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Background: The growing number of aging people, ensuring their quality of life (QoL), and the social services designed for this population group are becoming increasingly significant concerns. This study explored how socioeconomic status and self-care affect older adults’ QoL. Methods: This cross-sectional study included 322 older people living in Tabriz in 2021. The subjects were recruited using a multi-stage sampling method. Older persons were asked to complete the Socio-Economic Status (SES) questionnaire, the Self-Care Behavior Questionnaire, and the Iranian version of the 12-item Short Form Health Survey (SF-12). Results: A hierarchical logistic regression analysis model was used to investigate the factors influencing QoL. The regression analysis showed that marital status, social self-care, and self-care during illness significantly impacted the older person’s quality of life (p < 0.05). Twenty-nine and twenty-seven percent of the variance in the mental and physical health dimensions, respectively, were predicted by the variables included in the model.Conclusion: Promoting social self-care and self-care during illness had a positive relationship with the QoL of older persons. These results can serve as a reference for future studies pertinent to self-care for older adults.

Abstract Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.

IntroductionFunctional magnetic resonance imaging (fMRI) has become a fundamental tool for studying brain function. However, the presence of serial correlations in fMRI data complicates data analysis, violates the statistical assumptions of analyses methods, and can lead to incorrect conclusions in fMRI studies.MethodsIn this paper, we show that conventional whitening procedures designed for data with longer repetition times (TRs) (>2 s) are inadequate for the increasing use of short-TR fMRI data. Furthermore, we comprehensively investigate the shortcomings of existing whitening methods and introduce an iterative whitening approach named “IDAR” (Iterative Data-adaptive Autoregressive model) to address these shortcomings. IDAR employs high-order autoregressive (AR) models with flexible and data-driven orders, offering the capability to model complex serial correlation structures in both short-TR and long-TR fMRI datasets.ResultsConventional whitening methods, such as AR(1), ARMA(1,1), and higher-order AR, were effective in reducing serial correlation in long-TR data but were largely ineffective in even reducing serial correlation in short-TR data. In contrast, IDAR significantly outperformed conventional methods in addressing serial correlation, power, and Type-I error for both long-TR and especially short-TR data. However, IDAR could not simultaneously address residual correlations and inflated Type-I error effectively.DiscussionThis study highlights the urgent need to address the problem of serial correlation in short-TR (< 1 s) fMRI data, which are increasingly used in the field. Although IDAR can address this issue for a wide range of applications and datasets, the complexity of short-TR data necessitates continued exploration and innovative approaches. These efforts are essential to simultaneously reduce serial correlations and control Type-I error rates without compromising analytical power.

Abstract Background and aim This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people’s lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates. Method This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated. Results Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period. Conclusion The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.

Abstract Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI). Learning how to uncouple ILICI from ICI anti-tumor activity is of paramount clinical importance. We developed a murine model to recapitulate human ILICI using CTLA4+/- mice treated with either combined anti-CTLA4 + anti-PDL1 or IgG1 + IgG2. We tested two forms of antisense oligonucleotides to knockdown caspase-3 in a total liver (parenchymal and non-parenchymal cells) or in a hepatocyte-specific manner. We also employed imaging mass cytometry (IMC), a powerful multiplex modality for immunophenotyping and cell interaction analysis in our model. ICI-treated mice had significant evidence of liver injury. We detected cleaved caspase-3 (cC3), indicating apoptosis was occurring, as well as Nod-like receptor protein 3 (NLRP3) inflammasome activation, but no necroptosis. Total liver knockdown of caspase-3 worsened liver injury, and induced further inflammasome activation, and Gasdermin-D-mediated pyroptosis. Hepatocyte-specific knockdown of caspase-3 reduced liver injury and NLRP3 inflammasome activation. IMC-generated single-cell data for 77,692 cells was used to identify 22 unique phenotypic clusters. Spatial analysis revealed that cC3+ hepatocytes had significantly closer interactions with macrophages, Kupffer cells, and NLRP3hi myeloid cells than other cell types. We also observed zones of three-way interaction between cC3+ hepatocytes, CD8 + T-cells, and macrophages. Our work is the first to identify hepatocyte apoptosis and NLRP3 inflammasome activation as drivers of ILICI. Furthermore, we report that the interplay between adaptive and innate immune cells is critical to hepatocyte apoptosis and ILICI.

Background: The relationship between inborn errors of immunity (IEIs) and COVID-19 severity and incidence rates remains unclear due to limited and diverse data. This study aimed to address this gap by identifying specific IEIs associated with an increased risk of severe COVID-19 or a predisposition to severe disease before vaccination. Materials and Methods: Data were collected from the medical records of 15 patients with various IEIs, supplemented by interviews with individuals from an IEIs registry who had experienced COVID-19 before vaccination. Results: Among the participants, only three patients (20%) experienced severe-prolonged COVID-19. Notably, this severity was predominantly observed in two male patients with Bruton’s disease (BD) and one female patient with autosomal recessive hypogammaglobinemia. Moderate and severe COVID-19 cases were equally distributed (13.33%). In the female subgroup, one patient with common variable immunodeficiency and another with combined immunodeficiency experienced moderate and severe COVID-19, respectively. Conversely, both male patients with moderate and severe COVID-19 had BD. Conclusion: Despite the limited number of severe cases, the absence of cytokine storm manifestation suggests potential protective mechanisms, possibly due to intravenous immunoglobulin therapy and inherent deficiencies within cytokine-producing cells (B and T cells). While IEIs may not be significant risk factors for COVID-19, they offer promising avenues for further research into therapeutic strategies targeting specific immune system components to mitigate severe COVID-19.

Abstract Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p

Background: Viral hepatitis is one of the world’s top five infectious diseases that cause premature death. Each year, at least one million people die from these infections worldwide. This study investigated the epidemiological features and trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Abadan City, southern Iran.Methods: This cross-sectional study was performed on recorded data of HBV and HCV infections from the notifiable disease surveillance system of Abadan University of Medical Sciences from 2014 to 2020. The incidence per 100,000 population for HBV and HCV infections has been calculated by study years and age groups. The chi-square test was applied to compare various types of infections.Results: The average age of the participants was 40.47±13.20, ranging from 1-88 years. This study estimated the prevalence of HBsAg-positive cases from 2014 to 2020 as 1.53, 6.92, 7.07, 7.07, 8.15, 3.23, and 3.38 per 100,000, respectively. Also, the incidence of HCV-infected cases during these years were 3.23, 6.46, 11.84, 6.46, 8.92, and 2.15 per 100,000 populations, respectively. The average age of patients varied widely based on the type of hepatitis (P=0.001) so that the mean age in HBV-infected patients was 41.06±12.41 years, 41.76±12.99 years in HCV-infected and 22.93±18.02 years in HBV/HCV-infected patients.Conclusion: The findings of this study suggest a lower prevalence of hepatitis B and C compared to other regional studies conducted in Iran. In recent years, the incidence of HBV and HCV has declined, indicating the successful implementation of the vaccination plan and observance of health tips in Abadan.

Objective The purpose of this study was to analyze quantitative values of normal and abnormal marrow on T1-weighted images of spine, to propose a ratio for T1 values of abnormal to normal vertebrae, and to assess whether this ratio could be helpful in predicting presence of neoplastic lesions in the spine.

Coronavirus disease 2019 (COVID-19) is a major threat to world health and safety, making it the primary concern of global community that requires immediate preventive measures. Several organs are affected by this disease simultaneously with possible long-lasting sequelae. Disease pathogenesis is influenced by, the type of virus and its mutation, the number of viruses, individual’s immune system and their age, gender, nutritional status, homeostasis between the immune, nervous and endocrine systems, and also physical condition. All of these factors play a role in the onset, duration, severity, and recurrence of the disease. Since the exact mechanism of infection with this virus is not fully understood, in this study we aimed to investigate its effects on the reproductive system in male and female as well as pregnancy outcome.

Abstract Background Cancers, especially Upper Gastrointestinal Cancers (UGCs), pose a substantial burden on society, particularly in developing nations. Golestan province, Iran, is known for its high UGC rates globally. Aims This study delves into the disease burden of UGCs in the eastern part of Golestan province. Methods and Results This study was conducted using the results of the Golestan cohort study. 2711 patients participating in this cohort, who visited Atrak Clinic during 2001–2020, participated in this study. After excluding patients with incomplete records, 2481 patients were included in the study. To compute the metrics of years of life lost (YLL), years of life lived with disability (YLD), and disability‐adjusted life years (DALY), we utilized the World Health Organization's standard life table, stratified by age and gender. The majority of UGC patients in our study were married (81.8%), had limited formal education (82.6%), and were predominantly male (61.1%). A substantial proportion resided in suburban areas (85.8%), and over half of the patients (52%) reported a history of drug addiction. The mean age at diagnosis for men was 65.76 years with a standard deviation of 11.34, while for women, it was 64.38 years with a standard deviation of 11.66. Regarding disease impact, YLL, YLD, and DALY for men were 21 240, 1956, and 23 196 (307.8 per 100 000), respectively. For women, these figures were 15 609 for YLL, 1367 for YLD, and 16 976 (223.1 per 100 000) for DALY. Conclusion After the increasing trend of the burden of UGCs in Golestan province in the early years of the study, this rate has been decreasing in recent years. Effective strategies necessitate collaborative efforts across various sectors to alleviate this burden, focusing on preventive measures, timely diagnosis, and well‐coordinated therapeutic interventions.

The measurement of productivity change in decision-making units (DMUs) is crucial for assessing their performance and supporting efficient decision-making processes. In this paper, we propose a new approach for measuring productivity change using the Malmquist productivity index (MPI) within the context of two-stage network data envelopment analysis (TSNDEA) under data uncertainty. The two-stage network structure represents a realistic model for DMUs in various fields, such as insurance companies, bank branches, and mutual funds. However, traditional DEA models do not adequately address the issue of data uncertainty, which can significantly impact the accuracy of productivity measurements. To address this limitation, we integrate the MPI methodology with an uncertain programming framework to tackle data uncertainty in the productivity change measurement process. Our proposed approach enables the evaluation of productivity change by capturing both technical efficiency and technological progress over time. By incorporating fuzzy mathematical programming into the DEA framework, we model the inherent uncertainty in input and output data more effectively, enhancing the robustness and reliability of productivity measurements. The utilization of the proposed approach provides decision-makers with a comprehensive analysis of productivity change in DMUs, allowing for better identification of efficiency improvements or potential areas for enhancement. The findings from our study can enhance the decision-making process and facilitate more informed resource allocation strategies in real-world applications.

Background: Coronary Artery Diseases (CAD) are the leading cause of Myocardial Infarction (MI). However, their underlying etiology can be found in the interplay between environmental and genetic factors. On the other hand, it has been shown that Extracellular Matrix (ECM) proteins, such as Thrombospondins (TSP), play a crucial regulatory role in vascular pathologies, including atherogenesis. TSPs are extracellular proteins responsible for intercellular and cell-ECM interactions and are involved in regulating functional responses. Recently, a missense mutation in the TSP-4 gene has been reported to potentially increase the risk of CADs. The present study aimed to investigate the role of rs1866389 Guanosine to Cytosine (G/C) Single Nucleotide Polymorphism (SNP) of the TSP-4 gene on the prevalence of premature MI in southern Iran.Methods: The present case-control study included 100 patients with premature MI and 100 healthy individuals. The DNA extracted from the blood samples of the participants underwent Polymerase Chain Reaction (PCR) for the sequence of the TSP-4 gene. Afterward, the frequency of C (mutated) and G (normal) alleles of the TSP-4 gene was evaluated in the case and control groups. Results: According to our findings, there was no significant intergroup difference in gender, age, and smoking status. However, the case group was significantly higher in the prevalence of Diabetes mellitus (DM), Hyperlipidemia (HLP), and Hypertension (HTN) compared to the control group. Moreover, 22%, 49%, and 29% of the case group had CC, GC, and GG genotypes in the TSP-4 gene, respectively, while the prevalence of CC, GC, and GG genotypes were 10%, 44%, and 46% in the control group. Also, the prevalence of allele C was significantly higher in the case group (47%) compared to the control group (33%, P=0.043), showing its significant association with the increased risk of premature MI (OR = 1.80; 95% CI = 1.01-3.19). Conclusions: The rs1866389 G/C SNP of the TSP-4 gene significantly increased the risk of premature MI in the population of southern Iran. Thus, such mutated gene can be used as a target for gene therapy or a marker for early detection of individuals at high risk for CADs.

Background: Successful treatment of breast cancer (BC) depends on its early detection, which has a significant role in reducing its mortality. The purpose of this study was to evaluate the services provided and the results in women referred to Babol Health Center Breast Cancer Screening Clinic.Methods: This cross-sectional study was performed on 1421 individuals. Data were collected using a questionnaire, including demographic information, health history, and screening questions. Initial examinations were performed by midwives at the centers, and suspected or family history cases were referred to counseling centers and then to a physician for mammography. All follow-up was recorded by an expert in the center.Results: The mean age of the subjects was 46.19±8.84 years, and that at first delivery was 21.08±4.38; 93 (6.5%) of them had a history of infertility and 253 (17.8%) had a family history of BC. Of those who did a clinical examination, mammography and ultrasound, 580 (40.9%), 171 (12%), and 441 (31.1%) had BIRADS above two, respectively, and 12 of those who performed biopsy had a positive mass result. Among the other variables studied, history of benign tumor (OR=2.86, P

Background and purpose: Considering various studies implying anticancer activity of the hydrazone and oxamide derivatives through different mechanisms such as kinases and calpain inhibition, herein, we report the synthesis, characterization, and evaluation of the antiproliferative effect of a series of hydrazones bearing oxamide moiety compounds (7a-7n) against a panel of cancer cell lines to explore a novel and promising anticancer agent (7k). Experimental approach: Chemical structures of the synthesized compounds were confirmed by FTIR, 1H-NMR, 13C-NMR, and mass spectra. The antiproliferative activity and cell cycle progression of the target compound were investigated using the MTT assay and flow cytometry. Findings/Results: Compound 7k with 2-hydroxybenzylidene structure was found to have a significant in vitro anti-proliferative influence on MDA-MB-231 (human adenocarcinoma breast cancer) and 4T1 (mouse mammary tumor) cells as the model of triple-negative breast cancer, with the IC50-72h values of 7.73 ± 1.05 and 1.82 ± 1.14 μM, respectively. Following 72-h incubation with compound 7k, it caused MDA-MB-231 cell death through G1/S cell cycle arrest at high concentrations (12 and 16 μM). Conclusion and implications: Conclusively, this study for the first time reports the anti-proliferative efficacy of compound 7k possessing 2-hydroxyphenyl moiety, which may serve as a potent candidate in triple-negative breast cancer treatment.

Introduction Influenza virus infection is associated with high morbidity and mortality, and so additional therapeutic strategies to reduce the burden for healthcare systems are needed. Statins, by virtue of their anti-inflammatory and immunomodulatory effects, have been hypothesized as capable of influencing the host’s response against the influenza virus. The aim of this meta-analysis was to assess the effect of ongoing statin treatment on susceptibility to influenza virus infection and on influenza-associated mortality. Material and methods Studies investigating the impact of statin treatment on influenza prevalence and mortality were searched for in the PubMed-Medline, Scopus, ISI Web of Knowledge, Embase, Proquest, OVID, EBSCO, and CINAHL databases (up to 8 November 2021). Fixed- and random-effects models and the generic inverse variance method were used for quantitative data synthesis. Results In the meta-analysis of 14 arms of 2 eligible studies, including 14,997 flu-vaccinated and unvaccinated patients, treatment with statins was associated with a reduction of influenza virus prevalence (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.73–0.99; p = 0.040). No significant effect of statins on the susceptibility to influenza infection was observed in the distinct communities of either vaccinated or unvaccinated subjects. Among 9 arms of 6 eligible studies, including 87,204 patients, the use of statins among patients with influenza was associated with a reduced mortality (OR = 0.68, 95% CI: 0.56, 0.82; p < 0.001). This result was confirmed for both 30-day mortality since influenza infection diagnosis (OR = 0.61, 95% CI: 0.47, 0.80; p

Summary: Each human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. We evaluated each multi-omics phenotype’s ability to separately and jointly inform functional rare variation. By combining expression and protein data, we observed rare stop variants 62 times and rare frameshift variants 216 times as frequently as controls, compared to 13–27 times as frequently for expression or protein effects alone. We extended a Bayesian hierarchical model, “Watershed,” to prioritize specific rare variants underlying multi-omics signals across the regulatory cascade. With this approach, we identified rare variants that exhibited large effect sizes on multiple complex traits including height, schizophrenia, and Alzheimer’s disease.

To describe the sonographic appearance of pronator teres syndrome and the role of ultrasound-guided hydrodissection for its management.