Elevated Scores Research Articles

Analysis of risk factors for changes of renal artery resistance indexes in gout patients by ultrasound colour Doppler.

Gout may disturb renal hemodynamics by promoting uric acid deposition; however, this relationship has not been elucidated with adequate clinical evidence. In this study, we measured the renal artery resistance index (ARI) in patients with gout to identify the risk factors and establish predictive models for elevated renal ARI in these patients. Renal artery ultrasound examination was performed in 235 primary gout patients and 50 healthy controls (HCs); subsequently, their renal interlobar ARI (RIARI), renal segmental ARI (RSARI) and overall intrarenal ARI (OIARI) were recorded. Each ARI > 0.7 was considered elevated. RIARI, RSARI and OIARI were higher in patients with gout than in HCs (all P < 0.001). Nineteen (8.1%), 24 (10.2%) and 18 (7.7%) patients had elevated RIARI, RSARI and OIARI scores, respectively. Multivariate logistic regression analyses disclosed that: age ≥ 60 years (P = 0.000), abnormal beta2 microglobulin (β2MG) (P = 0.028), and abnormal high-density lipoprotein cholesterol (HDLC) (P = 0.030) were independently associated with elevated RIARI; age ≥ 60 years (P = 0.000), and abnormal β2MG (P = 0.013) were independently related to elevated RSARI; abnormal total protein (TP) (P = 0.014) were independently linked with elevated OIARI in gout patients. Consequently, predictive models for elevated ARI were established using nomograms based on the aforementioned independent risk factors, which showed a satisfactory value for estimating elevated RIARI [area under the curve (AUC):0.929], RSARI (AUC: 0.926) and OIARI (AUC: 0.660) in patients with gout, as validated by receiver operating characteristic curves. Renal ARI were elevated in patients with gout, whose independent risk factors included older age and abnormal β2MG, HDLC and TP levels.

Clinical and genetic associations of asymmetric apical and septal left ventricular hypertrophy.

Increased left ventricular mass has been associated with adverse cardiovascular outcomes including incident cardiomyopathy and atrial fibrillation. Such associations have been studied in relation to total left ventricular hypertrophy, while the regional distribution of myocardial hypertrophy is extremely variable. The clinically significant and genetic associations of such variability require further study. Here, we use deep learning-derived phenotypes of disproportionate patterns of hypertrophy, namely, apical and septal hypertrophy, to study genome-wide and clinical associations in addition to and independent from total left ventricular mass within 35 268 UK Biobank participants. Using polygenic risk score and Cox regression, we quantified the relationship between incident cardiovascular outcomes and genetically determined phenotypes in the UK Biobank. Adjusting for total left ventricular mass, apical hypertrophy is associated with elevated risk for cardiomyopathy and atrial fibrillation. Cardiomyopathy risk was increased for subjects with increased apical or septal mass, even in the absence of global hypertrophy. We identified 17 genome-wide associations for left ventricular mass, 3 unique associations with increased apical mass, and 3 additional unique associations with increased septal mass. An elevated polygenic risk score for apical mass corresponded with an increased risk of cardiomyopathy and implantable cardioverter-defibrillator implantation. Apical and septal mass may be driven by genes distinct from total left ventricular mass, suggesting unique genetic profiles for patterns of hypertrophy. Focal hypertrophy confers independent and additive risk to incident cardiovascular disease. Our findings emphasize the significance of characterizing distinct subtypes of left ventricular hypertrophy. Further studies are needed in multi-ethnic cohorts.

Assessing Avoidant/Restrictive Food Intake Disorder (ARFID) Symptoms Using the Nine Item ARFID Screen in >9000 Swedish Adults With and Without Eating Disorders.

The Nine Item ARFID Scale (NIAS) is a widely used measure assessing symptoms of avoidant/restrictive food intake disorder (ARFID). Previous studies suggest that individuals with eating disorders driven by shape/weight concerns also have elevated scores on the NIAS. To further describe NIAS scores among individuals with diverse current and previous eating disorders, we characterized NIAS scores in a large sample of individuals with eating disorders and evaluated overlap in symptoms measured by the NIAS and the Eating Disorder Examination-Questionnaire (EDE-Q) version 6.0. Our sample comprised 9148 participants from the Eating Disorders Genetics Initiative Sweden (EDGI-SE), who completed surveys including NIAS and EDE-Q. NIAS scores were calculated and compared by eating disorder diagnostic group using descriptive statistics and linear models. Participants with current anorexia nervosa demonstrated the highest mean NIAS scores and had the greatest proportion (57.0%) of individuals scoring above a clinical cutoff on at least one of the NIAS subscales. Individuals with bulimia nervosa, binge-eating disorder, and other specified feeding or eating disorder also demonstrated elevated NIAS scores compared to individuals with no lifetime history of an eating disorder (ps < 0.05). All subscales of the NIAS showed small to moderate correlations with all subscales of the EDE-Q (rs = 0.26-0.40). Our results substantiate that individuals with eating disorders other than ARFID demonstrate elevated scores on the NIAS, suggesting that this tool is inadequate on its own for differentiating ARFID from shape/weight-motivated eating disorders. Further research is needed to inform clinical interventions addressing the co-occurrence of ARFID-related drivers and shape/weight-related motivation for dietary restriction.

Establishment of a chemokine-based prognostic model and identification of CXCL10+ M1 macrophages as predictors of neoadjuvant therapy efficacy in colorectal cancer.

Although neoadjuvant therapy has brought numerous benefits to patients, not all patients can benefit from it. Chemokines play a crucial role in the tumor microenvironment and are closely associated with the prognosis and treatment of colorectal cancer. Therefore, constructing a prognostic model based on chemokines will help risk stratification and providing a reference for the personalized treatment. Employing LASSO-Cox predictive modeling, a chemokine-based prognostic model was formulated, harnessing the data from TCGA and GEO databases. Then, our exploration focused on the correlation between the chemokine signature and elements such as the immune landscape, somatic mutations, copy number variations, and drug sensitivity. CXCL10+M1 macrophages identified via scRNA-seq. Monocle2 showed cell pseudotime trajectories, CellChat characterized intercellular communication. CytoTRACE analyzed neoadjuvant therapy stemness, SCENIC detected cell type-specific regulation. Lastly, validation was performed through multiplex immunofluorescence experiments. A model based on 15 chemokines was constructed and validated. High-risk scores correlated with poorer prognosis and advanced TNM and clinical stages. Individuals presenting elevated risk scores demonstrated an increased propensity towards the development of chemotherapy resistance. Subsequent scRNA-seq data analysis indicated that patients with higher presence of CXCL10+ M1 macrophages in tumor tissues are more likely to benefit from neoadjuvant therapy. We developed a chemokine-based prognostic model by integrating both single-cell and bulk RNA-seq data. Furthermore, we revealed epithelial cell heterogeneity in neoadjuvant outcomes and identified CXCL10+ M1 macrophages as potential therapy response predictors. These findings could significantly contribute to risk stratification and serve as a key guide for the advancement of personalized therapeutic approaches.

Continuous Monitoring of Heart Rate Variability in Free-Living Conditions Using Wearable Sensors: Exploratory Observational Study.

Wearable physiological monitoring devices are promising tools for remote monitoring and early detection of potential health changes of interest. The widespread adoption of such an approach across communities and over long periods of time will require an automated data platform for collecting, processing, and analyzing relevant health information. In this study, we explore prospective monitoring of individual health through an automated data collection, metrics extraction, and health anomaly analysis pipeline in free-living conditions over a continuous monitoring period of several months with a focus on viral respiratory infections, such as influenza or COVID-19. A total of 59 participants provided smartwatch data and health symptom and illness reports daily over an 8-month window. Physiological and activity data from photoplethysmography sensors, including high-resolution interbeat interval (IBI) and step counts, were uploaded directly from Garmin Fenix 6 smartwatches and processed automatically in the cloud using a stand-alone, open-source analytical engine. Health risk scores were computed based on a deviation in heart rate and heart rate variability metrics from each individual's activity-matched baseline values, and scores exceeding a predefined threshold were checked for corresponding symptoms or illness reports. Conversely, reports of viral respiratory illnesses in health survey responses were also checked for corresponding changes in health risk scores to qualitatively assess the risk score as an indicator of acute respiratory health anomalies. The median average percentage of sensor data provided per day indicating smartwatch wear compliance was 70%, and survey responses indicating health reporting compliance was 46%. A total of 29 elevated health risk scores were detected, of which 12 (41%) had concurrent survey data and indicated a health symptom or illness. A total of 21 influenza or COVID-19 illnesses were reported by study participants; 9 (43%) of these reports had concurrent smartwatch data, of which 6 (67%) had an increase in health risk score. We demonstrate a protocol for data collection, extraction of heart rate and heart rate variability metrics, and prospective analysis that is compatible with near real-time health assessment using wearable sensors for continuous monitoring. The modular platform for data collection and analysis allows for a choice of different wearable sensors and algorithms. Here, we demonstrate its implementation in the collection of high-fidelity IBI data from Garmin Fenix 6 smartwatches worn by individuals in free-living conditions, and the prospective, near real-time analysis of the data, culminating in the calculation of health risk scores. To our knowledge, this study demonstrates for the first time the feasibility of measuring high-resolution heart IBI and step count using smartwatches in near real time for respiratory illness detection over a long-term monitoring period in free-living conditions.

RAD51 High-Expressed Hepatocellular Carcinomas Are Associated With High Cell Proliferation

IntroductionRAD51 is a pivotal DNA repair gene managing double-stranded DNA break recognition and repair. RAD51 high expression was associated with adverse outcomes in other cancer types. This study aims to investigate the tumor microenvironment and immune landscape in the RAD51 high-expressed Hepatocellular Carcinoma (HCCs). MethodsA total of 467 patients from two large independent cohorts with clinical and transcriptomic data were obtained. The cohort was dichotomized based on the median RAD51 gene expression. xCell and Gene Set Enrichment Analysis (GSEA) were used. ResultsRAD51 high-expressed HCCs were associated with worse recurrence-free, progression-free, disease-specific, and overall survival (all P < 0.05). While RAD51 high-expressed HCCs were associated with intratumoral heterogeneity, homologous recombination deficiency, and fraction altered scores, mutation or neoantigens were not increased in this group. xCell analysis demonstrated inconsistent immune cell infiltration between two cohorts. Cytolytic activity as well as GSEA with immune-related gene sets also demonstrated inconsistent results between two cohorts as well. On the other hand, RAD51 expression was significantly increased in higher-grade tumors, larger tumors, and higher clinical stages. RAD51 high-expressed HCCs were found to have elevated proliferation score. Furthermore, GSEA exhibited significant enrichment of all the cell proliferation–related gene sets in the Hallmark collection, including E2F targets, G2M checkpoint, Mitotic spindle, MYC targets, and MTORC1 signaling consistently in both cohorts (all false discovery rate < 0.25). ConclusionsRAD51 high-expressed HCCs were associated with worse survival and with increased cell proliferation and were not necessarily associated with immune infiltration or inflammation.

Comparative Investigation of Differential Mood Responses among Elite, Non-Elite, and Non-Athletes in Total Lockdown

The onset of the COVID-19 global health crisis, marked by stringent restrictions on training routines and sudden cancellations of competitive events, precipitated abrupt and radical transformations within the sporting landscape. The emergency alert prompted governments worldwide to enforce various lockdown measures to curb the escalation of the viral outbreak. Recognising the potential psychological repercussions of these circumstances, a rapid assessment of mood states as well-being indicators was conducted during the initial months of the lockdown in the Philippines. A cross-sectional study using Tilly’s (1984) variation-finding approach was undertaken to distinguish mood profiles between athletes of different competitive tiers and between athletes and non-athletes. Employing the 16-item version of the Profile of Mood States (POMS-16), mood responses were collected and compared across 705 elite athletes, 1,702 non-elite athletes, and 1,246 non-athletes. Analysis of mean patterns revealed that elite athletes consistently reported greater levels of dejection/anxiety, fatigue, irritability, vigour, and overall mood disturbance than did their non-elite and non-athlete counterparts. The findings affirm the substantial disparities in mood states between athletes of different competitive tiers and between athletes and non-athletes during the pandemic. Nonetheless, despite the elevated scores for negative mood responses, vigour emerged as consistently the highest among all mood responses across all three groups. The results are discussed considering the unique characteristics of elite and non-elite athletes and the protective role of vigour in mental well-being during adversity. By acknowledging athletes' distinct psychological reactions to circumstances hindering competitive sport engagement, this study contributes to understanding how disruptive health crises could affect athletes’ well-being, potentially informing the development of targeted support programmes for athletes confronting similar challenges.

Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.

Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). HAMD-17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)-logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. The rate of depressive symptom in patients with PBC (n=162) was higher than in healthy controls (n=180) (52.5%vs. 16.1%; p<.001). HAMD-17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r=-0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p<.05). In Lasso-logistic regression analysis, HAMD-17 score, human leukocyte antigen (HLA)-DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR]=1.087, 7.353, 1.075, 1.009, 1.005; p<0.05) were independent risk factors for cirrhosis. Elevated HAMD-17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model. Depressive symptoms were associated with disease severity. Elevated HAMD-17 score was a risk factor for cirrhosis in patients with PBC.

Mortality risk factors for crush syndrome after an earthquake in Türkiye: Do systemic inflammatory parameters play any role?

The aim of our study is to assess the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) on 28-day mortality in patients admitted to the intensive care unit with crush syndrome following the Kahramanmaraş earthquake in Türkiye. A total of 63 adult patients with crush syndrome admitted to the intensive care unit after the earthquake were enrolled in this study. The medical records of the patients were examined using follow-up forms and the hospital data system. The mean age of the patients was 38.9±17.3 years, and the median time under debris was 31.5 hours. The 28-day mortality rate was 27%. In univariate generalized estimating equations (GEE) and other analyses, variables that are significant (or candidate variables) between 28-day mortality groups included age as a biological factor. These variables were included in the multivariate GEE model. The effects of continuous renal replacement therapy (CRRT), serum sodium concentration, Sequential Organ Failure Assessment (SOFA) score, and PLR on mortality were statistically significant. Elevated SOFA scores, the necessity for CRRT, increased serum sodium levels, and decreased PLR values are associated with increased 28-day mortality in patients with crush syndrome after an earthquake.

Caffeic acid ameliorates metabolic dysfunction-associated steatotic liver disease via alleviating oxidative damage and lipid accumulation in hepatocytes through activating Nrf2 via targeting Keap1

Metabolic-associated steatotic liver disease (MASLD), known as non-alcoholic fatty liver disease (NAFLD) in the past, encompasses a range of liver pathological conditions marked by the excessive lipid accumulation. Consumption of coffee is closely associated with the reduced risk of MASLD. Caffeic acid (CA), a key active ingredient in coffee, exhibits notable hepatoprotective properties. This study aims to investigate the improvement of CA on MASLD and the engaged mechanism. Mice underwent a 12-week high-fat diet (HFD) regimen to induce MASLD, and liver pathology was assessed using hematoxylin-eosin (H&E) and oil red O (ORO) staining. Hepatic inflammation was evaluated by F4/80 and Ly6G immunohistochemistry (IHC) and myeloperoxidase (MPO) measurement. Pathways and transcription factors relevant to MASLD were analyzed by using microarray data from patients' livers. Oxidative damage was evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Co-immunoprecipitation (CoIP), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) were used to validate the binding between CA and its target protein. CA significantly alleviated liver damage, steatosis and inflammatory injury, and reduced the elevated NAFLD activity score (NAS) in HFD-fed mice. Clinical data indicate that fatty acid metabolism and ROS generation are pivotal in MASLD progression. CA increased the expression of fibroblast growth factor 21 (FGF21), FGF receptor 1 (FGFR1) and β-Klotho (KLB), and promoted fatty acid consumption. Additionally, CA mitigated oxidative stress injury and activated nuclear factor erythroid 2-related factor-2 (Nrf2). In primary hepatocytes isolated from Nrf2 knockout mice, CA's promotion on FGF21 release and inhibition on oxidative stress and lipotoxicity was disappeared. CA could directly bind to kelch-like ECH-associated protein 1 (Keap1) that is an Nrf2 inhibitor protein. This study suggests that CA alleviates MASLD by reducing hepatic lipid accumulation, lipotoxicity and oxidative damage through activating Nrf2 via binding to Keap1.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

High keratin 15 expression reflects favorable prognosis in early cervical cancer patients.

Keratin 15 (KRT15) exhibits inconsistent prognostic roles in different cancers, and its prognostic value in early cervical cancer patients who receive tumor resection remains unknown. This study aimed to assess the relationship of KRT15 expression with prognosis in these patients. Totally, 147 early cervical cancer patients who received tumor resection were reviewed in this retrospective study. KRT15 was detected in formalin-fixed paraffin-embedded tumor tissue by immunohistochemistry (IHC). KRT15 IHC scores were computed by multiplying the percentage of positively stained cells (scored as 0-4) and corresponding staining intensity (scored as 0-3), ranging from 0 to 12. Elevated KRT15 IHC score was linked with moderate to well differentiation (P = 0.005), tumor size ≤ 4cm (P = 0.017), and International Federation of Gynecology and Obstetrics (FIGO) stage Ia/Ib (P < 0.001). KRT15 IHC score was inversely associated with adjuvant radiotherapy (P = 0.025) and adjuvant chemotherapy (P = 0.016). KRT15 IHC score ≥ 1 was linked with increased disease-free survival (DFS) (P = 0.003) and overall survival (OS) (P = 0.049). Meanwhile, KRT15 IHC score ≥ 1 independently predicted increased DFS (hazard ratio = 0.213, P = 0.017), but not OS (P > 0.05). KRT15 IHC score ≥ 3 and KRT15 IHC score ≥ 6 could not predict DFS or OS (all P > 0.05). By subgroup analyses, KRT15 IHC score ≥ 1 forecasted favorable DFS in patients with age > 45years, human papillomavirus-positive, squamous carcinoma, and tumor size ≤ 4cm (all P < 0.05). KRT15 IHC score ≥ 1 and KRT15 IHC score ≥ 3 predicted ascended DFS in patients without adjuvant radiotherapy or adjuvant chemotherapy (all P < 0.05). High KRT15 expression reflects favorable tumor features and longer survival in early cervical cancer patients who receive tumor resection.

Oral Health-Related Quality of Life among Refugees: A Questionnaire-Based Study.

The issue of oral health problems among refugees, not only during their journey but also once they arrive at their destination, is a current one. This study aimed to evaluate the oral health-related quality of life (OHRQoL) of refugees, with the intention of highlighting a potential need for improved education and easier access to dental care. A questionnaire based on the Oral Health Impact Profile (OHIP-14) was distributed via hyperlink on social media, targeting individuals with a refugee background to collect data on their OHRQoL. A total of 401 participants completed the questionnaire. The median OHIP score for all participants was 8 (IQR 2-17) out of a maximum of 56, with 0 representing the best possible OHRQoL. The median OHIP score was 6 (IQR 2-16) for male and 8 (IQR 2-18) for female participants. A comparison of the OHIP score from this study with reference values from non-refugee populations shows an elevated score and, thus, a lower oral quality of life. The findings of this study indicate a clear need for enhanced access to dental care for refugees, coupled with an educational initiative aimed at fostering an appreciation of the importance of daily dental hygiene.

Identification and characterization of immunogenic cell death-related molecular clusters in rheumatoid arthritis

Background: This study is to analyze the potential mechanisms of immunogenic cell death genes (ICDs) in rheumatoid arthritis (RA) using bioinformatics methods and identify potential biomarkers. Method: We utilized the GSE93777 dataset to systematically evaluate the differential expression and immune characteristics of ICDs in RA patients. Thus, molecular clusters related to ICD, immune cell infiltration, and biological characteristics were explored. Weighted gene co-expression network analysis (WGCNA) was then performed to identify cluster-specific differentially expressed genes. Subsequently, we employed a Support Vector Machine (SVM) machine learning model for prediction analysis, with validation conducted using the external dataset GSE15573. Results: A total of 52 differentially expressed ICDs were identified between healthy individuals and RA patients. Compared to healthy individuals, RA patients exhibited high infiltration of T cells CD4 memory activated, T cells gamma delta, Monocytes, and Neutrophils. The ICD subtypes in RA patients displayed significant heterogeneity in terms of immunity. Specifically, Cluster 2 demonstrated elevated immune scores and relatively high levels of immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that cluster-specific differentially expressed genes in Cluster 2 were closely associated with amino acid and glucose metabolism and degradation, as well as the biosynthesis of N-glycosylation. For the diagnosis of RA, the SVM machine model demonstrated optimal performance with relatively low residual and high area under the curve (AUC=0.998) and was validated using an external validation dataset (GSE15573, AUC=0.700). Analysis of the column chart model indicated that CKS2, NDUFB1, CHCHD1, MAGOH, and MAP7D1 could be used as diagnostic markers for RA diseases. Conclusion: This study systematically elucidates the complex relationship between ICD and RA disease and establishes a promising predictive model to evaluate the risk of ICD subtypes and pathological outcomes in RA patients.

Effect of community-based public health service on health-related quality of life among middle-aged and older adults with chronic diseases in China

BackgroundThe growing prevalence of non-communicable chronic diseases poses a significant public health challenge globally, particularly impacting the well-being of aging populations. This study aims to assess the impact of community-based public health service (PHS) on the health-related quality of life (HRQoL) among middle-aged and older adults with chronic diseases in China.MethodsUtilizing data from the China Health and Retirement Longitudinal Study, we constructed a novel scale based on the 36-Item Short Form Health Survey (SF-36) to measure the HRQoL of middle-aged and older patients with hypertension and/or type-2 diabetes. Multivariate linear regression models with Instrument Variables and Propensity Score Matching techniques were applied to examine the effect of PHS on the HRQoL of identified chronic disease patients.ResultsAmong 8,403 hypertensive and/or diabetic patients, only 10.98% had received PHS. After adjusting for covariates, PHS exhibited a significant association with an elevated overall SF-36 score (β = 3.539, p < 0.001). Similar effects were observed in the physical and mental component summary scores, with increases of 1.982 (p < 0.001) and 5.095 (p < 0.001), respectively. Sensitive analysis affirmed the robustness of these findings. Heterogeneity analysis revealed significant HRQoL improvements among males, females, those aged 70 and older, patients with comorbidities, and urban residents, while the effect was less pronounced in the middle-aged, those without comorbidities, or rural dwellers.ConclusionCommunity-based PHS has exerted a positive impact on both the physiological and psychological aspects of HRQoL among middle-aged and older chronic disease patients, with effects varying among individuals with different characteristics. Our findings advocate for enhancing the delivery and utilization of government-funded PHS, increasing health literacy, and promoting early prevention strategies for chronic diseases. Furthermore, targeted health management initiatives for patients with comorbidities and enhancements in the quality of community healthcare services, particularly in rural areas, are deemed necessary.

Quality of life following pelvic exenteration in neoplasms.

Pelvic exenteration (PE) is an extensive surgical treatment reserved for advanced or recurrent pelvic neoplasms, with potential impacts on patients' quality of life (QoL) poorly referenced in the literature. This study aimed to evaluate QoL outcomes among three types of PE. A cross-sectional study assessed 106 patients divided into anterior PE (APE), posterior PE (PPE), or total PE (TPE) groups. QoL was measured using e short form 36 version 2 (SF-36) and the European Organization for Research and Treatment of Cancer QoL Quality of Life Questionnaire Core 30 (QLQ-C30) QoL questionnaires. Descriptive and inferential analyses compared questionnaire scores. The findings unveiled a balance among the three groups concerning demographic variables and comorbidities, with the exception of a male predominance in the APE and TPE cohorts. Notably, the APE group exhibited elevated scores in overall health (assessed via SF-36) and social functioning and diarrhea domains (assessed via QLQ-C30). Moreover, in terms of the fatigue and nausea/vomiting domains (assessed via QLQ-C30), the APE group demonstrated superior QoL compared to the PPE group. Conversely, the PPE group manifested a notably lower QoL in the constipation domain (assessed via QLQ-C30) compared to the other two groups. Additionally, disease recurrence was significantly associated with diminished QoL across multiple domains. APE patients exhibited better QoL than PPE and TPE groups, with disease recurrence adversely affecting QoL.

Machine-learning and scRNA-Seq-based diagnostic and prognostic models illustrating survival and therapy response of lung adenocarcinoma.

Lung cancer is a major cause accounting for cancer-related mortalities, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Given the high clinical and cellular heterogeneities of LUAD, accurate diagnosis and prognosis are crucial to avoid overdiagnosis and overtreatment. Taking full advantage of scRNA-Seq data to resolve the tumor heterogeneities, we explored the overall landscape of LUAD microenvironment. Utilizing the stage-specific tumor cell markers, we have developed highly accurate diagnostic and prognostic models with elevated sensitivity and specificity. The diagnostic model, developed through random forest algorithms with a thirteen-gene signature, achieved an accuracy of 96.4% and an AUC of 0.993. These metrics were further demonstrated by benchmarking with available models and scoring systems in independent cohorts. Concurrently, the prognostic model, formulated via Cox regression with a six-gene signature, effectively predicted overall survival, with elevated risk scores associated with increased fractions of cancer-associated fibroblasts, and higher likelihood of immune escape and T-cell exclusion. Subsequently, two nomograms were developed to predict survival and drug responses, facilitating their integration into clinical practice. Overall, this study underscores the potential of our models for efficient, rapid, and cost-effective diagnosis and prognosis of LUAD, adaptable to multiple expression profiling platforms and quantification methods.

Synthesis, docking and characterization of some novel 5-(S-alkyl)-1.3.4-thiadiazole-2-carboxamide derivatives as anti-inflammatory and antibacterial agents

Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1HNMR, 13CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics.

Ferroptosis-Related Gene Signatures in Epilepsy: Diagnostic and Immune Insights.

Epilepsy is characterized by a multifaceted aetiology. Ferroptosis has recently been implicated in seizure pathophysiology, although its mechanistic role in epilepsy remains obscure. We examined the roles of ferroptosis-related genes (FRGs) in epilepsy cohorts from the GSE143272 dataset. We investigated the associations between gene expression and the immune response by performing CIBERSORT and MCP-counter analyses. By employing unsupervised consensus clustering and weighted gene coexpression network analysis (WGCNA), we delineated robust gene clusters across cohorts. Single-cell RNA sequencing data from the GSE201048 dataset provided insights into the interactions between pivotal ferroptosis-related genes and immune cells. Additionally, we employed qRT‒PCR technology to measure the levels of these central genes in the tissues of epileptic patients and mice. Our findings revealed seven pivotal genes (TFRC, POR, PTGS2, RELA, PGD, TRIM21, and QSOX1) at the forefront in epilepsy specimens. A diagnostic model harnessing these genes exhibited substantial efficacy (AUC = 0.913). Similarly, the qRT‒PCR analysis of samples from epileptic patients and mouse epileptic brain tissues substantiated these findings. Stratification of 91 patients with epilepsy via WGCNA, based on gene expression, revealed distinct immunological profiles. The scRNA-seq data further indicated increased expression of central genes in macrophages and microglia. Notably, these cells and those with elevated ferroptosis scores were significantly enriched in inflammation-related pathways. These findings support the strong involvement of FRGs in the pathogenesis of epilepsy, particularly neuroinflammation. These central genes hold promise as novel diagnostic biomarkers for epilepsy.

The mediating role of shareholders score in fostering environmental innovation through integrated reporting: insight from Japan

Purpose This study aims to investigate the relationship between integrated reporting, environmental innovation and the mediating effect of shareholder scores within the context of Japan. Design/methodology/approach SEM on panel data are used to study the impact of the role of shareholder scores in mediating the effect of integrated reporting on environmental innovation. This empirical study was based on a sample of 420 companies operating in Japan for the period spanning 2010 and 2022. Findings Drawing upon empirical results, this research uncovers the pivotal role of the shareholder's score as a mediating factor in this relationship. A higher shareholder score signifies a governance structure that values shareholder input and fairness in treatment. Empowered shareholders leverage their influence to advocate for transparent reporting practices that encompass environmental considerations. Consequently, firms with elevated shareholder scores are more inclined toward environmental innovation, aligning their strategies with sustainability imperatives. Originality/value The findings contribute to understanding of how corporate governance mechanisms, particularly shareholder empowerment, interact with reporting practices to drive environmental initiatives, providing valuable implications for sustainable business practices globally.