Epidemiological Approach Research Articles

Note on dose conversion for radon exposure

The epidemiological approach to converting radon exposure to effective dose is examined. Based on the definition of the effective dose, the dose conversion is obtained from the equivalence of lung-specific detriment associated with low-LET radiation and with radon exposure. This approach most reliably estimates effective dose per radon exposure on the basis of epidemiological data and implicitly includes the radiation weighting factor required to calculate the effective dose from radon exposure using the dosimetric approach, applying biokinetic and dosimetric models. Consistency between the results of the epidemiological and dosimetric approaches is achieved by using a radiation weighting factor of about 10 for alpha particles instead of the current ICRP value of 20. In contrast, the epidemiological approach implemented in ICRP 65, and referred to as dose conversion convention, was based on direct comparison of total radiation detriment with lung detriment from radon exposure. With the revision of radiation detriments in ICRP 103, this approach can be judged to overestimate the effective dose per radon exposure by about a factor of two because the tissue weighting factor for lung differs from the value of relative detriment to which it relates.

Breast cancer cultural representations: a scoping review.

This article aims to map the global scientific production on social or cultural representations and breast cancer in Public Health and discuss how it is presented in the literature. We conducted a scoping review guided by the question: "How are cultural or social representations in the context of breast cancer described in the global scientific Public Health production?". We searched for works in five scientific literature sources and included 45 studies. The analytical process followed the content analysis technique in the thematic modality. The analyzed collection can be thematized into the following categories: (1) Compromised body image and interactions, (2) Spirituality, (3) Loss of control over life, (4) Going on with life, and (5) Association with ethnic-racial issues. Despite advances in biomedicine, we observed that representations of breast cancer still have metaphors associated with cancer in the last century. We conclude that, among other aspects, care for women with breast cancer cannot be guided only by biomedical and epidemiological approaches since this disease is traversed by knowledge that competes with these approaches.

Representações culturais do câncer de mama: uma revisão de escopo

Abstract This article aims to map the global scientific production on social or cultural representations and breast cancer in Public Health and discuss how it is presented in the literature. We conducted a scoping review guided by the question: “How are cultural or social representations in the context of breast cancer described in the global scientific Public Health production?”. We searched for works in five scientific literature sources and included 45 studies. The analytical process followed the content analysis technique in the thematic modality. The analyzed collection can be thematized into the following categories: (1) Compromised body image and interactions, (2) Spirituality, (3) Loss of control over life, (4) Going on with life, and (5) Association with ethnic-racial issues. Despite advances in biomedicine, we observed that representations of breast cancer still have metaphors associated with cancer in the last century. We conclude that, among other aspects, care for women with breast cancer cannot be guided only by biomedical and epidemiological approaches since this disease is traversed by knowledge that competes with these approaches.

Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study

In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values. This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. National Health and Medical Research Council, Australian Research Council.

A Comprehensive Review of the Global Epidemiology, Clinical Management, Socio-Economic Impacts, and National Responses to Long COVID with Future Research Directions.

Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID's epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management; Conclusions: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Addressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.

Rheumatoid arthritis increases the risk of heart failure: results from the cross-sectional study in the US population and mendelian randomization analysis in the European population.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Among its various complications, heart failure (HF) has been recognized as the second leading cause of cardiovascular death in RA patients. The objective of this study was to investigate the relationship between RA and HF using epidemiological and genetic approaches. The study included 37,736 participants from the 1999-2020 National Health and Nutrition Examination Survey. Associations between RA and HF in the US population were assessed with weighted multivariate logistic regression analysis. A two-sample Mendelian randomization (MR) analysis was employed to establish the causal relationship between the two variables. The primary analysis method utilized was inverse variance weighting (IVW). Additionally, horizontal pleiotropy and heterogeneity were assessed to account for potential confounding factors. In cases where multiple independent datasets were accessible during MR analysis, we combined the findings through a meta-analytical approach. In observational studies, the prevalence of HF in combination with RA reached 7.11% (95%CI 5.83 to 8.39). RA was positively associated with an increased prevalence of HF in the US population [odds ratio (OR):1.93, 95% confidence interval (CI):1.47-2.54, P < 0.0001]. In a MR analysis utilizing a meta-analytical approach to amalgamate the results of the IVW method, we identified a significant causal link between genetically predicted RA and a heightened risk of HF (OR = 1.083, 95% CI: 1.028-1.141; P = 0.003). However, this association was not deemed significant for seronegative RA (SRA) (OR = 1.028, 95% CI: 0.992-1.065; P = 0.126). These findings were consistent across sensitivity analyses and did not indicate any horizontal pleiotropy. RA correlates with an elevated prevalence of HF within the US population. Furthermore, genetic evidence derived from European populations underscores a causal link between RA and the risk of HF. However this association was not significant in SRA.

Urgent appeal for expanded initiatives in gastric motility disorders across low and middle-income countries: illustrating the example of gastroparesis.

This paper provides a comprehensive exploration of the current state of gastroparesis management in low and middle-income countries (LMICs), emphasising recent innovations, persistent challenges, and future prospects. Gastroparesis, a condition characterised by delayed stomach emptying, presents debilitating symptoms and is notably linked to neuropathic disorders, including diabetes mellitus. Despite an apparent higher prevalence in LMICs compared to the global average, epidemiological data remains scarce. The paper highlights pioneering research in Pakistan, Brazil, and China, showcasing a transformative shift toward comprehensive studies that delve into nuanced aspects of gastroparesis epidemiology, gender-specific patterns, and innovative therapeutic approaches such as acupuncture. However, challenges impeding clinical management and research in LMICs are identified, encompassing the absence of extensive epidemiological studies, lack of treatment guidelines, and the scarcity of specialised training programs for healthcare professionals. These challenges are intertwined with broader issues such as limited healthcare infrastructure, resource disparities, and healthcare workforce shortages. The paper proposes a multifaceted approach for addressing these challenges, involving international collaboration, capacity building, and the integration of gastroparesis management into primary healthcare services. Strategies to combat brain drain, such as collaborative agreements akin to the UK-South Africa Memorandum of Understanding, are advocated.

Understanding the psychodynamics of the pathway to suicide

This paper describes the current understanding of the psychodynamics of the pathway to suicide and argues that the limitations of current epidemiological and observational approaches often overlook crucial psychodynamic factors. It describes how an underlying vulnerability in the capacity to process emotions can lead to unbearable pain, where death is perceived as the only escape. The intense emotional states following life’s losses can then precipitate a profound division within the self. This internal split is characterised by a detached, destructive ‘perpetrator’ aspect and a vulnerable ‘victim’ aspect, with the former often overpowering the latter in the lead-up to suicide through suicidal fantasies of life after death. Drawing on data from various sources, including case studies, mental health audits, and coroner’s reports, the paper assesses the practical efficacy of understanding suicide through a psychodynamic lens. This approach aims to provide more effective intervention strategies, not just by preventing suicide but also by addressing the needs of those left bereaved, who often suffer from complex grief and an elevated risk of suicide themselves. By shifting focus from solely preventive measures to a deeper understanding of the underlying psychological mechanisms, this research advocates for a more holistic approach to suicide prevention. It calls for a shared philosophical inquiry into the nature of human existence and the existential conflict between the will to live and the impulse to die, suggesting that a more nuanced comprehension of these dynamics could lead to better support systems both for those at risk and those bereaved.

Phylogenetic inference of inter-population transmission rates for infectious diseases.

Estimating transmission rates is a challenging yet essential aspect of comprehending and controlling the spread of infectious diseases. Various methods exist for estimating transmission rates, each with distinct assumptions, data needs, and constraints. This study introduces a novel phylogenetic approach called transRate, which integrates genetic information with traditional epidemiological approaches to estimate inter-population transmission rates. The phylogenetic method is statistically consistent as the sample size (i.e. the number of pathogen genomes) approaches infinity under the multi-population susceptible-infected-recovered model. Simulation analyses indicate that transRate can accurately estimate the transmission rate with a sample size of 200 ~ 400 pathogen genomes. Using transRate, we analyzed 40,028 high-quality sequences of SARS-CoV-2 in human hosts during the early pandemic. Our analysis uncovered significant transmission between populations even before widespread travel restrictions were implemented. The development of transRate provides valuable insights for scientists and public health officials to enhance their understanding of the pandemic's progression and aiding in preparedness for future viral outbreaks. As public databases for genomic sequences continue to expand, transRate is increasingly vital for tracking and mitigating the spread of infectious diseases.

Epidemiological Characteristics of Chronic Renal Failure Patients of Hodeidah, Yemen in 2023

Chronic renal failure (CRF) is an emergent worldwide public health problem. The increasing incidence of CRF warrants a need for an epidemiological approach to better understand the disease and its prevention. Therefore, the study aims to describe the epidemiological characteristics of chronic renal failure patients in Hodeidah, Yemen. The study included 560 patients with CRF in retrospective study (a case series based on medical files) in Center of Dialysis and Renal Diseases of Hodeidah, Yemen from 1st January 2023 to 31st December 2023. The patients were diagnosed based on evidence – based clinical practice guideline of all stages of CRF that was extracted from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKFKDOQI). Epidemiological data were reported with ethical approval consideration, data obtained were analyzed. 560 cases were diagnosed with renal failure, 555 patients (99.107 %) of them were diagnosed with CRF and 5 patients (0.89 %) were diagnosed with acute renal failure (ARF). CRF patients was founded 61.81 % in the males while 38.11 % in the females. However, this difference was statistically significant (X2= 30.921; p &lt; 0.00001). The age range of patients was from 5 to 95 years, where 54.64% of cases occurred more than 50 years then 39.28 % between 18 to 49 years and the lower frequency was in children less than 18 years (5.22%) with different significant ( X2= 226.314 ; p &lt; 0.00001). In addition, 81.98 % of patients in rural and 18.02 % in urban. The maximum cases were reported in summer session namely 13.21 % in July and 11.25 % in August. On the other hand , the major causes were chronic diseases 406 case (73.14 %) that diagnosed and recorded , 161 case (29 %) of hypertension ,132 case (23.78 %) of diabetes , 113 (20.36 %) of inflammation nephrolithiasis obstructive uropathy , 8 cases (1.44 %) of genetic polycystic renal disease , and 4 cases ( 0.72 % ) of sedative narcotic addiction and 137 case (24.68%) of unknown causes with different significant ( X2= 119.00 ; p &lt; 0.00001). The chronic diseases namely diabetes and hypertension were the major causes reported to develop the CRF, therefore, to prevent the development of CRF based on center for control diseases and control (CDC), managing risk factors.

Serological and Molecular Survey of Babesia ovis in Healthy Sheep in Türkiye

Babesiosis, caused by Babesia ovis, is a major seasonal issue in sheep, particularly in countries like Türkiye with high Rhipicephalus bursa tick populations. Previous studies employing various methods such as microscopy, serology, or molecular techniques have reported different epidemiological data concerning ovine babesiosis. Addressing this knowledge gap, our study employed a combined nested PCR (nPCR)/indirect ELISA (iELISA) approach, analyzing blood samples collected from 414 sheep between April and July 2023 using both techniques. nPCR amplified the 18S ribosomal RNA gene of B. ovis and determined a molecular prevalence of 1.9%. Conversely, serological testing using iELISA targeted the BoSA1 antigen and revealed a significantly higher positivity rate of 59.9% for anti-B. ovis antibodies. The temporary presence of Babesia after recovery reduces nPCR sensitivity, resulting in lower molecular prevalence. However, even if Babesia is not present in the host, anti-B. ovis antibodies remain in the serum for a long time and can be detected serologically. Our study underscores the necessity of concurrently employing molecular and serological methods for an accurate assessment of B. ovis prevalence. It highlights the importance of comprehensive epidemiological approaches for effective disease management in sheep populations.

Anencephaly in Slovakia and Czech Republic: embryogenesis, risk factors, epidemiology and preventative approaches

Anencephaly in Slovakia and Czech Republic: embryogenesis, risk factors, epidemiology and preventative approaches

Unraveling the link between heavy metals, perfluoroalkyl substances and depression: Insights from epidemiological and bioinformatics strategies

Heavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be −1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects.

Quantitative analysis of social influence and digital piracy contagion with differential equations on networks

Illegal file sharing of copyrighted contents through popular file sharing networks poses an enormous threat to providers of digital contents, such as, games, softwares, music and movies. Though empirical studies of network effects on piracy is a well-studied domain, the dynamics of peer effect in the context of evolving social contagion has not been enough explored using dynamical models. In this research, we methodically study the trends of online piracy with a continuous ODE approach and differential equations on graphs to have a clear comparative view. We first formulate a compartmental model to study bifurcations and thresholds mathematically. We later move on with a network-based analysis to illustrate the proliferation of online piracy dynamics with an epidemiological approach over a social network. We figure out a solution for this online piracy problem by developing awareness among individuals and introducing media campaigns, which could be a valuable factor in eradicating and controlling online piracy. Next, using degree-block approximation, network analysis has been performed to investigate the phenomena from a heterogeneous approach and to derive the threshold condition for the persistence of piracy in the population in a steady state. Considering the dual control of positive peer influence and media-driven awareness, we examine the system through realistic parameter selection to better understand the complexity of the dynamics and suggest policy implications.

Learning Lessons from the COVID-19 Pandemic-A Qualitative Assessment of the Experiences of Pregnant Latinas Infected with COVID-19 and Their Perspectives on Vaccination.

To examine the experiences of pregnant Hispanic/Latine people with COVID-19, as well as their perspectives on COVID-19 vaccination in pregnancy. We interviewed birthing parents who received care from a teaching hospital in California and tested positive for COVID-19 during pregnancy or delivery. We analyzed transcripts using the constant comparative method for analyzing data to using a phenomological epidemiological approach. We used root cause analysis to identify consistent themes across interviews and assess relationships between social determinants of health and COVID-19 infectivity. We interviewed 14 women from November 2021 to June 2022. Participants reported COVID-19 adversely impacted their clinical care and well-being during pregnancy or postpartum. Impacts among Spanish-speaking participants included unexpected financial hardships, challenges navigating in-patient experiences, and difficulty securing reliable childcare. While most participants were at least partially vaccinated, participants also described doubts and concerns about the vaccine. Our findings suggest that Spanish-speaking Hispanic/Latine patients could benefit from receiving more information about COVID-19 in pregnancy from their healthcare providers. Leveraging familial and social networks, providing reliable information in people's preferred language, and increasing communication through trusted partners may also help combat vaccine hesitancy.

Missouri’s Overdose Field Report: descriptive analysis, survival trends, and naloxone dosing patterns from a community-based survey tool, 2018–2022

ABSTRACT Background: Missouri’s Overdose Field Report (ODFR) is a community-based reporting system which intends to capture overdoses which may not be otherwise recorded. Objectives: Describe the factors related to non-fatal overdoses reported to Missouri’s ODFR. Methods: This study used a descriptive epidemiological approach to examine the demographics and circumstances of overdoses reported to the ODFR. We used binary logistic regression to evaluate factors associated with survival and ordinal logistic regression to evaluate factors associated with number of doses used. Factors were chosen based on their relevance to overdose education and survival, and naloxone distribution. Results: Between 2018 and 2022, 12,225 overdoses (67% male; 78% White) were reported through the ODFR, with a 96% (n = 11,225) survival rate. Overdose survival (ps < .02) was associated with younger age (OR = .58), no opioid and stimulant co-involvement (OR = .61), and private location (OR = .48). Intramuscular naloxone in particular was associated with a significantly higher odds of survival compared to nasal naloxone (OR = 2.11). An average of 1.6 doses of naloxone per incident were administered. Additional doses were associated (ps < .02) with being older (OR = .45), female (OR = .90), nasal naloxone (versus intravenous) (OR = .65), and the belief fentanyl was present (OR = 1.49). Conclusion: Our reporting form provides a comprehensive picture of the events surrounding reported overdoses, including factors associated with survival, how much naloxone was used, and the effects of respondents believing fentanyl was involved. Missouri’s report can provide support for current naloxone dosing, contextualize refusing post-overdose transport, and can be used to improve overdose response by community and first responders.

Abstract PO5-10-03: A Translational Epidemiologic Approach to Understand Disparities in Triple Negative Breast Cancer: Integrating Germline Genomics, Genetic Ancestry, and Neighborhood Disadvantage

Abstract Background: Triple-negative breast cancer (TNBC) disproportionately affects women of West African ancestry and those living in neighborhood disadvantage (ND). However, these studies were limited in their ability to control for both ancestry and socioeconomic data. To overcome this limitation, we utilized the epidemiologic-genomic infrastructure of the Miami Breast Cancer Disparities (MBCD) study to evaluate the impact of ND on relative risk (RR) of TNBC, independent of West African ancestry. Methods: A prospective cohort of 502 women with breast cancer enrolled in the MBCD study from 2020-2022. Genetic ancestry, median neighborhood-level income quartiles (ND), germline genetic mutations, and tumor characteristics were assessed. Multinomial logistic regression was used to determine the RR between West African ancestry and TNBC (compared to ER+/HER2- and HER2+ disease) after controlling for access to care measures which might impact TNBC distributions and known TNBC risk factors (e.g., age, ND, BRCA 1 mutation, obesity, screening mammography). Results: Of the 502 women, 333 (66.33%) had ER+/HER2- disease, 67 (13.35%) had ER+/HER2+ disease, 22 (4.38%) had ER-/HER2+ disease, and 80 (15.94%) had TNBC. On univariable analysis, the highest West African quartile (RR 3.58 95%CI 1.72-7.42, p&amp;lt; 0.001), a BRCA 1 mutation (RR 7.89 95%CI 2.25-27.64, p=0.001) were associated with a higher RR of TNBC. Conversely, decreasing ND was associated with a lower RR of TNBC (RR 0.42 95%CI 0.21-0.83, p=0.013). On covariate adjusted multivariable analysis, decreasing ND (RR 0.45 95%CI 0.22-0.99, p=0.047) and a BRCA 1 mutation (RR 12.68 95%CI 3.19-50.35, p&amp;lt; 0.0001) were both significantly associated with TNBC compared to ER+/HER2- and HER2+ disease. Conclusions: To our knowledge, this prospective study is the first to evaluate the combined impact of genetic ancestry, germline genomics, and social factors on RR of TNBC. We discovered that ND and BRCA 1 mutations are independent predictors of TNBC, even after accounting for known TNBC risk factors (e.g., West African ancestry). These findings suggest a potential association between ND and TNBC, thus emphasizing the importance of a translational epidemiologic approach to understand TNBC disparities that considers both genomic and non-genomic factors. Table. Adjusted Multinomial Logistic Regression of Patient Genetic Ancestry, Sociodemographic and Tumor Characteristics Predictors of Breast Cancer Subtype Citation Format: Neha Goel, Alexandra Hernandez, Susan Kesmodel, Erin Kobetz, Nipun Merchant, Timothy Rebbeck. A Translational Epidemiologic Approach to Understand Disparities in Triple Negative Breast Cancer: Integrating Germline Genomics, Genetic Ancestry, and Neighborhood Disadvantage [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-03.

Protocol for CARES–HAPIN: an ambidirectional cohort study on exposure to environmental tobacco smoke and risk of early childhood caries

IntroductionPrenatal and postnatal exposure to environmental tobacco smoke (ETS) has been linked with early childhood caries (ECC), but the specific molecular mechanisms and pathways remain largely unknown. The Caries Risk...

Pulmonary Hypertension Associated with Chronic Lung Disease

Abstract: Patients with Chronic Lung Disease (CLD) are frequently burdened by pulmonary hypertension (PH), which is associated with reduced functional capacity, poor quality of life, increased oxygen requirements, and increased morbidity and mortality. The development of PH associated with chronic lung disease (PH-CLD) is complex and multifactorial and varies between different types of CLD. In this review, we provide an update on PH-CLD, with a particular focus on Interstitial Lung Disease (ILD), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and obesity hypoventilation syndrome (OHS). We discussed epidemiology, histopathology, pathophysiology, diagnostic evaluation, and treatment approaches. There are limited data on the use of pulmonary arterial hypertension-specific treatments in PH-CLD, so it has been proposed to phenotype patients based on their degree of pulmonary vascular disease to guide individualized care. The heterogeneity within PH-CLD highlights the importance of identifying novel molecular pathways unique to each subgroup to ultimately achieve precision medicine.

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.