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IScience Jun 2024Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis...
Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.
PubMed: 38957790
DOI: 10.1016/j.isci.2024.110111 -
International Journal of Chronic... 2024Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.
METHODS
Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal.
RESULTS
The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.
CONCLUSION
In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pyroptosis; Databases, Genetic; Predictive Value of Tests; Gene Expression Profiling; Lung; Male; Female; Middle Aged; Genetic Markers; Case-Control Studies; Transcriptome; Aged; Reproducibility of Results; Genetic Predisposition to Disease; Prognosis
PubMed: 38957709
DOI: 10.2147/COPD.S438686 -
Ghana Medical Journal Sep 2023To determine if the number of vaso-occlusive events in SCD relates to plasma concentration of fucosyltransferase 7 (FUT7), which catalyses the synthesis of selectin...
OBJECTIVE
To determine if the number of vaso-occlusive events in SCD relates to plasma concentration of fucosyltransferase 7 (FUT7), which catalyses the synthesis of selectin ligands.
DESIGN
A prospective, analytical study.
SETTING
Haematology and Chemical Pathology Departments of tertiary healthcare centres.
PARTICIPANTS
Steady state HbSS individuals aged 13-45 years, 20 had 3 or more vaso-occlusive crises that required hospital admission in the previous year (with or without complications of SCD); 17 other HbSS persons had 0-1 vaso-occlusive crisis that required hospital admission in the previous year and no disease complications.
INTERVENTION
Steady-state plasma concentrations of FUT7 measured by ELISA were compared between SCD patients who had one vaso-occlusive crisis requiring hospital treatment in the previous year but no disease complications and those who had >3 crises with or without complications.
MAIN OUTCOME MEASURES
Plasma level of FUT7and the number of vaso-occlusive events in each HbSS patient.
RESULTS
Mean + standard deviation plasma concentration of FUT7 was 8.6 + 2.7 ng/ml in patients with >3 vasoocclusive crises in the previous year and 7.3 + 1.7 ng/ml in those with 0-1 crisis and no complications; independent sample t-test, p > 0.05, not significantly different.
CONCLUSION
Plasma concentration of fucosyltransferase7 is not associated with the number of vaso-occlusive events in sickle cell disease.
FUNDING
None declared.
Topics: Humans; Fucosyltransferases; Anemia, Sickle Cell; Adult; Female; Male; Prospective Studies; Adolescent; Young Adult; Middle Aged; Vascular Diseases; Enzyme-Linked Immunosorbent Assay; Biomarkers
PubMed: 38957672
DOI: 10.4314/gmj.v57i3.6 -
Journal of Cellular Immunology 2024
PubMed: 38957649
DOI: 10.33696/immunology.6.193 -
Annals of Gastroenterological Surgery Jul 2024Malnutrition, characterized by altered body composition and impaired function, is particularly prevalent among gastric cancer patients, affecting up to 60% of them.... (Review)
Review
Malnutrition, characterized by altered body composition and impaired function, is particularly prevalent among gastric cancer patients, affecting up to 60% of them. Malnutrition in these patients can manifest both before and after surgery, due to factors such as gastric outlet obstruction, cancer cachexia, and anatomical changes. Notably, total gastrectomy (TG) presents the most significant nutritional challenges. However, function-preserving gastrectomy, such as pylorus-preserving gastrectomy (PPG) and proximal gastrectomy (PG), have shown promise in improving nutritional outcomes. Effective nutritional risk screening and assessment are vital for identifying patients at risk. Nutritional support not only improves nutritional parameters but also reduces complications, enhances quality of life (QoL) and survival rates. Those unable to maintain more than 50% of the recommended intake for over 7 days are recommended for nutritional support. Common methods of nutritional support include oral nutrition supplements (ONS), enteral nutrition (EN), or parenteral nutrition (PN) depending on the patient's status. Effect of perioperative nutritional support remains controversial. Preoperative interventions including ONS and PN have shown mixed results, with selective benefits in patients with sarcopenia or hypoalbuminaemia, while impact of EN in gastric outlet obstruction patients have been positive. In contrast postoperative support appears to be consistent. Tube feeding after TG has shown improvements, and ONS have been effective in reducing weight loss and improving nutritional biomarkers. PN was also associated with benefits such as weight maintenance and QoL. This review explores the mechanisms, assessment, and clinical impact of malnutrition, emphasizing the importance of nutritional support in gastric cancer patients undergoing gastrectomy.
PubMed: 38957563
DOI: 10.1002/ags3.12788 -
IEEE Open Journal of Signal Processing 2024The ADReSS-M Signal Processing Grand Challenge was held at the 2023 IEEE International Conference on Acoustics, Speech and Signal Processing, ICASSP 2023. The challenge...
The ADReSS-M Signal Processing Grand Challenge was held at the 2023 IEEE International Conference on Acoustics, Speech and Signal Processing, ICASSP 2023. The challenge targeted difficult automatic prediction problems of great societal and medical relevance, namely, the detection of Alzheimer's Dementia (AD) and the estimation of cognitive test scoress. Participants were invited to create models for the assessment of cognitive function based on spontaneous speech data. Most of these models employed signal processing and machine learning methods. The ADReSS-M challenge was designed to assess the extent to which predictive models built based on speech in one language generalise to another language. The language data compiled and made available for ADReSS-M comprised English, for model training, and Greek, for model testing and validation. To the best of our knowledge no previous shared research task investigated acoustic features of the speech signal or linguistic characteristics in the context of multilingual AD detection. This paper describes the context of the ADReSS-M challenge, its data sets, its predictive tasks, the evaluation methodology we employed, our baseline models and results, and the top five submissions. The paper concludes with a summary discussion of the ADReSS-M results, and our critical assessment of the future outlook in this field.
PubMed: 38957540
DOI: 10.1109/ojsp.2024.3378595 -
Cureus Jul 2024Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to...
BACKGROUND
Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission.
METHODS
This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome.
RESULTS
The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptom onset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982).
CONCLUSION
In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.
PubMed: 38957516
DOI: 10.7759/cureus.63700 -
JGH Open : An Open Access Journal of... Jul 2024The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to... (Review)
Review
The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease - well demonstrated in children - are growing for adults. Novel biomarkers such as interleukin-2 that identify the gluten-specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case-finding strategy and enthusiasm for population screening is growing. The gluten-free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly-responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super-sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.
PubMed: 38957478
DOI: 10.1002/jgh3.13107 -
Frontiers in Immunology 2024Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy...
INTRODUCTION
Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched.
METHODS
In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance.
RESULTS
Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed , , and as potential contributors to primary resistance, with , and emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC.
DISCUSSION
These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Drug Resistance, Neoplasm; Biomarkers, Tumor; Transcriptome; Female; Male; Gene Expression Profiling; Middle Aged; Gene Expression Regulation, Neoplastic; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide
PubMed: 38957470
DOI: 10.3389/fimmu.2024.1338162 -
Frontiers in Immunology 2024Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated...
BACKGROUND
Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated the potential role of Gal-9 as a biomarker in patients with rheumatoid arthritis (RA), especially as an indicator of functional limitations and radiographic joint damage.
METHODS
A total of 146 patients with RA and 52 age- and sex-matched healthy controls were included in this study. Clinical data including disease activity, physical function, and radiographic joint damage were assessed. Functional limitation was defined as the Stanford Health Assessment Questionnaire (HAQ) disability index >1. Subjects with joint erosion >0 or joint space narrowing >0 were considered to have radiographic joint damage. Serum Gal-9 levels were detected by an enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression analysis were used to evaluate the association between Gal-9 and high disease activity and functional limitations, and a prediction model was established to construct predictive nomograms.
RESULTS
Serum levels of Gal-9 were significantly increased in patients with RA compared to those in healthy controls (median 13.1 ng/mL vs. 7.6 ng/mL). Patients with RA who were older (>65 years), had a longer disease duration (>5 years), longer morning stiffness (>60mins), elevated serum erythrocyte sedimentation rate and C-reactive protein, and difficult-to-treat RA had significantly higher Gal-9 levels than those in the corresponding control subgroups (all p <0.05). Patients with RA were divided into two subgroups according to the cut-off value of Gal-9 of 11.6 ng/mL. Patients with RA with Gal-9 >11.6 ng/mL had a significantly higher core clinical disease activity index, HAQ scores, Sharp/van der Heijde modified Sharp scores, as well as a higher percentage of advanced joint damage (all p<0.05) than patients with Gal-9 ≤11.6 ng/mL. Accordingly, patients with RA presenting either functional limitations or radiographic joint damage had significantly higher serum Gal-9 levels than those without (both p <0.05). Furthermore, multivariate logistic regression analysis showed that a serum level of Gal-9 >11.6 ng/mL was an independent risk factor for high disease activity (OR=3.138, 95% CI 1.150-8.567, p=0.026) and presence of functional limitations (OR=2.455, 95% CI 1.017-5.926, p=0.046), respectively.
CONCLUSION
Gal-9 could be considered as a potential indicator in patients with RA, especially with respect to functional limitations and joint damage.
Topics: Humans; Arthritis, Rheumatoid; Galectins; Female; Male; Middle Aged; Biomarkers; Aged; Adult; Severity of Illness Index; Case-Control Studies; Joints
PubMed: 38957462
DOI: 10.3389/fimmu.2024.1419676