, region, race-country and line of therapy. Conclusions: Similar T-DXd and DXd exposures were obtained for the recommended dosing of 5.4 mg/kg Q3W T-DXd in BC subjects across categories of hepatic function, renal function, region, race-country, HER2 status, and line of therapy. Citation Format: Claire Li, Stefanie henning, Kashyap Patel, Katrina Hui, Gerly van der Vleuten, malaz Abutarif, Tushar Garimella, Amit Khatri. Population Pharmacokinetics of trastuzumab deruxtecan (T-DXd) in HER2-positive breast cancer subjects: analyses across 12 Phase 1-3 studies [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-01.

Protein function prediction through multi-view multi-label latent tensor reconstruction

BackgroundIn last two decades, the use of high-throughput sequencing technologies has accelerated the pace of discovery of proteins. However, due to the time and resource limitations of rigorous experimental functional characterization, the functions of a vast majority of them remain unknown. As a result, computational methods offering accurate, fast and large-scale assignment of functions to new and previously unannotated proteins are sought after. Leveraging the underlying associations between the multiplicity of features that describe proteins could reveal functional insights into the diverse roles of proteins and improve performance on the automatic function prediction task.ResultsWe present GO-LTR, a multi-view multi-label prediction model that relies on a high-order tensor approximation of model weights combined with non-linear activation functions. The model is capable of learning high-order relationships between multiple input views representing the proteins and predicting high-dimensional multi-label output consisting of protein functional categories. We demonstrate the competitiveness of our method on various performance measures. Experiments show that GO-LTR learns polynomial combinations between different protein features, resulting in improved performance. Additional investigations establish GO-LTR’s practical potential in assigning functions to proteins under diverse challenging scenarios: very low sequence similarity to previously observed sequences, rarely observed and highly specific terms in the gene ontology.ImplementationThe code and data used for training GO-LTR is available at https://github.com/aalto-ics-kepaco/GO-LTR-prediction.

Proteomics profiling reveals the detoxification and tolerance behavior of two bread wheat (Triticum aestivum L.) varieties under arsenate stress

Arsenic (As) contaminated irrigation water caused a significant buildup of its level in the agricultural soil and edible tissues of wheat. High levels of As negatively impact grain quality, wheat yield, and human health consequently. It is still unknown how wheat varieties respond to As stress at the proteomic level. Therefore, the present study aimed to deliver mechanistic details regarding the role of proteins in tolerance mechanism against As stress. Two wheat varieties (BARANI-70 and NARC-2009) were exposed to arsenate treatment (200µM) in a hydroponic experiment to evaluate the impacts of arsenic stress using proteomics. Roots of both varieties were used for protein extraction, digestion, and LC-MS/MS analysis to identify differentially abundant proteins (DAPs). Furthermore, various bioinformatic tools were used to study subcellular localization, functional categories, and pathway analysis. The findings identified 67 DAPs in BARANI-70 (up-regulated=56; down-regulated=11) and 89 DAPs in NARC-2009 (up-regulated=34; down-regulated=55). Subcellular localization revealed significant up-regulation of DAPs in mitochondria and chloroplast for BARANI-70 but down-regulation in NARC-2009 under As stress. Functional analysis revealed significant upregulation of DAPs for glutathione, peroxidase, glutathione peroxidase, lactoylglutathione lyase, and glutathione-s-transferase in BARANI-70. Pathway analysis showed regulation of DAPs involved in tetrapyrrole biosynthesis and glycolysis-TCA particularly in BARANI-70 compared to NARC-2009. Furthermore, BARANI-70 showed better growth response under As stress compared to NARC-2009. Thus, better synthesis of stress-responsive DAPs and important pathways in BARANI-70 contributed towards its tolerance against As stress. The present research supports the use of tolerant varieties and identified protein biomarkers to enhance crop resilience against As stress.

Proteomic profiling of tumor microenvironment and prognosis risk prediction in stage I lung adenocarcinoma

ObjectivesWith the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. Materials and methodsWe collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. ResultsThe analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. ConclusionThe risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.

Functional Genotype-Phenotype Associations in Recessive Dystrophic Epidermolysis Bullosa

Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB) have been difficult to elucidate. To investigate RDEB genotype-phenotype associations and explore a functional approach to genotype classification. Clinical examination and genetic testing of RDEB subjects, including assessment of clinical disease by RDEB subtype and extent of blistering. Genotypes were evaluated according to each variant's effect on type VII collagen (C7) function per updated literature, and subsequently categorized by degree of impact on C7 function as low-impact (splice/missense, missense/missense), medium-impact (premature termination codon [PTC]/missense, splice/splice), and high-impact (PTC/PTC, PTC/splice). Genotype-phenotype associations were investigated using Kruskal-Wallis and Fisher's exact tests, and age-adjusted regressions. 83 participants were included. High-impact variants were associated with worse RDEB subtype and clinical disease, including increased prevalence of generalized blistering (55.6% for low-impact vs. 72.7% medium-impact vs. 90.4% high-impact variants, p=0.002). In age-adjusted regressions, participants with high-impact variants had 40.8-fold greater odds of squamous cell carcinoma compared to low-impact variants (p=0.02), and 5.7-fold greater odds of death compared to medium-impact variants (p=0.05). Cross-sectional design. Functional genotype categories may stratify RDEB severity; high-impact variants correlated with worse clinical outcomes. Further validation in larger cohorts is needed.

Effects of salinity stress on physiological behavior, respiratory metabolism, and intestinal transcriptome of juvenile Stichopus monotuberculatus

This study investigated the impacts of salinity stress on the physiological behavior, respiratory metabolism, and transcriptome of artificially cultured juvenile Stichopus monotuberculatus (S. monotuberculatus) (with a body weight of 3.23 ± 0.60 g). S. monotuberculatus individuals cultured in artificial seawater were transferred to artificial seawater with salinities of 20‰, 30‰, and 40‰ for salinity stress treatment. The physiological behavior of S. monotuberculatus was observed, and their ammonia discharge rates, oxygen consumption rates, and oxygen/nitrogen (O/N) ratios were measured. After 24 h of stress, the intestines of S. monotuberculatus were collected for transcriptome sequencing. The results showed that both hyper-salinity and hypo-salinity stresses significantly affected the physiological status of S. monotuberculatus. The oxygen consumption and ammonia discharge rates of the hyper-salinity group (40‰) and hypo-salinity (20‰) group were remarkably higher than those of the control group (P<0.05), and the O/N ratios of the two groups were significantly lower than those of the control group (P<0.05). Sequencing identified a total of 3840 differentially expressed genes (DEGs) from the salinity-stress groups and the control group. GO analysis revealed that DEGs were mainly enriched in biological processes, cellular components, and molecular functional categories, with the highest enrichment observed in cellular processes, metabolic processes, membranes, binding, and catalytic activities. KEGG analysis showed that the DEGs of hyper-salinity and hypo-salinity groups were enriched in different secondary pathways, with the expressions of related genes significantly upregulated, indicating that S. monotuberculatus may adapt to hyper-salinity and hypo-salinity environments through various regulatory mechanisms. The results verify that salinity stress significantly affects the physiological behavior and respiratory metabolism of S. monotuberculatus. S. monotuberculatus respond to hyper-salinity and hypo-salinity stresses by increasing protein consumption and adopting different adaptation mechanisms. Furthermore, S. monotuberculatus exhibits stronger tolerance to hypo-salinity environments compared to hyper-salinity ones.

Function and Form in Territorial Planning: The Case of Lens in the Mining Basin in Nord and Pas-de-Calais – France

This article purposes to engage in a discussion regarding the transformations and restructuring of the city of Lens, located in the department of Pas-de-Calais, in the administrative region of Hauts-de-France, northern France. This discussion pertains to the spatial transformations of the categories of form and function during the evolution of industrial capitalism and, subsequently, globalization. The process of "Territorial Reconversion" implemented in the area, through state planning, from the 1960s to 1990 (the year of the closure of the last coal mine), aimed to alter the region's specialization in response to the serious issues of unemployment and economic recession. Thus, through the establishment of infrastructure and urban remodeling, the French state, in association with policies from the European Union, involving private companies and civil organizations in the region, organized itself to transform the area by changing the economic profile linked to mining and textile production to more dynamic and productive activities. These strategies influenced the transformations of the urban space of the city of Lens, reshaping it towards cultural activities (especially music and cinema workshops) and tourist activities. Among the latter, the installation of a branch of the Louvre Museum stands out. This article aims to reflect on these transformations in Lens, based on the analysis of the introduction of new forms and functions, as well as the re-signification of old forms enveloped by new functions.

FEV1 and FVC as robust risk factors for cardiovascular disease and mortality: Insights from a large population study

IntroductionData is limited on influence of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in a large adult population, including individuals with normal spirometry at baseline. MethodsUsing the UK Biobank cohort, a multivariable Cox regression analysis was conducted on 406,424 individuals to examine the association between FEV1 and FVC, categorized into three groups based on their percentage of predicted values (%pred) (≥80, 60–80 and < 60), and overall mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure over approximately 12.5 years. Moreover, a subgroup analysis was conducted on 295,459 individuals who had normal spirometry. ResultsReduced FEV1 and FVC %pred values were associated with an elevated risk across all studied outcomes. Individuals with the lowest FEV1 and FVC %pred values (<60 %) exhibited HR of 1.83 (95 % CI 1.74–1.93) and 1.98 (95 % CI 1.76–2.22) for overall mortality, and 1.96 (95 % CI 1.83–2.1) and 2.26 (95 % CI 1.94–2.63) for cardiovascular mortality. Moreover, a graded association was observed between lower FEV1 and FVC %pred, even among never smokers and individuals with normal spirometry at baseline. DiscussionReduced FEV1 and FVC represent robust risk factors for cardiovascular disease and mortality. The fact that the increased risk was evident also at FEV1 and FVC levels exceeding 80 %pred challenges the contemporary classification of lung function categories and the notion that the entire FEV1- and FVC-range above 80 % of predicted represents a normal lung function.

Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study.

Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional communication on the brain-gut axis. However, the specific mechanism of intestinal diseases and vascular dementia (VD) remains unclear. We designed this study especially, to further clarify the connection between VD and inflammatory bowel disease (IBD) from bioinformatics analyses. We downloaded Gene expression profiles for VD (GSE122063) and IBD (GSE47908, GSE179285) from the Gene Expression Omnibus (GEO) database. Then individual Gene Set Enrichment Analysis (GSEA) was used to confirm the connection between the two diseases respectively. The common differentially expressed genes (coDEGs) were identified, and the STRING database together with Cytoscape software were used to construct protein-protein interaction (PPI) network and core functional modules. We identified the hub genes by using the Cytohubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify pathways of coDEGs and hub genes. Subsequently, receiver operating characteristic (ROC) analysis was used to identify the diagnostic ability of these hub genes, and a training dataset was used to verify the expression levels of the hub genes. An alternative single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration between coDEGs and immune cells. Finally, the correlation between hub genes and immune cells was analyzed. We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, and BTK. The functional categories of hub genes enrichment analysis were mainly involved in the regulation of immune function and neuroinflammatory response. Compared to the healthy controls, abnormal infiltration of immune cells was found in VD and IBD. We also found the correlation between 8 shared hub genes and immune cells. This study suggests that IBD may be a new risk factor for VD. The 8 hub genes may predict the IBD complicated with VD. Immune-related coDEGS may be related to their association, which requires further research to prove.

Construct validity, responsiveness and minimal important difference of the cumulated ambulation score in older adults with hip fracture in sub-acute rehabilitation facility.

To assess the construct validity, responsiveness and minimal important difference of the cumulated ambulation score in patients with hip fracture in sub-acute rehabilitation facility. Observational, prospective, monocenter, cohort study. Rehabilitation Institute. 456 older adults with hip fracture (≥65 years) admitted for inpatient rehabilitation. Cumulated ambulation score, functional independence measure and functional ambulation category were collected at admission and discharge. Construct validity and responsiveness were assessed through hypothesis testing and minimal important difference was determined using the anchor-based method; floor and ceiling effects were also assessed. The cumulated ambulation score showed strong correlations with the functional independence measure and functional ambulation category scores at both admission and discharge, satisfying all the hypotheses for construct validity. The effect size of cumulated ambulation score was 1.63. Changes in cumulated ambulation score had a moderate-to-strong correlation with changes of other instruments and were able to discriminate patients improved from those not-improved, and patients classified as independent ambulators from those dependent. A ceiling effect was found only at discharge. The estimated minimal important difference was 2 points. The cumulated ambulation score showed high levels of construct validity and responsiveness according to the hypothesis testing. A two points improvement at the end of rehabilitation was found to be clinically important in people with hip fracture in the sub-acute phase. The ceiling effect found at discharge suggested the limitation of the scale in assessing people with a partially recovered autonomy in performing postural changes and gait.

OA01 Cluster medicine: the role of genetics for identifying shared biological pathways between rheumatoid arthritis and common comorbidities for targeting treatments

Abstract Background/Aims Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with significant pain and disability, as well as increased risk of comorbidities. These comorbidities, such as coronary artery disease, stroke, heart failure and type 2 diabetes, often form predictable clusters highlighting the importance of common disease mechanisms. Identifying these clusters, and the underlying shared mechanisms, is key to the concept of cluster medicine which aims to take a more systemic approach to treating comorbidity. It is hypothesised that inflammatory processes in RA promote the pathogenesis of these comorbid diseases, which typically occur at an earlier stage of life than in the general population. However, few studies have investigated the degree of shared genetic susceptibility implicated across these traits. The present study aimed to identify and characterise pleiotropic loci and shared biological pathways involved in the pathogenesis of RA and cardiometabolic disorders. Methods European-only GWAS summary statistics were collected for RA (seropositive, seronegative, and overall) and seven cardiometabolic traits, including ischemic stroke, any stroke, heart failure, coronary artery disease, hypertension, atrial fibrillation, and type 2 diabetes. Cross-trait linkage disequilibrium score regression was employed to estimate the degree of genetic correlation (rg) between all pairs of traits. Subset-based meta-analysis was performed using the R package ASSET to identify pleiotropic single nucleotide polymorphisms (SNPs). Pleiotropic SNPs were assigned to genes based on positional and eQTL mapping. Prioritised genes were tested for over-representation in functional categories and biological pathways in gene sets obtained from MsigDB and WikiPathways using the hypergeometric test loci. Gene mapping and enrichment analyses were conducted in FUMA. Results RA showed significant positive genetic correlation with all cardiometabolic traits, with the seronegative subtype showing greater correlation than the seropositive subtype. Correlations between RA and cardiometabolic phenotypes ranged from 0.11 - 0.38, the strongest of which was between seronegative RA and heart failure (rg = 0.38, P = 2.6e-07). A total of 67 lead SNPs were identified as potentially pleiotropic. Pleiotropic SNPs were mapped to genes including IL6R, PTPN11, ATXN2, PLCL1 and SOX6. Pathway enrichment analyses revealed that mapped genes were primarily involved in inflammatory signalling pathways, involving interleukins, TNF-α and interferon (gamma and alpha) response. Conclusion This study provides evidence for pleiotropy across RA and cardiometabolic traits, whereby inherited genetic variants predispose to aberrant cytokine signalling, thus conferring risk to multiple diseases where inflammation is a key driver of pathogenesis. Disclosure M. Stoves: None. M. Soomro: None. S. Zhao: None. D. Plant: None. A. Barton: None. J. Bowes: None.

Exercise Training Attenuates the Muscle Mitochondria Genomic Response to Bed Rest.

Exercise training during the National Aeronautics and Space Administration (NASA) 70-day bed rest study effectively counteracted the decline in aerobic capacity, muscle mass, strength, and endurance. We aimed to characterize the genomic response of the participants' vastus lateralis (VL) on day 64 of bed rest with and without exercise countermeasures. Twenty-two healthy young males were randomized into three groups: 1) bed rest only (n = 7), 2) bed rest + aerobic (6 d/wk) and resistance training (3 d/wk) on standard equipment (n = 7), and 3) bed rest + aerobic and resistance training using a flywheel device (n = 8). The VL gene and microRNA microarrays were analyzed using GeneSpring GX 14.9.1. Bed rest significantly altered the expression of 2113 annotated genes in at least one out of the three study groups (fold change (FC) > 1.2; P < 0.05). Interaction analysis revealed that exercise attenuated the bed rest effect of 511 annotated genes (FC 1.2, P < 0.05). In the bed rest only group, a predominant downregulation of genes was observed while in the two exercise groups there was a notable attenuation or reversal of this effect, with no significant differences between the two exercise modalities. Enrichment analysis identified functional categories and gene pathways, many of them related to the mitochondria. Additionally, bed rest significantly altered the expression of 35 microRNAs (FC > 1.2, P < 0.05) with no difference between the three groups. Twelve are known to regulate some of the mitochondrial-related genes that were altered following bed rest. Mitochondrial gene expression was a significant component of the molecular response to long-term bed rest. While exercise attenuated the FC in the downregulation of many genes, it did not completely counteract all the molecular consequences.

Ten principles for responsible quantum innovation

This paper proposes a set of guiding principles for responsible quantum innovation. The principles are organized into three functional categories: safeguarding, engaging, and advancing (SEA), and are linked to central values in responsible research and innovation (RRI). Utilizing a global equity normative framework and literature-based methodology, we connect the quantum-SEA categories to promise and perils specific to quantum technology (QT). The paper operationalizes the responsible QT framework by proposing ten actionable principles to help address the risks, challenges, and opportunities associated with the entire suite of second-generation QTs, which includes the quantum computing, sensing, simulation, and networking domains. Each quantum domain has different technology readiness levels, risks, and affordances, with sensing and simulation arguably being closest to market entrance. Our proposal aims to catalyze a much-needed interdisciplinary effort within the quantum community to establish a foundation of quantum-specific and quantum-tailored principles for responsible quantum innovation. The overarching objective of this interdisciplinary effort is to steer the development and use of QT in a direction not only consistent with a values-based society but also a direction that contributes to addressing some of society’s most pressing needs and goals.