TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers.

Alterations in the expression of certain genes could be associated with both patient mortality rates and drug resistance. This study aimed to identify genes in colorectal cancer (CRC) that potentially serve as hub genes influencing patient survival rates. RNA-Seq data were downloaded from the cancer genome atlas database, and differential expression analysis was performed between tumors and healthy controls. Through the utilization of univariate and multivariate Cox regression analyses, in combination with the MCODE clustering module, the genes whose expression changes were related to survival rate and the hub genes related to them were identified. The mortality risk model was computed using the hub genes. CRC samples and the RT-qPCR method were utilized to confirm the outcomes. PharmacoGx data were employed to link the expression of potential genes to medication resistance and sensitivity. The results revealed the discovery of seven hub genes, which emerged as independent prognostic markers. These included HOXC6, HOXC13, HOXC8, and TBX15, which were associated with poor prognosis and overexpression, as well as SDHB, COX5A, and UQCRC1, linked to favorable prognosis and downregulation. Applying the risk model developed with the mentioned genes revealed a markedly higher incidence of deceased patients in the high-risk group compared to the low-risk group. RT-qPCR results indicated a decrease in SDHB expression and an elevation in TBX15 levels in cancer samples relative to adjacent healthy tissue. Also, PharmacoGx data indicated that the expression level of SDHB was correlated with drug sensitivity to Crizotinib and Dovitinib. Our findings highlight the potential association between alterations in the expression of genes such as HOXC6, HOXC13, HOXC8, TBX15, SDHB, COX5A, and UQCRC1 and increased mortality rates in CRC patients. As revealed by the PPI network, these genes exhibited the most connections with other genes linked to survival.

The 15-year national trends of urinary cancers incidence among Iranian men and women; 2005-2020.

BACKGROUND: Urinary tract cancers including bladder, kidney, ureter, and pelvis are a common malignancy worldwide with high mortality ratio. Aimed to investigate the prevalence of these cancers, we conducted this study. METHODS: In this study, all the information related to ICD10 codes, gender, age and province of residence of individuals were obtained from the data of Iran's cancer registry by the Ministry of Health, Medicine and Medical Education and demographic evidence for each sub-country from the reports of Statistics Center of Iran (SCI). Also, the data of two Iranian national survey studies CASPIAN-III, IV, and V (information related to the care and prevention of non-communicable diseases (NCD) in childhood and adolescence) and STEPs (including information on NCD in adults over 18 years old) were used. The data was analyzed using Poisson regression with mixed effects to estimate the incidence of cancers. RESULTS: Bladder and kidney neoplasm are the most common cancers of the urinary system in Iran. The prevalence of bladder cancer has increased from 5.82 to 11.50 per 100,000 individuals. The increasing trend is growing faster in men compared with women. The incidence of kidney neoplasm has increased over the years (2.03 in 2005 vs. 7.02 in 2020 per 100,000). Having a higher incidence ratio compared with bladder cancer, kidney cancer is responsible for 35.06% of all urinary cancers in 2020 compared with 23.71% in 2005. Both neoplasms of the ureter and renal pelvis were recorded rarely and with lower incidence in both sexes during this period. CONCLUSION: Considering the increasing trend in the incidence of urinary neoplasms in Iran during these years, the advantage of focusing on the risk of urinary cancers is highlighted. Therefore, investigating the prevalence and incidence of urinary cancers to plan and manage these cancers will result in prevention and reduction of the disease burden on the Iranian society. Future studies in this field can help in the prevention and well-timed diagnosis of these cancers.

Examining the Completeness of Breast Cancer Pathology Reports Registered in the Population-Based Cancer Registration System in Iran during 2016 to 2018.

Background: Ensuring the comprehensive and accurate representation of data within cancer registries holds paramount significance across various facets of public health decision-making. This study delves into the evaluation of data completeness in breast cancer (BC) pathology reports within a population-based cancer registration system in Iran, spanning the period from 2016 to 2018. Methods: Employing a retrospective and descriptive analytical approach, we harnessed secondary data extracted from pathology reports encompassing breast cancer diagnoses, which were duly recorded in the Integrated Cancer Information Management System database during 2016-2018. A total of 4000 pathology reports were thoughtfully selected from each of the three years. The spectrum of pathology information encompassed tumor type, site grade, size (T), and involvement of lymph nodes (N). Summary statistics were provided as percentages of categorical variables and mean with standard deviation of continuous variables. A comparison of categorical variables was performed using the Chi-squared test. Results: The participants' mean age was 51.8±12.5 years. Among the 12,000 studied patients, 5744 (47.9%) were ≤ 50 years old, 5233 (43.6%) were aged 50-69 years, and 1023 (8.5%) were >60 years old. The completeness of BC pathology reports varied for different variables. Interestingly, the completeness of these variables increased with older age groups. The proportion of specific tumor types differed significantly among age groups (P = 0.001). Notably, the prevalence of invasive ductal carcinoma was higher in the ≤ 50 years age group compared to the older cohorts. Likewise, notable variations in tumor sizes were observed (P = 0.009), with a higher prevalence of missing tumor size data noted in the age group ≤ 50 years. On the other hand, pathologic T stage also demonstrated age-dependent variations (P = 0.014), indicating a higher prevalence of missing stages in the ≤ 50 years age group. Finally, tumor grade exhibited a statistically significant difference (P < 0.001), with a higher proportion of grade 1 tumors observed in the 50-69 years age group. Conclusion: Tumor grade had the highest completeness rate, while tumor size, pathologic T stage, and pathologic N stage had the lowest. Therefore, a good understanding of completeness of pathology reports, as well as improvement in the registration of stage, integrated system at the national level for BC is warranted.

Population attributable proportion and number of cancer cases attributed to potentially modifiable risk factors in Iran in 2020.

In the current study, we aimed to calculate the fraction of cancer attributable to modifiable risk factors in Iran in 2020. Population attributable fractions (PAFs) were calculated for established cancer risk factors using three data sources: the national cancer incidence reports, relative risks extracted from global and national meta-analyses, and exposure prevalence from national/subnational population-based surveys. In addition to overall cancers, the PAFs were estimated separately for each cancer site among men and women. Overall, 32.6% of cancers in 2020 in Iran were attributable to known risk factors. The PAF in men (40.2%) was twice as high as in women (21.1%). Cigarette smoking (15.4%), being overweight (5.0%), opium use (3.9%) and H. pylori infection (3.8%) were the leading causes of cancers. For men, the highest PAFs belonged to cigarette smoking (26.3%), opium use (6.8%) and being overweight (3.1%), while for women, the highest PAFs belonged to being overweight (7.2%), H. pylori infection (2.7%) and cigarette smoking (2.7%). Among Iranian men and women, the PAFs of waterpipe smoking were 2% and 0.9%, respectively. A third of incident cancers in Iran are due to modifiable exposures, mainly cigarette smoking, being overweight, and H. pylori infection. Opium consumption and waterpipe smoking collectively accounted for 8.8% of cancer occurrence in men and 1.3% in women in Iran. These emerging risk factors should be taken into consideration in future PAF studies.

The 15-year national trends of genital cancer incidence among Iranian men and women; 2005-2020.

BACKGROUND: Cancer is a major health problem and cause of mortality worldwide. Despite the prevalence of other cancers in males and females, genital cancers are especially important because of their psychological effects on individuals. Currently, cervical cancer, corpus uteri neoplasm, and ovarian cancer are the most common gynecological cancers in Iran. Prostate cancer has increased in Iranian men in the last decade. Therefore, this study aimed to investigate the 15-year national trend in the incidence of genital cancers in the Iranian population. METHODS: In this study, we used Iranian cancer registration data collected by the Ministry of Health and Medical Education, demographic information from the reports of the Statistics Center of Iran, STEPs (STEPwise approach to non-communicable diseases risk factor surveillance), and Caspian (childhood and adolescence surveillance and prevention of adult non-communicable disease). A list of potential auxiliary variables and secondary variables at all levels of the province-age-sex were evaluated during the years. We used mixed-effects Poisson regression to model the data and calculate the incidence of each cancer. RESULTS: Our results show an enhancement in the outbreak of all types of male cancers, but the most important are prostate (11.46 in 2005 to 25.67 in 2020 per 100,000 males) and testicular cancers (2.39 in 2005 to 5.05 per 100,000 males). As for female cancers, there has been an increase in ovarian and corpus uteri neoplasm incidence with 6.69 and 4.14 incidences per 100,000 females in 2020, making them the most occurring female genital neoplasms. While the occurrence of cervical cancer has decreased over the years (4.65 in 2005 to 3.24 in 2020). In general, the incidence of genital cancers in men and women has amplified in the last 15 years. CONCLUSIONS: Our study examined the trend of change for each malignant genital neoplasm for 15 years in Iranian men and women in each province. Considering the growing trend of the elderly population in Iran, patient awareness and early screening are essential in reducing mortality and costs imposed on patients and the health care system.

Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy.

BACKGROUND: Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance. METHODS: Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR. RESULTS: Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs. CONCLUSIONS: Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC.

Physicochemical and sensory properties of malt beverage containing sugar beet saponins.

Aqueous two-phase system (ATPS) composed of polyethylene glycol (PEG) and K2HPO4 solutions was used to extract saponin from sugar beet root. Extraction yield, purity and foam capacity of saponin were optimized according to response surface methodology (RSM). Analysis of liquid chromatography-mass spectrometry (LC-MS) showed that purified saponins were composed of hederagenin, akebonoic acid and oleanolic acid. Addition of 0.02 g sugar beet root saponin to one liter of malt beverage caused a considerable increase in foam volume and stability compared to malt beverage samples containing 0.1 g/L propylene glycol alginate (PGA). Malt beverages containing saponin showed higher turbidity, bitterness and overall sensory acceptance. Moreover, no significant changes in malt drink pH and °Brix were observed due to saponin addition. Adding lemon flavor caused a decrease in foam stability and sensory acceptance of malt beverage containing saponin compared to PGA containing ones. Less saponin content is suggested for flavored malt drinks. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05517-x.

Colorectal Cancer Screening Program Results in Iran.

Background: Colorectal cancer (CRC) accounts for a large proportion of the global burden of cancer and is the fourth leading cause of cancer-related mortality worldwide. Fecal Immunochemical Testing (FIT) can be used for CRC screening programs due to its high accuracy and compliance. The present study reports the preliminary results of the CRC screening program in Iran among all people aged 50 to 69 years. Methods: This cross-sectional study was carried out on 2,669,625 participants referred to health centers in Iran for CRC screening programs in 2018 and 2019. The data required for this study was taken from the CRC screening program. Relevant information for all individuals aged 50 to 69 referred to the health system that was called for colorectal cancer screening was extracted from the Integrated Electronic Health Records (SIB) database. Finally, the standards indices were calculated for all provinces. Gender, history of inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis), history of colon cancer or adenoma in a first-degree family (father, mother, siblings or children), history of colon cancer in a second-degree family if occurred under the age of fifty (aunt, uncle, grandparents), lower gastrointestinal bleeding in a prior month, constipation in the prior month (with or without diarrhea, abdominal pain and feeling of fullness in the colon after defecation), more than ten percent weight loss in the last six months and FIT were assessed. Results: Among a total number of over 2.6 million, 56.3% were female, and the number of people evaluated by health care providers for CRC screening programs in 2018 and 2019 were 1,365,248 (14.23%) and 1,304,377 (12.89%), respectively. The number of people with positive FIT evaluated for the CRC screening program in 2018 and 2019 was 33,299 (3.09%) and 33,583 (2.57%), respectively. Bushehr province (0.59%) and Isfahan province (7.35%) had the lowest and highest positive FIT rate in 2018, respectively. Also, the correlation between the above-mentioned variables and the number of people with a positive FIT across gender was statistically significant (p<0.05). The study of the relationship between the number of positive FIT cases and the variables examined by Behvarz and community health worker showed that the number of people with a family history of colon cancer in second-degree relatives under the age of 50 and also the number of people with an individual history of inflammatory bowel disease had a significant association with the number of positive FIT cases (p<0.05) (ß=-0.718, 95% CI; -2.557-14.992, ß=0.388, 95% CI; 0.322-16.737, respectively). The relationship between the number of positive FIT cases and effective variables was not statistically significant (p>0.05). Conclusion: Positive cases should be referred for further evaluation and colonoscopy. Before performing a screening program, the conditions for performing colonoscopy for these people must be assessed and prepared. The FIT for CRC screening program can be easily promoted in Iran.

Primary Health Care Model for Non-Communicable Diseases Management during COVID-19 Pandemic in the Islamic Republic of Iran.

Background: Given the importance of appropriate response to prevent and manage Non-Communicable Diseases (NCDs), this study aimed to analyze the state of NCDs services at the level of the PHC system during the COVID-19 pandemic and to determine the main strategies. Methods: In this qualitative study, first, the circulars and guides in Iran's PHC system from the beginning of the pandemic to the end of September 2020 were retrieved manually and by searching the internal websites of the Ministry of Health. All documents about decision-making or governance and coordination mechanisms for the provision of NCDs services were enrolled and analyzed. In the second phase, the status of service delivery for major NCDs was presented in a model, and finally, SWOT analysis was used to analyze the situation and determine the main strategies. Results: 25 out of 199 circulars and guides were eligible and analyzed. In the crisis phase, most risk assessment, screening, and diagnosis services for NCDs have been suspended, and follow-up and care of patients with major NCDs were done by telephone. In the reopening phase, the general strategies and strategies to increase capacity and provide delayed care were adopted, and the PHC model of the provision of essential services for the major NCDs was developed in low-risk, intermediate and high-risk pandemic conditions. Finally, 16 main strategies were determined with the approach of integrating and focusing on essential services, considering vulnerable groups and the use of E-health technologies. Conclusion: The results indicate on interruption of NCDs services in the crisis phase while adopting strategies for responding to the pandemic. Revision of the COVID-19 guides with a particular focus on NCDs is recommended.

IRAN National Cancer Control Program (IrNCCP): Goals, Strategies, and Programs.

Background: Annually, over 131000 new cases of cancer have been identified in Iran, with an increasing trend that is predicted to grow by 40% by 2025. The most important contributing factors to this increase are the improvement of the health service delivery system, increased life expectancy, and the aging of the population. The aim of this study was to develop Iran's "National Cancer Control Program" (IrNCCP). Methods: The present study is a cross-sectional study that was conducted in 2013 using the method of reviewing studies and documents and focused group discussions and a panel of experts. In this study, the available evidence related to cancer status and its care in Iran and other countries, as well as national and international upstream documents, were reviewed and analyzed. Then, by analyzing the current situation in Iran and other countries and conducting stakeholder analysis with the strategic planning approach, the IrNCCP was developed with a 12-year horizon consisting of goals, strategies, programs, and performance indicators. Results: This program has 4 main components, including Prevention, Early Detection, Diagnosis and Treatment, and Supportive and Palliative care, as well as 7 supporting components including Governance and policy-making, Cancer Research, Developing facilities, equipment, and service delivery network, Providing and managing human resources, Providing and managing financial resources, Cancer information system management and registry, and Participation of NGOs, charities, and the private sector. Conclusion: Iran's National Cancer Control Program has been developed comprehensively with cross-sectoral cooperation and stakeholder participation. However, like any long-term health intervention, strengthening its governance structure both in terms of implementation and achievement of expected goals and evaluation and modification during the implementation of the program is essential.

Cancer in Iran 2008 to 2025: Recent incidence trends and short-term predictions of the future burden.

Policymakers require estimates of the future number of cancer patients in order to allocate finite resources to cancer prevention, treatment and palliative care. We examine recent cancer incidence trends in Iran and present predicted incidence rates and new cases for the entire country for the year 2025. We developed a method for approximating population-based incidence from the pathology-based data series available nationally for the years 2008 to 2013, and augmented this with data from the Iranian National Population-based Cancer Registry (INPCR) for the years 2014 to 2016. We fitted time-linear age-period models to the recent incidence trends to quantify the future cancer incidence burden to the year 2025, delineating the contribution of changes due to risk and those due to demographic change. The number of new cancer cases is predicted to increase in Iran from 112 000 recorded cases in 2016 to an estimated 160 000 in 2025, a 42.6% increase, of which 13.9% and 28.7% were attributed to changes in risk and population structure, respectively. In terms of specific cancers, the greatest increases in cases are predicted for thyroid (113.8%), prostate (66.7%), female breast (63.0%) and colorectal cancer (54.1%). Breast, colorectal and stomach cancers were the most common cancers in Iran in 2016 and are predicted to remain the leading cancers nationally in 2025. The increasing trends in incidence of most common cancers in Iran reinforce the need for the tailored design and implementation of effective national cancer control programs across the country.

Population or family history based BRCA gene tests of breast cancer? A systematic review of economic evaluations.

BACKGROUND: Nearly 56% of at-risk carriers are not identified and missed as a result of the current family-history (FH) screening for genetic testing. The present study aims to review the economic evaluation studies on BRCA genetic testing strategies for screening and early detection of breast cancer. METHODS: This systematic literature review is conducted within the Cochrane Library, PubMed, Scopus, Web of Science, ProQuest, and EMBASE databases. In this paper, the relevant published economic evaluation studies are identified by following the standard Cochrane Collaboration methods and adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement reporting some recommendations for articles up to March 2020. Thereafter, the inclusion and exclusion criteria are applied to screen the articles. Disagreements are resolved through a consensus meeting. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist is used in the evaluation of quality. Finally, a narrative synthesis is performed. To compare the different levels of incremental cost-effectiveness ratio (ICER), the net present value is calculated based on a discount rate of 3% in 2019. RESULTS: Among 788 initially retrieved citations, 12 studies were included. More than 60% of the studies were originated from high-income countries and were published after 2016. It is noteworthy that most of the studies evaluated the payer perspective. Moreover, the robustness of the results were analyzed through one-way and probabilistic sensitivity analyses in nearly 66% of these studies. Nearly, 25% of the studies are focused and defined population-based and family history BRCA tests as comparators; afterwards, the cost-effectiveness of the former was confirmed. The highest and lowest absolute values for the ICERs were $65,661 and $9 per quality adjusted life years, respectively. All studies met over 70% of the CHEERs criteria checklist, which was considered as 93% of high quality on average as well. CONCLUSIONS: The genetic BRCA tests for the general population as well as unselected breast cancer patients were cost-effective in high and upper-middle income countries and those with prevalence of gene mutation while population-based genetic tests for low-middle income countries are depended on the price of the tests.

Determination of effective factors on geographic distribution of the incidence of colorectal cancer in Tehran using geographically weighted Poisson regression model.

Background: This study aimed to determine effective factors on geographic distribution of the Incidence of Colorectal Cancer (CRC) in Tehran, Iran using Geographically Weighted Poisson Regression Model. Methods: This ecological study was carried out at neighborhood level of Tehran in 2017-2018. Data for CRC incidence was extracted from the population-based cancer registry data of Iran. The socioeconomic variables, risk factors and health costs were extracted from the Urban HEART Study in Tehran. Geographically weighted Poisson regression model was used for determination of the association between these variables with CRC incidence. GWR 4, Stata 14 and ArcGIS 10.3 software systems were used for statistical analysis. Results: The total number of incident CRC cases were 2815 in Tehran from 2008 to 2011, of whom, 2491 cases were successfully geocoded to the neighborhood. The median IRR for local variables were : unemployed people over 15 year old (median IRR: 1.17), women aged 17 years or older with university education (median IRR: 1.17), women head of household (median IRR: 1.06), people without insurance coverage (median IRR: 1.10), households without daily consumption of milk (median IRR: 0.85), smoking households (median IRR: 1.07), household's health expenditure (median IRR: 1.39), disease diagnosis costs (median IRR: 1.03), medicines costs of households (median IRR: 1.05), cost of the hospital (median IRR: 1.09), cost of medical visits (median IRR: 1.27). Conclusion: The spatial variability was observed for most socioeconomic variables, risk factors and health costs that had effects on CRC incidence in Tehran. Spatial variability is necessary when interpreting the results and utterly helpful for implementation of prevention programs.

Assessment of a Hospital Palliative Care Unit (HPCU) for Cancer Patients; A Conceptual Framework.

INTRODUCTION: The first hospital palliative care unit (HPCU) in Iran (FARS-HPCU) has been established in 2008 in the Cancer Institute, which is the largest referral cancer center in the country. We attempted to assess the performance of the HPCU based on a comprehensive conceptual framework. The main aim of this study was to develop a conceptual framework for assessment of the HPCU performances through designing a value chain in line with the goals and the main processes (core and support). MATERIALS AND METHODS: We collected data from a variety of sources, including international guidelines, international best practices, and expert opinions in the country and compared them with national policies and priorities. We also took into consideration the trend of the HPCU development in the Cancer Institute of Iran. Through benchmarking the gap area with the performance standards, some recommendations for better outcome are proposed. RESULTS: The framework for performance assessment consisted of 154 process indicators (PIs), based on which the main stakeholders of the HPCU (including staff, patients, and families) offered their scoring. The outcome revealed the state of the processes as well as the gaps. CONCLUSION: Despite a significant improvement in many processes and indicators, more development in the comprehensive and integrative aspects of FARS-HPCU performance is required. Consideration of all supportive and palliative requirements of the patients through interdisciplinary and collaborative approaches is recommended.

Discovering therapeutic possibilities for polycystic ovary syndrome by targeting XIST and its associated ceRNA network through the analysis of transcriptome data.

Long non-coding RNA (lncRNA) regulates many physiological processes by acting as competitive endogenous RNA (ceRNA). The dysregulation of lncRNA X-inactive specific transcript (XIST) has been shown in various human disorders. However, its role in the pathogenesis of polycystic ovary syndrome (PCOS) is yet to be explored. This study aimed to explore the underlying mechanism of XIST in the pathogenesis of PCOS, specifically through dataset functional analysis. GEO PCOS datasets including RNA-seq, microarray, and miRNA-seq in granulosa cells (GCs) and blood, were examined and comprehensively analyzed. Enrichment analysis, ROC curve constructions, lncRNA-miRNA-mRNA interaction network analyses, and qRT-PCR validation were performed followed by a series of drug signature screenings. Our results revealed significant dysregulation in the expression of 1131 mRNAs, 30 miRNAs, and XIST in GCs of PCOS patients compared to healthy individuals. Of the120 XIST-correlated upregulated genes, 25 were enriched in inflammation-related pathways. Additionally, 5 miRNAs were identified as negative regulators of XIST-correlated genes. Accordingly, a ceRNA network containing XIST-miRNAs-mRNAs interactions was constructed. Furthermore, 6 genes, including AQP9, ETS2, PLAU, PLEK, SOCS3, and TNFRSF1B served as both GCs and blood-based biomarkers. By analyzing the number of interactions among XIST, miRNAs, and mRNAs, we pinpointed ETS2 as the pivotal gene within the ceRNA network. Our findings reveal a novel XIST- hsa-miR-146a-5p, hsa-miR-144-3p, and hsa-miR-1271-5p-ETS2 axis that comprehensively elucidates the XIST-associated mechanism underlying PCOS onset. qRT-PCR analysis further confirmed the, overexpression of both XIST and ETS2 . Furthermore, our results demonstrated that XIST and ETS2 were correlated with some assisted reproductive technologies outcomes. Finally, we identified two novel compounds including, methotrexate/folate and threonine using drug-gene interaction databases for PCOS management. These findings provide novel insights into the molecular etiology, diagnosis, and potential therapeutic interventions for PCOS.

Comparison of the effects of high-intensity interval and moderate-intensity continuous training on inflammatory markers, cardiorespiratory fitness, and quality of life in breast cancer patients.

BACKGROUND: As the effectiveness of breast cancer treatment has improved, a growing number of long-term breast cancer survivors are seeking help for unique health problems. These patients may be at increased risk of cardiovascular disease due to the side effects of treatment. The positive impact of most types of exercise has been repeatedly reported in people with cancer, but the most effective exercise approaches for maximum beneficial adaptations remain controversial. Thus, this study aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on inflammatory indices, adipokines, metabolic markers, body composition, cardiorespiratory fitness, and quality of life in breast cancer patients during adjuvant endocrine therapy. METHODS: Thirty non-metastatic breast cancer patients during adjuvant endocrine therapy who had been treated with chemotherapy and/or radiotherapy were recruited from Iran and randomized to HIIT, MICT, or control groups for a supervised exercise intervention that took place 3 times a week for 12 weeks. The training intensity was determined based on the peak oxygen uptake (VO2peak), and the volume of training was matched in HIIT and MICT based on the VO2peak. Body composition, functional capacity, cardiorespiratory fitness, metabolic indices, sex hormones, adipokines, and inflammatory markers were assessed before and after the intervention. RESULTS: The VO2peak increased by 16.8% in the HIIT group in comparison to baseline values (mean difference = 3.61 mL/kg/min). HIIT significantly improved the VO2peak compared to control (mean difference = 3.609 mL/kg/min) and MICT (mean differences = 2.974 mL/kg/min) groups. Both HIIT (mean difference = 9.172 mg/dL) and MICT (mean difference = 7.879 mg/dL) interventions significantly increased high-density lipoprotein cholesterol levels compared to the control group. The analysis of covariance showed that physical well-being significantly improved in MICT compared to control group (mean difference = 3.268). HIIT significantly improved the social well-being compared to the control group (mean difference = 4.412). Emotional well-being subscale was significantly improved in both MICT (mean difference = 4.248) and HIIT (mean difference = 4.412) compared to the control group. Functional well-being scores significantly increased in HIIT group compared with control group (mean difference = 3.35) . Significant increase were also observed in total functional assessment of cancer therapy-General scores in both HIIT (mean difference = 14.204) and MICT groups (mean difference = 10.036) compared with control group. The serum level of suppressor of cytokine signaling 3 increased significantly (mean difference = 0.09 pg/mL) in the HIIT group compared to the baseline. There were no significant differences between groups for body weight, body mass index, fasting blood glucose, insulin resistance, sex hormone binding globulin, total cholesterol, low-density lipoprotein cholesterol, adipokines, interleukin-6, tumor necrosis factor-α, or interleukin-10. CONCLUSION: HIIT can be used as a safe, feasible, and time-efficient intervention to improve cardiovascular fitness in breast cancer patients. Both HIIT and MICT modalities enhance quality of life. Further large-scale studies will help determine whether these promising results translate into improved clinical and oncological outcomes.

Policy analysis of cervical cancer prevention in Iran based on the policy triangle model.

BACKGROUND: Widespread use of screening in high-income countries has led to a significant reduction in cervical cancer mortality. Most low- and middle-income countries still have poorly organized screening programs. This study aimed at policy analysis of prevention and early detection of cervical cancer in Iran, a middle-income country. MATERIALS AND METHOD: This qualitative retrospective study, extended by the health policy triangle model, was conducted from July 2020 to September 2021. A sample of this study consisted of 43 participants, including 16 key policy experts; nine 11 senior health system managers, 13 executives, and 3 clients selected purposefully. Data were collected through semi-structured interviews using the interview guide and analyzed using a framework analysis method based on the policy triangle model in MAXQDA2020. RESULTS: Nine themes, 15 subthemes, and 36 codes were extracted based on the 4 dimensions of the model; stakeholder analysis challenges, including conflict of interest and decision-making challenges. Moreover, the most important policy process challenges indicated the weakness of monitoring and evaluation systems and weakness of using scientific principles in policy making. Weakness of organizational and intersectoral structure and weakness of executive management were obtained among the challenges in the context analysis. Finally, the most important challenges related to content analysis are weaknesses in applying scientific principles in policy making, including weaknesses in standard operating procedures, and low use of HTA capacity in developed guidelines. CONCLUSION: A wide range of economic, social, and cultural problems can affect cervical cancer prevention policies. Several strategies are suggested to overcome these challenges, including allocating separate funds to cancer prevention programs, using structures to sustain prevention programs, designing, and using them to improve public awareness.

Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery.

OBJECTIVE: Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recent studies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesis of this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-protein interaction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatment of varicocele. MATERIALS AND METHODS: In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 rats were screened using the edgeR package in R software and the results were compared to 3 rats in the control group. Data was obtained from GSE139447. Setting a -11 and P<0.05 as cutoff points for statistical significance, up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networks were drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs were identified from the drug database. RESULTS: Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats with varicocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulated genes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated with the cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findings suggested that dexamethasone may be a promising therapeutic option for individuals with varicocele. CONCLUSION: The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated while the ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could be considered a future candidate drug for the treatment of individuals with varicocele.

Colorectal Cancer Screening Pilot Project in Tehran-Iran, a Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no organised CRC-screening programme. This study aimed to evaluate feasibility of CRC screening using a qualitative fecal immunochemical test (FIT) among Iranian average-risk adults. METHODS: In this feasibility study, 7039 individuals aged 50-75 years were invited by community health workers (CHWs) in southern Tehran and its suburban districts between April 2018 and November 2019. The CHWs performed a qualitative FIT with cut-off level 50 ng Hb/mL buffer and referred those with positive-FIT for colonoscopy to the endoscopy center of Shariati hospital in Tehran. Outcomes included acceptance rate, FIT positivity rate, colonoscopy compliance, detection rates and positive predictive values (PPVs) with 95% confidence interval for CRC and advanced adenomas (AAs). RESULTS: Acceptance rate at initial invitation was 71.7%. From 4974 average-risk adults (1600 males and 3374 females) who were offered FIT, 96.8% (n=4813) provided valid samples, of whom 471 (9.8%) tested positive. Among FIT-positive participants, 150 (31.8%) underwent colonoscopy; CRC was detected in 2.0% (n=3) and adenomas in 27.3% (n=41). Detection rate of CRC and AAs per 1000-FIT-screened participants was 0.6 (0.1-1.8) [males: 0.7 (0.01-3.6), females: 0.6 (0.07-2.0)] and 4.2 (2.5-6.4) [males: 5.9 (2.6-11.0), females: 3.4 (1.7-6.0)], respectively. PPVs were 2.0% (0.4-5.7) for CRC and 13.3% (8.3-19.8) for AAs. There was no association between gender and the studied outcomes. CONCLUSION: Our results partially support the feasibility of scaling up organized CRC-screening through the existing healthcare system in Iran; it remains to be discussed carefully to ensure the capacity of healthcare system for adequate colonoscopy services.