Targeting autophagy can synergize the efficacy of immune checkpoint inhibitors against therapeutic resistance: New promising strategy to reinvigorate cancer therapy.

Immune checkpoints are a set of inhibitory and stimulatory molecules/mechanisms that affect the activity of immune cells to maintain the existing balance between pro- and anti-inflammatory signaling pathways and avoid the progression of autoimmune disorders. Tumor cells can employ these checkpoints to evade immune system. The discovery and development of immune checkpoint inhibitors (ICIs) was thereby a milestone in the area of immuno-oncology. ICIs stimulate anti-tumor immune responses primarily by disrupting co-inhibitory signaling mechanisms and accelerate immune-mediated killing of tumor cells. Despite the beneficial effects of ICIs, they sometimes encounter some degrees of therapeutic resistance, and thereby do not effectively act against tumors. Among multiple combination therapies have been introduced to date, targeting autophagy, as a cellular degradative process to remove expired organelles and subcellular constituents, has represented with potential capacities to overcome ICI-related therapy resistance. It has experimentally been illuminated that autophagy induction blocks the immune checkpoint molecules when administered in conjugation with ICIs, suggesting that autophagy activation may restrict therapeutic challenges that ICIs have encountered with. However, the autophagy flux can also provoke the immune escape of tumors, which must be considered. Since the conventional FDA-approved ICIs have designed and developed to target programmed cell death receptor/ligand 1 (PD-1/PD-L1) as well as cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) immune checkpoint molecules, we aim to review the effects of autophagy targeting in combination with anti-PD-1/PD-L1- and anti-CTLA-4-based ICIs on cancer therapeutic resistance and tumor immune evasion.

Effect of genetic profiling on surgical decisions at hereditary colorectal cancer syndromes.

Hereditary colorectal cancer syndromes, such as Lynch syndrome and familial adenomatous polyposis (FAP), present significant clinical challenges due to the heightened cancer risks associated with these genetic conditions. This review explores genetic profiling impact on surgical decisions for hereditary colorectal cancer (HCRC), assessing options, timing, and outcomes. Genotypes of different HCRCs are discussed, revealing a connection between genetic profiles, disease severity, and outcomes. For Lynch syndrome, mutations in the MLH1, MSH2, MSH6, and PMS2 genes guide the choice of surgery. Subtotal colectomy is recommended for patients with mutations in MLH1 and MSH2, while segmental colectomy is preferred for those with MSH6 and PMS2 mutations. In cases of metachronous colon cancer after segmental colectomy, subtotal colectomy with ileorectal anastomosis is advised for all mutations. Surgical strategies for primary rectal cancer include anterior resection or abdominoperineal resection (APR), irrespective of the specific mutation. For rectal cancer occurring after a previous segmental colectomy, proctocolectomy with ileal pouch-anal anastomosis (IPAA) or APR with a permanent ileostomy is recommended. In FAP, surgical decisions are based on genotype-phenotype correlations. The risk of desmoid tumors post-surgery supports a single-stage approach, particularly for certain APC gene variants. Juvenile Polyposis Syndrome (JPS) surgical decisions involve genetic testing, polyp characteristics with attention to vascular lesions in SMAD4 mutation carriers. However, genetic profiling does not directly dictate the specific surgical approach for JPS. In conclusion this review highlights the critical role of personalized surgical plans based on genetic profiles to optimize patient outcomes and reduce cancer risk. Further research is needed to refine these strategies and enhance clinical guidelines.

The Role of Long Noncoding RNAs in Cardiomyocyte Proliferation and Heart Regeneration After Myocardial Infarction: A Systematic Review.

Many studies support the idea that long noncoding RNAs (lncRNAs) are significantly involved in the process of cardiomyocyte (CM) regeneration following a myocardial infarction (MI). This study aimed to systematically review the emerging role of lncRNAs in cardiac regeneration by promoting CM proliferation after MI. Furthermore, the review summarized potential targets and the underlying mechanisms of lncRNAs to induce heart regeneration, suggesting utilizing lncRNAs as innovative therapeutic targets for mitigating MI injuries. We searched the PubMed, Scopus, and Web of Science databases for studies on lncRNAs that play a role in heart regeneration after MI. We used search terms that included MI, lncRNAs, CM, and proliferation. Relevant English articles published until June 11, 2023, were systematically reviewed based on inclusion and exclusion criteria. A total of 361 publications were initially identified, and after applying the inclusion and exclusion criteria, nine articles were included in this systematic review. These studies investigated the role of critical lncRNAs in cardiac regeneration after MI, including five upregulated and four downregulated lncRNAs. Acting as a competitive endogenous RNA is one of the main roles of lncRNAs in regulating genes involved in CM proliferation through binding to target microRNAs. The main molecular processes that greatly increase CM proliferation are those that turn on the Hippo/YAP1, PI3K/Akt, JAK2-STAT3, and E2F1-ECRAR-ERK1/2 signaling pathways. This systematic review highlights the significant role of lncRNAs in heart regeneration after MI and their impact on CM proliferation. The findings suggest that lncRNAs could serve as potential targets for therapeutic interventions aiming to enhance cardiac function.

Multiple fractures due to hungry bone syndrome following parathyroidectomy: a clinical case report and review of literature.

BACKGROUND: Hungry bone syndrome (HBS) is defined as prolonged hypocalcemia caused by a sudden decrease in parathyroid hormone (PTH) levels after parathyroidectomy (PTX). Multiple fractures after PTX due to HBS in an end-stage renal disease (ESRD) patient on chronic hemodialysis (HD) are challenging and rare medical conditions presented in this study. CASE PRESENTATION: A 42-year-old ESRD patient on HD 3 times a week presented to Shariati Hospital, Tehran, Iran, complaining of worsening bone pain and loss of appetite. Laboratory data revealed an intact parathyroid hormone (iPTH) concentration of 2500 pg/mL, an alkaline phosphatase (Alp) level of 4340 IU/L, a phosphorus (P) level of 9 mg/dL, and a calcium (Ca) concentration of 7.2 mg/dL. Sestamibi scintigraphy revealed parathyroid adenoma. The findings suggested tertiary hyperparathyroidism (HPT-III), and the patient was scheduled for total PTX. Approximately one month after surgery, the patient was referred due to convulsions, leg mobility problems, and worsening bone pain. There was bilateral femoral ecchymosis. The Ca concentration was 5.8 mg/dL, and radiological evaluations revealed multiple skeletal fractures. HBS after PTX was suggested for this patient. After several days of hospitalization, he suffered subcutaneous emphysema followed by rib fractures and passed away. CONCLUSIONS: Multiple fractures after PTX due to HBS following HPT-III in ESRD patients are rare and demanding, highlighting the necessity of timely diagnosis and management of patients with HPT-III. Severe hypocalcemia following PTX can cause skeletal disorders. However, the surgical treatment of parathyroid adenomas may be more important than the risk of complications associated with bone health.

Gut microbiota alterations in renal transplant recipients and the risk of urinary tract infection and delayed graft function: A preliminary prospective study.

BACKGROUND: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects. METHODS: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1 week, and 1 month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli, and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA). RESULTS: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p < 0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p = 0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila (p = 0.12), Bacteroid fragilis (p = 0.75), Bifidobacterium (p = 0.99), Escherichia coli (p = 0.5), Faecalibacterium (p = 0.98), and Lactobacilli (p = 0.93) between patients with and without delayed graft function (DGF). CONCLUSION: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF.

The Factor Structure and Generalizability of the Iranian Socioeconomic Status (SES) Questionnaire Administered in a Nationally Divergent Population.

Background: Measuring socioeconomic status (SES) as an independent variable is challenging, especially in epidemiological and social studies. This issue is more critical in large-scale studies on the national level. The present study aimed to extensively evaluate the validity and reliability of the Iranian SES questionnaire. Methods: This psychometric, cross-sectional study was conducted on 3000 households, selected via random cluster sampling from various areas in East Azerbaijan province and Tehran, Iran. Moreover, 250 students from Tabriz University of Medical Sciences were selected as interviewers to collect data from 40 districts in Iran. The construct validity and internal consistency of the SES questionnaire were assessed using exploratory and confirmatory factor analyses and the Cronbach's alpha. Data analysis was performed in SPSS and AMOS. Results: The complete Iranian version of the SES questionnaire consists of 5 factors. The Cronbach's alpha was calculated to be 0.79, 0.94, 0.66, 0.69, and 0.48 for the occupation, self-evaluation of economic capacity, house and furniture, wealth, and health expenditure, respectively. In addition, the confirmatory factor analysis results indicated the data's compatibility with the 5-factor model (comparative fit index = 0.96; goodness of fit index = 0.95; incremental fit index = 0.96; root mean square error of approximation = 0.05). Conclusion: According to the results, the confirmed validity and reliability of the tool indicated that the Iranian version of the SES questionnaire could be utilized with the same structure on an extensive level and could be applicable for measuring the SES in a broader range of populations.

What is the link between the dietary inflammatory index and the gut microbiome? A systematic review.

PURPOSE: One highlighted pathogenesis mechanism of diseases is the negative impact of pro-inflammatory diets (PD) on the gut microbiome. This systematic review aimed to study the link between dietary inflammatory index (DII), as an indicator of PD, and gut microbiome. METHODS: A systematic search was done in PubMed and Scopus, adhering to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The assessment of the included studies' quality was performed using the critical appraisal checklist from the Joanna Briggs Institute. RESULTS: Ten articles were included eight cross-sectional, one case-control, and, one cohort study. Seven and three included articles reported a weak and moderate relationship between gut microbiome and DII scores, respectively. DII scores were linked to variety in microbiome composition and diversity/richness. More importantly, anti-inflammatory diets as measured by lower DII scores were linked to a more desirable gut microbiome profile. Prevotella stercorea, Veillonella rogosae, Morganella morganii, Ruminococcus torques, Eubacterium nodatum, Alistipes intestine, Clostridium leptum, Morganellaceae family, Enterobacteriaceae family, and, Bacteroides thetaiotaomicron were related to higher DII scores. While, Butyrate-producing bacteria such as Ruminococcaceae and Lachnospiraceae families, Faecalibacterium prausnitzii, and Akkermansia muciniphila were related to lower DII scores. CONCLUSION: An anti-inflammatory diet, as measured by a lower DII score, might be linked to variations in the composition and variety of the microbiome. Therefore, the DII score could be useful in microbiota research, however, this possibility needs to be investigated more precisely in future studies.

Thirty-three-year follow-up of pseudoaneurysm of the mitral-aortic intervalvular fibrosa without surgical treatment: a case report and literature review.

BACKGROUND: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (PMAIF) is a rare complication of infective endocarditis or aortic valve surgery. Surgical treatment is suggested, but the long-term follow-up of conservative management remains unclear. CASE PRESENTATION: A 33-year follow-up of a patient who developed PMAIF six years after aortic valve replacement is reported. The patient presented to our center with dyspnea, and the echocardiography revealed an ejection fraction of 20% and a PMAIF measuring 7 × 10 mm. Despite being advised to undergo surgery, the patient declined due to fear of surgical outcomes. Consequently, conservative treatment with close observation but without surgery was initiated. During the 33-year follow-up period, the patient did not experience any adverse health effects. CONCLUSION: Surgical intervention should be considered whenever the PMAIF is diagnosed. However, in any case that the surgery was not applicable, conservative management might lead to long-term survival, based on this and similar case reports in the literature.

Quality of Life and Socioeconomic Status in Northwest of Iran: First Wave of the Persian Traffic Cohort Study.

This study aimed to evaluate the association between Quality of Life (QOL) and independent factors, emphasizing Socio Economic Status (SES) in northwestern Iran. A population-based cross-sectional study was performed within the Persian Traffic safety and health Cohort in 2020. Participants were chosen using stratified random sampling method. The majority of participants (69%) were aged between 30 and 65. Around half of the participants were males (54.44%). Most of the female respondents were categorized as very low and medium levels of SES Based on multiple linear regression analysis, the QOL among females was lower compared to males (ß: - 0.92, 95% CI - 1.82 to - 0.22). There was a negative association between SES and QOL; individuals with low and very low levels of SES had a lower QOL than those with a medium level of SES (ß: - 4.38, 95% CI - 5.9 to - 2.86) (ß: - 2.65, 95% CI - 4.08 to - 1.22). The current study highlights that higher SES and educational levels are positively associated with higher QOL. Conversely, older age, females, and widowed individuals are linked with lower QOL.

Lymphedema after saphenous harvesting for coronary artery bypass surgery: case report and literature review.

Different causes have been described for secondary lymphedema as reported in this article. A 75-year-old man was diagnosed with lymphedema about one decade after saphenous harvesting for coronary artery bypass surgery. It took two years for him to find out his diagnosis and receive the proper treatment. After standard complete decongestive therapy, his volume and pain decreased and his quality of life was improved, especially its physical aspect. It is important to recognize the possibility of lymphedema development after saphenous harvesting among patients undergoing coronary artery bypass surgery to prevent significant disturbance of quality of life with timely management.

Massive cardiac vegetation and cardiomyopathy in a 23-year-old rancher with brucellosis.

Key clinical massage: A 23-year-old rancher was admitted with the diagnosis of brucellosis. In evaluations, a massive vegetation in the aortic valve was seen. A combination of antibiotic therapy and cardiac surgery were performed, it seems this approach reduces mortality and complications. Abstract: Brucellosis (also known as "undulant fever," "Mediterranean fever," or "Malta fever") is a zoonotic infection transmitted to humans from infected animals (cattle, sheep, goats, camels, pigs, or other animals) by ingestion of food products (such as unpasteurized dairy products) or by contact with tissue or fluids. It is the most frequent zoonosis globally and a major public health issue in many resource-poor nations. Endocarditis is one of the rarest and most dangerous consequences of brucellosis. Additionally, the combination of endocarditis with cardiomyopathy increases its rarity. This condition is usually treated with a high level of suspicion Serological, clinical, and epidemiological data can all be used to make a diagnosis. The use of echocardiography aids in the early diagnosis. Due to the high risk of recurrence and the extent of tissue destruction brought on by Brucella, the majority of experts advise an early surgical intervention; nevertheless, other writers assert that low-risk patients also require cautious therapy. In this article, we discuss the situation of a patient who underwent surgery and had Brucella endocarditis and heart failure. In conclusion, a combination of antibiotic therapy and cardiac surgery, reduces mortality and complications associated with Brucella endocarditis and improves patient quality of life.

miRNAs and exosomal miRNAs in lung cancer: New emerging players in tumor progression and therapy response.

Non-coding RNAs have shown key roles in cancer and among them, short RNA molecules are known as microRNAs (miRNAs). These molecules have length less than 25 nucleotides and suppress translation and expression. The functional miRNAs are produced in cytoplasm. Lung cancer is a devastating disease that its mortality and morbidity have undergone an increase in recent years. Aggressive behavior leads to undesirable prognosis and tumors demonstrate abnormal proliferation and invasion. In the present review, miRNA functions in lung cancer is described. miRNAs reduce/increase proliferation and metastasis. They modulate cell death and proliferation. Overexpression of oncogenic miRNAs facilitates drug resistance and radio-resistance in lung cancer. Tumor microenvironment components including macrophages and cancer-associated fibroblasts demonstrate interactions with miRNAs in lung cancer. Other factors such as HIF-1α, lncRNAs and circRNAs modulate miRNA expression. miRNAs have also value in the diagnosis of lung cancer. Understanding such interactions can pave the way for developing novel therapeutics in near future for lung cancer patients.

Exploring the Causal Impact of Age and Nighttime Driving on Road Traffic Injuries among Elderly Drivers: A Bayesian LASSO Approach.

Objective: To determine the causal relationship between aging and nighttime driving and the odds of injury among elderly drivers. Methods: In this cross-sectional study, 5460 car accidents were investigated from 2015 to 2016. The data were extracted from the Iranian Integrated Road Traffic Injury Registry System. Pedestrian accidents, motorcycle crashes, and fatalities were excluded from the study. To account for major confounders, Bayesian-LASSO, and treatment-effect cutting-edge approaches were used. Results: Overall, 801 injuries (14.67%) were evaluated. The results of the univariable analysis indicated that aging and nighttime had adverse effects on the odds of road traffic injuries (RTIs), even after adjusting for the effect of other variables, these effects remained statistically significant. According to a newly developed approach, the overall effects of aging and nighttime were significantly and directly correlated with the odds of being injured for older adults (both p<0.001). Our findings indicated that drivers over 75 years old experienced 23% higher injury odds (OR=1.23, 95% CI:1.11 to 1.39; p<0.001), while driving at night increased the odds by 1.78 times (OR=1.78, 95% CI:1.51 to 1.83; p<0.001). Conclusion: Aging and nighttime driving are significant risk factors for RTIs among elderly drivers. This highlights the importance of implementing targeted interventions to enhance road safety for this vulnerable population. Furthermore, the use of advanced Bayesian-LASSO and treatment-effect statistical methods highlights the importance of utilizing sophisticated methodologies in epidemiological research to effectively capture and adjust for potential confounding factors.

Barriers to the sustainable adoption of autonomous vehicles in developing countries: A multi-criteria decision-making approach.

The acceptance of AI-based intelligent transportation systems requires addressing the existing barriers and the adoption of macro-decisions and policies by policymakers and governments. This study evaluates the potential barriers to the adoption of Autonomous Vehicles (AVs) in developing countries by considering the sustainability dimensions. The barriers are identified by conducting a comprehensive literature review and studying the academic experts' opinions in related industries. By identifying the main barriers to the sustainable adoption of AVs, a synthesized approach of the Rough Best-Worst Method (RBWM) and Interval-Rough Multi-Attributive Border Approximation Area Comparison (IR-MABAC) is utilized for weighting and evaluating each barrier in this context. According to the results of this study, the "inflation rate", "lack of internet connection quality", and "learning challenges and difficulties to use the AVs" are the top challenges and barriers to the AV adoption which need to be considered by policymakers. As the main contribution of this research, we provide efficient insights on a macro policy scale for decision-makers with respect to the main barriers to the implementation of AVs technology. From the AVs literature and to the best of our knowledge, this is the first study of its kind that considers the barriers to the AV technology implementation through the sustainability concept.

Validity and reliability of short-form travel behavior questionnaire during COVID-19 pandemic (TBQ-Cov19).

Introduction: Avoiding unnecessary travel and reducing the number of essential travels are among the effective strategies for preventing the spread of COVID-19 during the pandemic. Given that it is impossible to avoid essential travel, health protocols should be observed to prevent disease transmission. The extent to which health protocols are observed during the trip should be accurately assessed by a valid questionnaire. Therefore, this study aims to develop and validate a questionnaire to assess compliance with COVID-19 prevention protocols during travel. Methods: In this cross-sectional study, 285 individuals were selected from six provinces using the cluster sampling method in May and June 2021. The Content Validity Ratio (CVR) and Content Validity Index (CVI) were calculated using the comments of 12 external experts. The exploratory factor analysis (EFA), with principal component factor in the extraction method and Varimax rotation, were applied to determine construct validity. Cronbach's alpha was employed to assess internal consistency and the Spearman-Brown correlation coefficient was computed for test-retest reliability. Results: In the content validity phase, the I-CVIs for all items were acceptable, but due to a low CVR value (below 0.56), one question was eliminated. As a result of EFA for construct validity, two factors were extracted that justified 61.8% of the variance. Cronbach's alpha coefficient of the questionnaire, with 10 items, was 0.83. The Spearman-Brown correlation coefficient was 0.911 which confirmed the stability of the questionnaire at an excellent level. Conclusions: This questionnaire is a valid tool with good validity and reliability for assessing compliance with health protocols in travel during the COVID-19 pandemic.

Road safety lead agency challenges of three decades of intervention for road safety in Iran: implications for policy-makers.

BACKGROUND: Road traffic crashes and associated injuries and mortalities are one of the big public health challenges, especially in low/middle-income countries. Road safety lead agency (RSLA) is a vital factor in the sustainable prevention and promotes road safety. In the recent decades, various policy interventions have been conducted for road safety in Iran. This study aimed at exploring the challenges of RSLA from the perspectives of stakeholders at various levels. METHODS: A qualitative study was conducted. In-depth interviews and document reviews were used for data collection. To conduct interviews, different stakeholders at various levels such as policy-makers, senior national authorities, researchers and faculty members were selected. Data collection was conducted between November 2019 and June 2020. Thematic content analysis approach was used for data analysis. RESULTS: The experts' perspectives were analysed and then categorised under five main themes including the role and position of the lead agency, the role and duties of the actors and players, translating policy into practice, intrasectoral and intersectoral cooperation and coordination and evidence production and application and a total of 22 subthemes were identified. The current structure of the RSLA is one of the main challenges emphasised by the research participants. CONCLUSION: To achieve significant improvements in road safety at the national level, a strong management system and leadership body is a critical issue. Organisational reform to establish an effective unique lead agency is proposed to cope with RSLA challenges.

Effect of music on driving performance and physiological and psychological indicators: A systematic review and meta-analysis study.

Background: Many studies have assessed the effect of music on driving. However, their results are very scattered and contradictory. Therefore, this systematic review is conducted to determine the effect of music on driving performance and drivers' physiological and psychological indicators. Methods: Scopus, PubMed, and Web of Science databases were searched until July 2023. A manual search in Google Scholar for gray literature was conducted. The Simulation Research Rubric (SRR) tool was used to assess the reporting quality of the studies. Stata software (StataCorp, version 16) was used to perform a meta-analysis. Results: A total of 2650 records were identified. The findings of 19 studies were analyzed. Most of them were carried out in high-income countries (HICs) using simulators. The most frequently used music style was classic rock. The meta-analysis results indicated that music with high and medium volume increases the average driving speed, and music with low volume decreases it. Although music in every mood reduces the average reaction time, it positively reduces response delay and increases coherence. Music with high volume decreases the heart rate, but music with medium and low volume increases it. Listening to music increases the level of arousal and mental load. Conclusion: It was concluded that, in some indicators, listening to music has adverse effects on driving. However, in many indicators, music has a positive impact on improving driving safety. It is better to choose appropriate music for different driving conditions and to train the drivers about it.

Updates in immunocompatibility of biomaterials: applications for regenerative medicine.

INTRODUCTION: Biomaterials, either metallic, ceramic, or polymeric, can be used in medicine as a part of the implants, dialysis membranes, bone scaffolds, or components of artificial organs. Polymeric biomaterials cover a vast range of biomedical applications. The biocompatibility and immunocompatibility of polymeric materials are of fundamental importance for their possible therapeutic uses, as the immune system can intervene in the materials' performance. Therefore, based on application, different routes can be utilized for immunoregulation. AREAS COVERED: As different biomaterials can be modulated by different strategies, this study aims to summarize and evaluate the available methods for the immunocompatibility enhancement of more common polymeric biomaterials based on their nature. Different strategies such as surface modification, physical characterization, and drug incorporation are investigated for the immunomodulation of nanoparticles, hydrogels, sponges, and nanofibers. EXPERT OPINION: Recently, strategies for triggering appropriate immune responses by functional biomaterials have been highlighted. As most strategies correspond to the physical and surface properties of biomaterials, specific modulation can be conducted for each biomaterial system. Besides, different applications require different modulations of the immune system. In the future, the selection of novel materials and immune regulators can play a role in tuning the immune system for regenerative medicine.

Setting research priorities to achieve long-term national road safety goals in Iran.

Background: Road traffic crashes (RTCs) and its associated injuries are one of the most important public health problems in the world. In Iran, RTCs rank second in terms of mortality. To address this issue, there is a need for research-based interventions. Prioritizing researches using a variety of approaches and frameworks to determine the most effective interventions is a key nodal point in the RTCs' research policy planning cycle. Thus, this study aims to generate and prioritize research questions in the field of RTCs in Iran. Methods: By adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 25 prominent Iranian academic leaders having role in setting Iran's long-term road safety goals, a group of research funders, and policymakers. The experts' proposed research questions were independently scored on a set of criteria: feasibility, impact on health, impact on the economy, capacity building, and equity. Following the prioritization of Research Questions (RQs), they were all classified using the 5 Pillar frameworks. Results: In total, 145 Research Questions were systematically scored by experts against five criteria. Iran's top 20 road traffic safety priorities were established. The RQs related to "road safety management" and "road and infrastructure" achieved a high frequency. Conclusions: The top 20 research questions in the area of RTCs in Iran were determined by experts. The majority of these RQs were related to "road safety management". The results of this study may contribute to the optimal use of resources in achieving long-term goals in the prevention and control of road traffic crashes and its related injuries. Considering these RQs as research investment options will improve the current status of Road Traffic Injuries (RTIs) at a national level and further advance toward compliance with international goals. If these research priorities are addressed, and their findings are implemented, we can anticipate a significant reduction in the number of crashes, injuries, and deaths.