Global, regional, and national quality of care index of cervical and ovarian cancer: a systematic analysis for the global burden of disease study 1990-2019.

BACKGROUND AND OBJECTIVE: Cervical cancer is the most preventable and ovarian cancer is the most lethal gynecological cancer. However, in the world, there are disparities in health care performances resulting in differences in the burden of these cancers. The objective of this study was to compare the health-system quality of care and inequities for these cancers using the Quality of Care Index (QCI). MATERIAL AND METHODS: The 1990-2019 data of the Global Burden of Disease (GBD) was analyzed to extract rates of incidence, prevalence, mortality, Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years of healthy life lost due to disability (YLD) of cervical and ovarian cancer. Four indices were developed as a proxy for the quality of care using the above-mentioned rates. Thereafter, a Principal Components Analysis (PCA) was applied to construct the Quality of Care Index (QCI) as a summary measure of the developed indices. RESULTS: The incidence of cervical cancer decreased from 1990 to 2019, whereas the incidence of ovarian cancer increased between these years. However, the mortality rate of both cancers decreased in this interval. The global age-standardized QCI for cervical cancer and ovarian cancer were 43.1 and 48.5 in 1990 and increased to 58.5 and 58.4 in 2019, respectively. QCI for cervical cancer and ovarian cancer generally decreased with aging, and different age groups had inequitable QCIs. Higher-income countries generally had higher QCIs for both cancers, but exceptions were also observed. CONCLUSIONS: Uncovering disparities in cervical and ovarian cancer care across locations, Socio-Demographic Index levels, and age groups necessitate urgent improvements in healthcare systems for equitable care. These findings underscore the need for targeted interventions and prompt future research to explore root causes and effective strategies for narrowing these gaps.

Engineering chimeric autoantibody receptor T cells for targeted B cell depletion in multiple sclerosis model: An in-vitro study.

Background: Recent evidence suggests that B cells and autoantibodies have a substantial role in the pathogenesis of Multiple sclerosis. T cells could be engineered to express chimeric autoantibody receptors (CAARs), which have an epitope of autoantigens in their extracellular domain acting as bait for trapping autoreactive B cells. This study aims to assess the function of designed CAAR T cells against B cell clones reactive to the myelin basic protein (MBP) autoantigen. Methods: T cells were transduced to express a CAAR consisting of MBP as the extracellular domain. experimental autoimmune encephalomyelitis (EAE) was induced by injecting MBP into mice. The cytotoxicity, proliferation, and cytokine production of the MBP-CAAR T cells were investigated in co-culture with B cells. Results: MBP-CAAR T cells showed higher cytotoxic activity against autoreactive B cells in all effector-to-target ratios compared to Mock T cell (empty vector-transduced T cell) and Un-T cells (un-transduced T cell). In co-cultures containing CAAR T cells, there was more proliferation and inflammatory cytokine release as compared to Un-T and Mock T cell groups. Conclusion: Based on these findings, CAAR T cells are promising for curing or modulating autoimmunity and can be served as a new approach for clone-specific B cell depletion therapy in multiple sclerosis.

Prevalence of plasma lipid abnormalities and associated risk factors among Iranian adults based on the findings from STEPs survey 2021.

The study aimed to estimate the prevalence of lipid abnormalities in Iranian adults by demographic characterization, geographical distribution, and associated risk factors using national and sub-national representative samples of the STEPs 2021 survey in Iran. In this population-based household survey, a total of 18,119 individuals aged over 25 years provided blood samples for biochemical analysis. Dyslipidemia was defined by the presence of at least one of the lipid abnormalities of hypertriglyceridemia (≥ 150 mg/dL), hypercholesterolemia (≥ 200 mg/dL), high LDL-C (≥ 130 mg/dL), and low HDL-C (< 50 mg/dL in women, < 40 mg/dL in men), or self-reported use of lipid-lowering medications. Mixed dyslipidemia was characterized as the coexistence of high LDL-C with at least one of the hypertriglyceridemia and low HDL-C. The prevalence of each lipid abnormality was determined by each population strata, and the determinants of abnormal lipid levels were identified using a multiple logistic regression model. The prevalence was 39.7% for hypertriglyceridemia, 21.2% for hypercholesterolemia, 16.4% for high LDL-C, 68.4% for low HDL-C, and 81.0% for dyslipidemia. Hypercholesterolemia and low HDL-C were more prevalent in women, and hypertriglyceridemia was more prevalent in men. The prevalence of dyslipidemia was higher in women (OR = 1.8), obese (OR = 2.8) and overweight (OR = 2.3) persons, those residents in urban areas (OR = 1.1), those with inappropriate physical activity (OR = 1.2), patients with diabetes (OR = 2.7) and hypertension (OR = 1.9), and participants with a history (OR = 1.6) or familial history of CVDs (OR = 1.2). Mixed dyslipidemia prevalence was 13.6% in women and 11.4% in men (P < 0.05). The prevalence of lipid abnormalities was highly heterogeneous among provinces, and East Azarbaijan with 85.3% (81.5-89.1) and Golestan with 68.5% (64.8-72.2) had the highest and lowest prevalence of dyslipidemia, respectively. Although the prevalence of high cholesterol and LDL-C had a descending trend in the 2016-2021 period, the prevalence of dyslipidemia remained unchanged. There are modifiable risk factors associated with dyslipidemia that can be targeted by the primary healthcare system. To modify these risk factors and promote metabolic health in the country, action plans should come to action through a multi-sectoral and collaborative approach.

The burden of metabolic risk factors in North Africa and the Middle East, 1990-2019: findings from the Global Burden of Disease Study.

Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6-35.2) and 23.4% (15.9-31.5) over 1990-2019, respectively, high-BMI with 5.1% (-9.0-25.9) and high-FPG with 21.4% (7.0-37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9-39.0) and 25.2% (16.8-33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (-6.5-28.8) and high-FPG with 27.0% (14.3-40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8-103.3), 76.0% (58.9-99.3), 10.4% (3.8-18.0), and 5.5% (4.3-7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990-2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill & Melinda Gates Foundation.

Assessing the Research Performance of the Iranian Medical Academics and Universities: A Bibliometric Analysis.

Background: Implementing bibliometric indicators is the most prominent way to quantify the current status of research performance. This study aimed to map out the research performance of Iranian medical academics and universities in 2020 and determine its progress from 2016. Methods: Data were extracted from the Iranian scientometric information database and universities' scientometric information database. Then, the data were analyzed to provide descriptive statistics of bibliometric indicators. Besides, the association between the research productivity of academics or universities with their background characteristics was investigated using Mann-Whitney U, Kruskal-Wallis, and chi-square tests. Results: Iranian medical academics had extensive research productivity from 2016 to 2020, leading to 2.5-fold increase in their median number of papers. The research productivity was heterogeneous among the academics, with an H-index ranging from 0 to 98, and a median of 4. The research productivity was different by gender, academic position, general field of study, and academic degree. The class 1 universities had a higher quantity in research performance; however, there was no difference in quality-related indices comprising citations per paper ratio and high impact publication rate (SJR Q1) among different university classes. The median international collaboration rate has followed a growing trend in recent years and was 17% in 2020. Conclusion: There is a remarkable growth in the research productivity of Iranian academics and universities. Iranian research community historically had rare international research collaborations; however, promising growth is shown in this regard. To maintain the growth in research productivity, the country should increase research and development expenditure, address gender disparities, supply universities that are lagging behind, facilitate further international collaboration, and support national journals to be indexed in the international citation databases.

Global, regional, and national quality of care of gallbladder and biliary tract cancer: a systematic analysis for the global burden of disease study 1990-2017.

BACKGROUND: To improve health outcomes to their maximum level, defining indices to measure healthcare quality and accessibility is crucial. In this study, we implemented the novel Quality of Care Index (QCI) to estimate the quality and accessibility of care for patients with gallbladder and biliary tract cancer (GBBTC) in 195 countries, 21 Global Burden of Disease (GBD) regions, Socio-demographic Index (SDI) quintiles, and sex groups. METHOD: This cross-sectional study extracted estimates on GBBTC burden from the GBD 2017, which presents population-based estimates on GBBTC burden for higher than 15-year-old patients from 1990 to 2017. Four secondary indices indicating quality of care were chosen, comprising Mortality to incidence, Disability-Adjusted Life Year (DALY) to prevalence, prevalence to incidence, and years of life lost (YLL) to years lived with disability (YLD) ratios. Then, the whole dataset was analyzed using Principal Component Analysis to combine the four indices and create a single all-inclusive measure named QCI. The QCI was scaled to the 0-100 range, with 100 indicating the best quality of care among countries. Gender Disparity Ratio (GDR) was defined as the female to male QCI ratio to show gender inequity throughout the regions and countries. RESULTS: Global QCI score for GBBTC was 33.5 in 2017, which has increased by 29% since 1990. There was a considerable gender disparity in favor of men (GDR = 0.74) in 2017, showing QCI has moved toward gender inequity since 1990 (GDR = 0.85). Quality of care followed a heterogeneous pattern among regions and countries and was positively correlated with the countries' developmental status reflected in SDI (r = 0.7; CI 95%: 0.61-0.76; P value< 0.001). Accordingly, High-income North America (QCI = 72.4) had the highest QCI; whereas, Eastern Sub-Saharan Africa (QCI = 3) had the lowest QCI among regions. Patients aged 45 to 80 had lower QCI scores than younger and older adults. The highest QCI score was for the older than 95 age group (QCI = 54), and the lowest was for the 50-54 age group (QCI = 26.0). CONCLUSIONS: QCI improved considerably from 1990 to 2017; however, it showed heterogeneous distribution and inequity between sex and age groups. In each regional context, plans from countries with the highest QCI and best gender equity should be disseminated and implemented in order to decrease the overall burden of GBBTC.

Nucleic Acid-Based Treatments Against COVID-19: Potential Efficacy of Aptamers and siRNAs.

Despite significant efforts, there are currently no approved treatments for COVID-19. However, biotechnological approaches appear to be promising in the treatment of the disease. Accordingly, nucleic acid-based treatments including aptamers and siRNAs are candidates that might be effective in COVID-19 treatment. Aptamers can hamper entry and replication stages of the SARS-CoV-2 infection, while siRNAs can cleave the viral genomic and subgenomic RNAs to inhibit the viral life cycle and reduce viral loads. As a conjugated molecule, aptamer-siRNA chimeras have proven to be dual-functioning antiviral therapy, acting both as virus-neutralizing and replication-interfering agents as well as being a siRNA targeted delivery approach. Previous successful applications of these compounds against various stages of the pathogenesis of diseases and viral infections, besides their advantages over other alternatives, might provide sufficient rationale for the application of these nucleic acid-based drugs against the SARS-CoV-2. However, none of them are devoid of limitations. Here, the literature was reviewed to assess the plausibility of using aptamers, siRNAs, and aptamer-siRNA chimeras against the SARS-CoV-2 based on their previously established effectiveness, and discussing challenges lie in applying these molecules.

National and Subnational Cancer Incidence for 22 Cancer Groups, 2000 to 2016: A Study Based on Cancer Registration Data of Iran.

BACKGROUND: Cancer is an increasing public health concern, and detailed knowledge of the cancer incidence is required for developing effective cancer control plans. The objective of this study is to present the cancer incidence of 22 cancer groups in Iran and all 31 provinces of the country from 2000 to 2016, for both sexes across different age groups. METHOD: To study the national and provincial cancer incidence in Iran, we extracted data from the Cancer Project, which collects the Iranian cancer registry data and visualizes it in the VIZIT data visualization system. The methodology and statistical analysis that is used in this study follow the cancer project study protocol. Joinpoint analysis was performed to calculate the average annual percent change of the crude rates and age-standardized rates from 2000 to 2016. RESULTS: Cancer incidence was 126,982 patients in 2016, and the crude rate (CR) of cancer in both sexes and all ages was 155 per 100,000 people. Cancer incidence approximately doubled between 2000 and 2016; however, the age-standardized rate (ASR) had a less drastic increase. The most incident cancers in 2016 were breast, skin, and colorectal cancers; however, the ranking of cancer groups by incidence was different in different age and sex groups and provinces. Some cancers exhibited a unique distribution pattern in the country with high-incidence local areas. Discussion. The study showed that cancer incidence, crude rate, and age-standardized rate (ASR) in Iran had increased in 2000-2016 with vast heterogeneity by cancer type, province, and sex. Moreover, it was shown that the crude rate of cancer in Iran was much less than the global cancer crude rate. Providing such data helps to allocate resources and develop effective national cancer control plans appropriately.

JAK/STAT-Dependent Chimeric Antigen Receptor (CAR) Expression: A Design Benefiting From a Dual AND/OR Gate Aiming to Increase Specificity, Reduce Tumor Escape and Affect Tumor Microenvironment.

Recent advances in cancer immunotherapy have attracted great interest due to the natural capacity of the immune system to fight cancer. This field has been revolutionized by the advent of chimeric antigen receptor (CAR) T cell therapy that is utilizing an antigen recognition domain to redirect patients' T cells to selectively attack cancer cells. CAR T cells are designed with antigen-binding moieties fused to signaling and co-stimulatory intracellular domains. Despite significant success in hematologic malignancies, CAR T cells encounter many obstacles for treating solid tumors due to tumor heterogeneity, treatment-associated toxicities, and immunosuppressive tumor microenvironment. Although the current strategies for enhancing CAR T cell efficacy and specificity are promising, they have their own limitations, making it necessary to develop new genetic engineering strategies. In this article, we have proposed a novel logic gate for recognizing tumor-associated antigens by employing intracellular JAK/STAT signaling pathway to enhance CAR T Cells potency and specificity. Moreover, this new-generation CAR T cell is empowered to secrete bispecific T cell engagers (BiTEs) against cancer-associated fibroblasts (CAFs) to diminish tumor metastasis and angiogenesis and increase T cell infiltration.

MSC-derived exosomes carrying a cocktail of exogenous interfering RNAs an unprecedented therapy in era of COVID-19 outbreak.

BACKGROUND: The onset of the SARS-CoV-2 pandemic has resulted in ever-increasing casualties worldwide, and after 15 months, standard therapeutic regimens are yet to be discovered. MAIN BODY: Due to the regenerative and immunomodulatory function of MSCs, they can serve as a suitable therapeutic option in alleviating major COVID-19 complications like acute respiratory distress syndrome. However, the superior properties of their cognate exosomes as a cell-free product make them preferable in the clinic. Herein, we discuss the current clinical status of these novel therapeutic strategies in COVID-19 treatment. We then delve into the potential of interfering RNAs incorporation as COVID-19 gene therapy and introduce targets involved in SARS-CoV-2 pathogenesis. Further, we present miRNAs and siRNAs candidates with promising results in targeting the mentioned targets. CONCLUSION: Finally, we present a therapeutic platform of mesenchymal stem cell-derived exosomes equipped with exogenous iRNAs, that can be employed as a novel therapeutic modality in COVID-19 management aiming to prevent further viral spread within the lung, hinder the virus life cycle and pathogenesis such as immune suppression, and ultimately, enhance the antiviral immune response.

Improved dynamics of sharing research findings in the COVID-19 epidemic compared with the SARS and Ebola epidemics.

BACKGROUND: When a new or re-emergent pathogen, such as SARS-CoV-2, causes a major outbreak, rapid access to pertinent research findings is crucial for planning strategies and decision making. We researched whether the speed of sharing research results in the COVID-19 epidemic was higher than the SARS and Ebola epidemics. We also researched whether there is any difference in the most frequent topics investigated before and after the COVID-19, SARS, and Ebola epidemics started. METHODS: We used PubMed database search tools to determine the time-period it took for the number of articles to rise after the epidemics started and the most frequent topics assigned to the articles. RESULTS: The main results were, first, the rise in the number of articles occurred 6 weeks after the COVID-19 epidemic started whereas, this rise occurred 4 months after the SARS and 7 months after the Ebola epidemics started. Second, etiology, statistics & numerical data, and epidemiology were the three most frequent topics investigated in the COVID-19 epidemic. However, etiology, microbiology, and genetics in the SARS epidemic, and statistics & numerical data, epidemiology, and prevention & control in the Ebola epidemic were more frequently studied compared with other topics. Third, some topics were studied more frequently after the epidemics started. CONCLUSIONS: The speed of sharing results in the COVID-19 epidemic was much higher than the SARS and Ebola epidemics, and that there is a difference in the most frequent articles' topics investigated in these three epidemics. Due to the value of time in controlling epidemics spread, the study highlights the necessity of defining more solutions for rapidly providing pertinent research findings in fighting against the next public health emergency.

CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer.

The clustered regularly interspaced short palindromic repeats system has demonstrated considerable advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Given that cancer is caused by an excessive accumulation of mutations that lead to the activation of oncogenes and inactivation of tumor suppressor genes, the CRISPR/Cas9 system is a therapy of choice for tumor genome editing and treatment. In defining its superior use, we have reviewed the novel applications of the CRISPR genome editing tool in discovering, sorting, and prioritizing targets for subsequent interventions, and passing different hurdles of cancer treatment such as epigenetic alterations and drug resistance. Moreover, we have reviewed the breakthroughs precipitated by the CRISPR system in the field of cancer immunotherapy, such as identification of immune system-tumor interplay, production of universal Chimeric Antigen Receptor T cells, inhibition of immune checkpoint inhibitors, and Oncolytic Virotherapy. The existing challenges and limitations, as well as the prospects of CRISPR based systems, are also discussed.