Health Burden Research Articles

A Global Partnership - The design, implementation and evaluation of a Foundation in Oncology Module- Reducing the global health burden of cancer through human resource and capacity strengthening

A Global Partnership - The design, implementation and evaluation of a Foundation in Oncology Module- Reducing the global health burden of cancer through human resource and capacity strengthening

Trends in the incidence and prevalence of cirrhosis in Manitoba, Canada: A population-based study (2010-2019)

Introduction and objectivesThe burden of chronic liver disease and cirrhosis continues to increase in North America. We sought to estimate the incidence and prevalence of cirrhosis in Manitoba, Canada over time and assess changes in trends between 2010-2019. Material and methodsWe performed a population-based study using Manitoba administrative health care data, and two validated case-finding algorithms. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations, adjusting for age and sex. Changes in estimates were tested using linear trend regression models. ResultsTwo algorithms estimated the number of prevalent cirrhosis to be 16,140 and 29,943 respectively. The age- and sex-adjusted incidence rates increased over the study (from 149 to 264 cases per 100,000 population in 2010, to 177 to 388 cases per 100,000 population in 2019). Cirrhosis incidence increased annually by 2-6 %, with the largest increase (6-8 % 95 % CI 7-9 %, p <0.0001) in those aged 18-44 years. Irrespective of the algorithm used, females consistently exhibited higher cirrhosis incidence and prevalence compared to males over time (P <0.0001). Prevalence demonstrated an upward trend among all age groups over time for both algorithms (P < 0.0001). ConclusionsThis population-based study highlights concerning temporal trends in cirrhosis, characterized by rising annual incidence and prevalence estimates, particularly among young adults and females. These findings underscore the urgent need for comprehensive strategies that encompass prevention, early detection, and the delivery of high-quality healthcare and public health initiatives to effectively tackle this escalating health burden.

Nerve conduction velocity studies in diabetic peripheral neuropathy involving sural nerve—A meta-analysis

ABSTRACT Introduction: Diabetes mellitus (DM) poses a significant health burden globally, impacting millions due to its metabolic disruptions. Among its complications, diabetic peripheral neuropathy (DPN) is a prevalent concern, affecting sensory and motor nerves. While various diagnostic methods exist, discrepancies persist in prevalence estimates of DPN among diabetic populations. Objective: This meta-analysis aimed to assess the prevalence of DPN in individuals with DM, focusing on sural nerve conduction velocity (NCV) measurements. Additionally, the study explored how different evaluation techniques influenced prevalence estimates. Methods: A systematic literature search was conducted following PRISMA guidelines across multiple databases. Studies reporting sural nerve NCV measurements in diabetic patients were included. Data extraction, quality assessment, and statistical analyses were performed to synthesize findings. Results: Twenty-six studies met the inclusion criteria, providing insights into sural nerve NCV among diabetic individuals. Pooled analysis revealed a mean sural nerve NCV of 42.12 m/s (95% CI: 39.87-44.36), indicative of reduced conduction velocity in diabetic populations. Furthermore, sural nerve amplitude was significantly lower in diabetic individuals, with a pooled mean of 4.68 μV (95% CI: 3.11-6.25). Conclusion: Individuals with type 2 DM exhibit impaired sural nerve function, as evidenced by reduced NCV and amplitude measurements. Timely NCV assessment, alongside glycemic monitoring, is crucial for identifying and managing DPN to prevent further complications. Interventions addressing glycemic control, dietary regulation, and lifestyle modifications are recommended to mitigate the progression of neuropathy in diabetic populations.

Navigating the landscape of cervical cancer in India: Epidemiology, prevention, current status, and emerging solutions.

Cervical cancer poses a significant health burden for women worldwide, particularly in India. Despite global progress, India's mortality rate, with 79 906 deaths, remains disproportionately high at approximately 11.2 per 100 000 women compared to the global average of 7.1 per 100 000 women. India's NPCDCS and other initiatives focus on VIA screening for women aged 30-65. The National Health Policy 2017 emphasizes primary healthcare enhancement, allocating two-thirds of the budget. Ayushman Bharat promotes universal health coverage, including Health and Wellness Centers and PM-JAY. Initiatives like Ayushman Bharat and the National Cancer Grid offer hope for improved cancer care. Leveraging technology, strengthening infrastructure, integrating services, promoting awareness, and enhancing HPV vaccination are crucial. By addressing barriers, improving access, and fostering collaboration, the cervical cancer burden can be reduced, ensuring better health outcomes for women nationwide.

Impact of baseline body mass index on antidepressant response: A study in newly diagnosed patients at a tertiary care center in Kolkata

Background: Depression, affecting 350 million globally, poses significant morbidity and mortality. The correlation between major depressive disorder (MDD) and obesity is noted, with studies indicating poorer treatment outcomes among obese individuals. Measuring weight and body mass index (BMI) could aid in predicting depression treatment outcomes, influencing drug efficacy due to their ease of measurement, amid the shared public health burden of MDD and obesity. Aims and Objectives: The aims and objectives of the study are to evaluate baseline BMI’s impact on antidepressant response in newly diagnosed outpatient department (OPD) patients at a tertiary care center. Materials and Methods: This longitudinal observational study was conducted with OPD patients at a tertiary care center, aged 18–65 years with newly diagnosed MDD. Assessment tools included the Diagnostic Criteria for Research accompanying the ICD-10, the Hamilton Rating Scale for Depression, and physical measurement devices. Sample size determination considered BMI groups: Normal to underweight (N1=120), overweight (N2=120), and obese (N3=70). The methodology involved patient history, examination, and follow-up assessments after 6 weeks, analyzing antidepressant response statistically. Results: Obese patients exhibited reduced treatment response rates compared to normal and overweight counterparts. Responders had lower mean BMI. Gender disparities in obesity prevalence were noted. Limitations: The study’s limitations include a small sample size of 310 cases, single-center design, and potential selection bias in a tertiary care setting. Conclusion: The findings underscore the complex relationship between BMI, depression severity, and treatment response. Obese individuals demonstrated higher initial depression scores and poorer treatment response, echoing previous research. The study highlights the need for personalized treatment approaches that consider individual BMI levels to optimize depression management strategies effectively.

The Impact of Iron Deficiency on Prognosis in Stroke and Non-Stroke Populations: A Retrospective Cohort Study

Background and AimsIron deficiency (ID) leads to a significant global health burden, but research on the impact of ID on the prognosis of stroke patients is rare. We aim to investigate the impact of ID on the all-cause mortality of both the stroke and non-stroke individuals. Methods and ResultsThis retrospective cohort study used data from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2002. The follow-up period for the participants extended until December 31, 2019. Overall, 7239 participants were enrolled, out of which 200 had a history of stroke. There was no difference in the prevalence of ID (ferritin <100 ng/mL or serum ferritin concentration 100-299 ng/mL with transferrin saturation (TSAT) <20%) between stroke and non-stroke individuals (68% vs 65%, P =0.5) even after propensity score matching (68% vs 63%, P =0.5). In stroke survivors, ID was found to be associated with a higher risk of all-cause mortality over a 5-year period (HR: 4.16, 95% CI: 1.54-11.3, P = 0.005). Additionally, there was no link between ID and all-cause mortality in individuals without stroke. Moreover, we did not observe a significant association between dietary iron, total folate, and ID in stroke patients. ConclusionStroke survivors with low serum ferritin levels have an increased risk of 5-year all-cause mortality. Health care providers should consider screening for ID among individuals with a history of stroke. Future clinical trials examining the effects of iron therapy on patients with stroke and coexisting ID are warranted.

Machine-Learning Application for Predicting Metabolic Dysfunction-Associated Steatotic Liver Disease Using Laboratory and Body Composition Indicators.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global health burden without established curative therapies. Early detection and preventive strategies are crucial for effective MASLD management. This study aimed to develop and validate machine-learning (ML) algorithms for accurate MASLD screening in a geographically diverse, large-scale population. Data from the prospective Fasa Cohort Study, initiated in rural Fars province, Iran (March 2014), were employed for this purpose. The required data were collected using blood tests, questionnaires, liver ultrasonography, and physical examinations. A two-step approach identified key predictors from over 100 variables: (1) statistical selection using mean decrease Gini in random forest and (2) incorporation of clinical expertise for alignment with known MASLD risk factors. The hold-out validation approach (with a 70/30 train/validation split) was utilized, along with 5-fold cross-validation on the validation set. Logistic regression, Naïve Bayes, support vector machine, and light gradient-boosting machine (LightGBM) algorithms were compared for model construction with the same input variables based on area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. A total of 6,180 adults (52.7% female) were included in the study, categorized into 4816 non-MASLD and 1364 MASLD cases with a mean age (±standard deviation [SD]) of 48.12 (±9.61) and 49.47 (±9.15) years, respectively. Logistic regression outperformed other ML algorithms, achieving an accuracy of 0.88 (95% confidence interval [CI]: 0.86-0.89) and an AUC of 0.92 (95% CI: 0.90-0.93). Among more than 100 variables, the key predictors included waist circumference, body mass index (BMI), hip circumference, wrist circumference, alanine aminotransferase levels, cholesterol, glucose, high-density lipoprotein, and blood pressure. Integration of ML in MASLD management holds significant promise, particularly in resource-limited rural settings. Additionally, the relative importance assigned to each predictor, particularly prominent contributors such as waist circumference and BMI, offers valuable insights into MASLD prevention, diagnosis, and treatment strategies.

Treatment response and clinical features of snakebite envenomation in Alborz province, Iran: A cross-sectional study.

Snakebite envenomation is a significant yet neglected public health burden. Our aim was to investigate the clinical and demographic factors of snakebite envenomation, as well as the factors associated with its severity and response to treatment, in Alborz province, northern Iran. In this cross-sectional study, we included 50 patients diagnosed with snakebite envenomation, referring to the Poison Control Centre of Alborz University of Medical Sciences. The presenting signs and symptoms, demographic data, treatment dose, response to treatment, complications, laboratory findings, and snakebite severity scale (SSS) were collected. Forty-six patients (92%) were men, the total mean age was 31.7 ± 12.06 years, and mean SSS was 6.54 ± 3.39. The patients were admitted for a median of 2 days, and 11 patients needed ICU admissions. The majority of snakebites were in upper extremities (60%) and they mainly occurred in summer (56%). SSS was significantly associated with response to treatment, ICU admission, gastrointestinal adverse events, thrombocytopenia, and length of stay. Similarly, response to treatment was significantly related to the history of snakebite, ICU admission, gastrointestinal adverse events, thrombocytopenia, length of stay, and SSS. Gastrointestinal symptoms, higher severity scores, and longer hospital stays were associated with poor treatment response. Importantly, no mortality was observed in this cohort. Further research is needed to confirm these findings and optimize treatment strategies for snakebite management.

Types, frequencies and burden of health problems in elite luge athletes: a 46-week prospective cohort study

BackgroundThere is a research gap in the survey of injuries and illnesses in the sport of luge.ObjectiveTo analyse the type, frequency and burden of injuries and illnesses that occurred over...

Simvastatin and adenosine-co-loaded nanostructured lipid carriers for wound healing: Development, characterization and cell-based investigation

Chronic wounds represent a significant global health burden, characterized by delayed skin healing and associated comorbidities. The present study aimed to develop nanostructured lipid carriers (NLCs) as a topical delivery system for the co-administration of simvastatin and adenosine to address chronic wound management. The rationale behind the co-delivery approach was to mitigate the cytotoxicity associated with high-dose simvastatin, while preserving its therapeutic benefits through a potential synergistic or additive effect. A significant challenge in the development of these NLCs was the encapsulation of the highly hydrophilic adenosine within the hydrophobic lipid matrix. The NLCs were prepared using a hot homogenization-sonication method with a double emulsion technique and optimized through a series of formulation trials, employing various surfactants, solid and liquid lipids, to achieve efficient drug encapsulation, particularly for the hydrophilic adenosine. Optimized formulations F5- and F10-S/A 0.6 %/2 % (containing 0.6 % simvastatin and 2 % adenosine), exhibited promising physicochemical properties. The main difference was the liquid lipid used: F5 containing Miglyol 810 N, while F10 Capmul MCM C-8. Both formulations displayed a mean particle size below 230 nm, a polydispersity index (PDI) of approximately 0.2, and a zeta potential of around –22 mV. While simvastatin association efficiency (AE) was nearly 100 %, adenosine AE was higher for F10 (24 %), compared to F5 (13.5 %). F5 demonstrated superior stability compared to F10, maintaining consistent particle size and PDI over a 60-day period. Formulation F5 also demonstrated superior cell-based in vitro performance compared to F10, with higher cell viability (MTT assay), greater cell proliferation induction (SRB assay), and enhanced cell proliferation and migration in the wound-scratch assay. While F10 displayed higher adenosine AE, F5 excelled in terms of stability and biological activity. The slightly increase in intracellular reactive oxygen species levels observed with F5 may contribute to its enhanced proliferative effects. In-depth characterization revealed that F5 comprised spherical nanoparticles, and thermal analysis indicated no significant changes in the nanocarrier structure upon drug encapsulation. Additionally, ex vivo permeability study demonstrated superior skin retention of both simvastatin and adenosine for F5 compared to an emulsion control. Overall, the F5 nanocarrier demonstrated suitable physicochemical properties, cellular biocompatibility, induction of cell proliferation and migration events, and drug retention capacity in the skin layers, indicating its potential as a promising topical treatment for difficult-to-heal wounds.

The PrescIT platform: An interoperable Clinical Decision Support System for ePrescription to Prevent Adverse Drug Reactions and Drug-Drug Interactions.

Preventable medication errors have been proven to cause significant public health burden, and ePrescription is a key part of the process where medication errors and adverse effects could be prevented. Information systems and "intelligent" computational approaches could provide a valuable tool to prevent such errors with profound impact in clinical practice. The PrescIT platform is a Clinical Decision Support System (CDSS) that aims to facilitate the prevention of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in the phase of ePrescription in Greece. The proposed platform could be relatively easily localized for use in other contexts too. The PrescIT platform is based on the use of Knowledge Engineering (ΚΕ) approaches, i.e., the use of Ontologies and Knowledge Graphs (KGs) developed upon openly available data sources. Open standards (i.e., RDF, OWL, SPARQL) are used for the development of the platform enabling the integration with already existing IT systems or for standalone use. The main KG is based on the use of DrugBank, MedDRA, SemMedDB and OpenPVSignal. In addition, the Business Process Management Notation (BPMN) has been used to model long-term therapeutic protocols used during the ePrescription process. Finally, the produced software has been pilot tested in three hospitals by 18 clinical professionals via in-person think-aloud sessions. The PrescIT platform has been successfully integrated in a transparent fashion in a proprietary Hospital Information System (HIS), and it has also been used as a standalone application. Furthermore, it has been successfully integrated with the Greek National ePrescription system. During the pilot phase, one psychiatric therapeutic protocol was used as a testbed to collect end-users' feedback. Summarizing the feedback from the end-users, they have generally acknowledged the usefulness of such a system while also identifying some challenges in terms of usability and the overall user experience. The PrescIT platform has been successfully deployed and piloted in real-world environments to evaluate its ability to support safer medication prescriptions.

Hesperitin prevents non-alcoholic steatohepatitis by modulating mitochondrial dynamics and mitophagy via the AMPKα-Drp1/PINK1-Parkin signaling pathway

Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health burden, yet effective therapeutic strategies are notably lacking. NAFLD development may be mediated by mitochondrial dysfunction, according to new research. Producing mitochondrial regulators from plant-based substances to treat mitochondrial dysfunction is an appealing approach to treating NAFLD. Hesperetin (HES) is a flavonoid that is found naturally and is a member of the flavanone family. This study aims to clarify the mechanism of HES in preventing NAFLD which is caused by a high-fat diet (HFD). Serum and liver biochemical parameters, liver histology, lipid profiles, and mitochondrial function were evaluated in HFD-induced NAFLD Sprague-Dawley (SD) rats. HES treatment significantly reduced body weight gain, liver weight, and the liver index, while also improving hepatic steatosis, lipid metabolism disorders, and mitochondrial dysfunction in rats with NAFLD. The mechanism was investigated and confirmed using western blot and real-time quantitative polymerase chain reaction (RT-qPCR). We showed that in the liver of NAFLD rats, HES decreased the expression of dynamic-related protein 1 (Drp1), phosphorylated Drp1 at serine-616 (Drp1-pS616) and induced phosphorylated Drp1 at serine-637 (Drp1-pS637), PTEN-induced kinase 1 (PINK1), and E3 Ubiquitin-Protein Ligase Parkin (Parkin) via an AMP-activated protein kinase alpha (AMPKα)-dependent mechanism. Moreover, HES increased the expression of the mitochondrial fusion proteins mitofusin-2 (Mfn2) and optic atrophy 1 (Opa1) while suppressing the expression of fission protein 1 (Fis1). In this work, we identify a unique mechanism by which HES prevents NAFLD from developing. HES may be an attractive potential therapeutic agent to cure NAFLD.

Molecular correlates of swarming behaviour in Aedes aegypti males.

Mosquitoes are the deadliest vectors of diseases. They impose a huge health burden on human populations spreading parasites as disparate as protozoans (malaria), viruses (yellow fever and more) and nematodes (filariasis) that cause life-threatening conditions. In recent years, mating has been proposed as a putative target for population control. Mosquitoes mate mid-air, in swarms initiated by males and triggered by a combination of internal and external stimuli. As the number of females in a swarm is limited, there is intense competition among males, and they 'retune' their physiology for this demanding behaviour. There is limited knowledge on the 'genetic reprogramming' required to enable swarming. Interestingly, recent evidence indicates that the upregulation of circadian clock genes may be involved in the swarming of malaria mosquitoes of the genus Anopheles. Here, we use whole-head RNA-seq to identify gene expression changes in Aedes aegypti males that are engaged in swarming in a laboratory setting. Our results suggest that in preparation to swarming, males tend to lower some housekeeping functions while increasing remodelling of the cytoskeleton and neuronal connectivity; the transcription of circadian clock genes is unaffected.

Protein Modifications During Early Embryo Development.

Infertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development. Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)-mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein-protein interactions (PPIs) of the modification-related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k-means. We identified modification-related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4-cell stage to the 8-cell stage might be the demarcation period for modification-related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent. The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine-tuned regulatory effects during embryonic development.

Group-Delivered Trauma-Focused CBT Integrating Racial Socialization: A Multiple Case Study

In addition to disparities in interpersonal trauma exposures, Black youth in the U.S. experience the compounding stress of racial trauma, both of which are associated with a disproportionate mental health burden. Black youth also face barriers to engaging with trauma-specific therapies to address trauma-related mental health problems, with research suggesting that they are less likely to complete trauma-specific treatment. Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an evidence-based therapy for trauma-related mental health problems in youth ages 3 to 18. Metzger and colleagues (2021) proposed a set of cultural considerations for Black families to address racial stressors and enhance engagement in TF-CBT. The aim of the current multiple case study was to demonstrate the utility of group-delivered TF-CBT integrating these considerations for a single telehealth group of Black adolescents and their caregivers. We describe the intervention, patient engagement and clinical outcomes, and feedback from families regarding their experience with the group model. We also outline clinical and implementation challenges and highlight directions for future research and clinical practice.

Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.

Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking. A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data. Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02]; P=4.34×10-8). Functional analyses revealed CTNND2 given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such as F2 and FGG were also observed, reinforcing the relevance of our findings. We found CTNND2 as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice.

Identification of Peptidoglycan Glycosyltransferase FtsI as a Potential Drug Target against Salmonella Enteritidis and Salmonella Typhimurium Serovars Through Subtractive Genomics, Molecular Docking and Molecular Dynamics Simulation Approaches.

Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium are among the main causative agents of nontyphoidal Salmonella infections, imposing a significant global health burden. The emergence of antibiotic resistance in these pathogens underscores the need for innovative therapeutic strategies. To identify proteins as potential drug targets against Salmonella Enteritidis and Salmonella Typhimurium serovars using In silico approaches. In this study, a subtractive genomics approach was employed to identify potential drug targets. The whole proteome of Salmonella enteritidis PT4 and Salmonella typhimurium (D23580), containing 393 and 478 proteins, respectively, was analyzed through subtractive genomics to identify human homologous proteins of the pathogen and also the proteins linked to shared metabolic pathways of pathogen and its host. Subsequent analysis revealed 19 common essential proteins shared by both strains. To ensure hostspecificity, we identified 10 non-homologous proteins absent in humans. Among these proteins, peptidoglycan glycosyltransferase FtsI was pivotal, participating in pathogen-specific pathways and making it a promising drug target. Molecular docking highlighted two potential compounds, Balsamenonon A and 3,3',4',7-Tetrahydroxyflavylium, with strong binding affinities with FtsI. A 100 ns molecular dynamics simulation having 10,000 frames substantiated the strong binding affinity and demonstrated the enduring stability of the predicted compounds at the docked site. The findings in this study provide the foundation for drug development strategies against Salmonella infections, which can contribute to the prospective development of natural and cost-effective drugs targeting Salmonella Enteritidis and Salmonella Typhimurium.

Genomics in active surveillance and post-prostatectomy patients: A review of when and how to use effectively.

Prostate cancer (PCa) represents a significant health burden globally, ranking as the most diagnosed cancer among men and a leading cause of cancer-related mortality. Conventional treatment methods such as radiation therapy or radical prostatectomy have significant side effects which often impact quality of life. As our understanding of the natural history and progression of PCa has evolved, so has the evolution of management options. Active surveillance (AS) has become an increasingly favored approach to the management of very low, low, and properly selected favorable intermediate risk PCa. AS permits ongoing observation and postpones intervention until definitive treatment is required. There are, however, challenges with selecting patients for AS, which further emphasizes the need for more precise tools to better risk stratify patients and choose candidates more accurately. Tissue-based biomarkers, such as ProMark, Prolaris, GPS (formerly Oncotype DX), and Decipher, are valuable because they improve the accuracy of patient selection for AS and offer important information on the prognosis and severity of disease. By enabling patients to be categorized according to their risk profiles, these biomarkers help physicians and patients make better informed treatment choices and lower the possibility of overtreatment. Even with their potential, further standardization and validation of these biomarkers is required to guarantee their broad clinical utility. Active surveillance has emerged as a preferred strategy for managing low-risk prostate cancer, and tissue-based biomarkers play a crucial role in refining patient selection and risk stratification. Standardization and validation of these biomarkers are essential to ensure their widespread clinical use and optimize patient outcomes.

Investigation of the causal relationship between cholelithiasis and Parkinson's disease: A bidirectional Mendelian randomization study.

Parkinson's disease (PD) and cholelithiasis are a huge public health burden. Although observational studies have suggested a potential link between PD and cholelithiasis, the causal relationship between the two remains uncertain. To address this gap, we performed a two-sample bidirectional Mendelian randomization analysis using genetic tools. Genome-wide association study summary statistics for all traits were obtained from publicly available databases. We used strict control steps in instrumental variable selection to screen for single nucleotide polymorphisms (SNPs) from summary-level genome-wide association studies. In addition, all F-statistics were >10, indicating no weak instrumental bias. The inverse variance weighting (IVW) method was the primary method used to assess causal associations. Four other MR methods (MR-Egger, Weighted Median, Simple mode, and Weighted mode) were also used to complement IVW. Various sensitivity tests were also performed to assess reliability: (1) Cochrane's Q test for assessing heterogeneity, (2) MR-Egger intercept test and MR-PRESSO global test for assessing horizontal multiplicity, and (3) leave-one-out sensitivity test for determining stability. We selected a total of 30 SNPs as instrumental variables. It was demonstrated that cholelithiasis had a causal effect on the risk of PD (OR = 1.146, 95% CI: 1.062-1.236, p < 0.001) in IVW method. The results of our analysis revealed an increased risk effect of cholelithiasis against PD, which may give light on new approaches to PD prevention and therapy.

Advanced machine learning unveils CD8 + T cell genetic markers enhancing prognosis and immunotherapy efficacy in breast cancer

BackgroundBreast cancer (BC) is the most common cancer in women and poses a significant health burden, especially in China. Despite advances in diagnosis and treatment, patient variability and limited early detection contribute to poor outcomes. This study examines the role of CD8 + T cells in the tumor microenvironment to identify new biomarkers that improve prognosis and guide treatment strategies.MethodsCD8 + T-cell marker genes were identified using single-cell RNA sequencing (scRNA-seq), and a CD8 + T cell-related gene prognostic signature (CTRGPS) was developed using 10 machine-learning algorithms. The model was validated across seven independent public datasets from the GEO database. Clinical features and previously published signatures were also analyzed for comparison. The clinical applications of CTRGPS in biological function, immune microenvironment, and drug selection were explored, and the role of hub genes in BC progression was further investigated.ResultsWe identified 71 CD8 + T cell-related genes and developed the CTRGPS, which demonstrated significant prognostic value, with higher risk scores linked to poorer overall survival (OS). The model’s accuracy and robustness were confirmed through Kaplan-Meier and ROC curve analyses across multiple datasets. CTRGPS outperformed existing prognostic signatures and served as an independent prognostic factor. The role of the hub gene TTK in promoting malignant proliferation and migration of BC cells was validated.ConclusionThe CTRGPS enhances early diagnosis and treatment precision in BC, improving clinical outcomes. TTK, a key gene in the signature, shows promise as a therapeutic target, supporting the CTRGPS’s potential clinical utility.