High Incidence Research Articles

Abstract A118: Barriers and facilitators to cervical cancer screening among older Hispanic women living in San Antonio, TX

Abstract Background: Disparities among Hispanic women getting screened for cervical cancer compared to non-Hispanic White women continue to exist, despite Hispanic women having higher incidence and mortality rates of cervical cancer. Previous work has shown limited knowledge and awareness about cervical cancer and screening, low health literacy, and cultural aspects such as fatalism as barriers to screening. On the other hand, having health insurance, a family history of cervical cancer and religiosity have been found to facilitate cervical cancer screening among Hispanic women. Moreover, in Texas, research has shown that women older than 50 and Hispanic women have lower rates of screening. Methods: Informed by the social determinants of health framework, we are interviewing Hispanic women living in San Antonio, TX about their experiences regarding cervical cancer screening. Questions cover the areas of knowledge about cervical cancer and cervical cancer screening, and barriers and facilitators to cervical cancer screening. We have completed 11 out of 36 planned interviews. Data analysis is guided by applied thematic analysis techniques. Preliminary Results: Currently, ages range from 50 to 64 years old. Most women are married and half are retired. Preliminary analysis shows continued low levels of knowledge about cervical cancer and screening. Barriers include feelings of fear and embarrassment about the test, physician’s gender, and access to healthcare, such as issues with transportation. Facilitators include physician’s attitude, clinic reminders, and having health insurance. Conclusion: More research is needed to understand and address barriers and facilitators to cervical cancer screening in this age group. Targeted public health efforts, including educational and multilevel interventions, should continue to increase knowledge about cervical cancer, and acceptability and access to cervical cancer screening among older Hispanic women living in San Antonio, TX. Citation Format: Coralia Vázquez-Otero, Audrey Cordova, Rita Pedraza, Selena Baglini, Amelie G. Ramírez. Barriers and facilitators to cervical cancer screening among older Hispanic women living in San Antonio, TX [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A118.

Abstract A031: Methylomic Biomarkers Associated with Prostate Cancer in Black Men

Abstract Introduction: The prostate cancer (PCa) disparity remains the highest cancer disparity in the US, with Black men facing an estimated 78% higher incidence and 230% higher mortality than White men. However, current understanding of risk factors for PCa such as socioeconomic status (SES), diet, and genetics cannot fully explain these disparities. Our objective is to examine DNA methylation (DNAm) markers in a cohort of Black men and assess their associations with PCa status. Methods: We randomly selected 100 Black men for DNAm profiling (50 cases diagnosed with clinically significant (Gleason Grade 3+) prostate cancer and 50 age-matched controls) from two larger cohorts. The cohorts recruited 400 Black men who were newly diagnosed with sporadic PCa as well as 400 controls matched on age and race. All men were 40-79 at recruitment and were enrolled from urology clinics at five Chicago-area medical institutions. All PCa cases underwent a transrectal prostate biopsy for abnormal prostate-specific antigen (PSA) or digital rectal exam and had a histologically confirmed prostate cancer and were not previously diagnosed with PCa. All men in the control group had been recruited from community prostate cancer screening events or were referred to participating urology clinics and had a negative prostate biopsy for a PSA <10ng/ml and were not diagnosed with PCa for 2 years of follow-up. Men with prior PCa diagnosis or conditions known to affect PSA levels were excluded. After enrollment and informed consent, all men provided demographic and lifestyle data via three questionnaires, followed by venipuncture for DNA collection. These specimens were obtained using buffy coat extraction after red blood cell lysis, centrifugation, and pipetting off the overlying plasma and buffy coat for freezing followed by Illumina EPIC arrays for DNAm assays. We examined DNAm markers in gene promoter regions associated with PCa using logistic regression and adjusted for multiple testing using Bonferroni correction. All models controlled for age, BMI, smoking status, first degree family history of PCa, blood cell types, and technical control variables. Results: We found 2,180 CpG sites in gene promoter regions associated with any PCa in this population. The top ten strongest associations identified in our models include loci on genes that have already been associated with prostate cancer progression (MAFG, FAM65B, OSM, PRKAG2), risk (SLC11A1, LAT), and metastasis (S1PR4) as well as immune system functioning (RAP1GAP2). Conclusions: Our initial findings suggest that DNAm markers may be useful predictors of clinically significant PCa status among Black men. Additional research is currently ongoing to expand the sample size of the DNAm profiling and to explore links between these loci and social determinants of health, as well as associations with more advanced (i.e., higher Gleason Grade) PCa. Citation Format: Brian T. Joyce, Yishu Qu, Jun Wang, Kai Zhang, Zequn Sun, Lifang Hou, Adam B. Murphy. Methylomic Biomarkers Associated with Prostate Cancer in Black Men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A031.

Abstract B083: Community-based knowledge-to-action translation to improve early detection of prostate cancer among Black individuals

Abstract Introduction: Black individuals have 70-80% higher incidence and 120% higher mortality from prostate cancer when compared to all other groups in the US. This is the largest racial disparity in cancer-related mortality in the US and has persisted over the last five decades despite improvements in the diagnosis and treatment of prostate cancer. Our previous work demonstrated that intensified screening practices could reduce prostate cancer mortality among Black individuals. Challenges impede the translation of these findings into real-world interventions and practices. The objective of this study was to design a patient-centered and culturally tailored knowledge toolkit to improve the knowledge and awareness of prostate-specific antigen (PSA) testing in Black individuals to facilitate informed shared-decision making between Black patients and primary care providers. Methods: Using a community-partnered participatory research approach, we convened a working group of Black prostate cancer survivors and community advocates, and clinicians, researchers, and health communications specialists. During monthly meetings, the working group followed Graham’s Knowledge-to-Action framework to synthesize information from: 1) peer-reviewed literature on the use of shared decision-making aids; 2) interviews conducted by our research team with Black individuals regarding barriers and facilitators to access PSA testing; and 3) community input on PSA testing and prostate cancer early detection. We then facilitated four iterative design sessions with the working group to develop recommendations for toolkit content, framing, and format. Results: With the working group, we designed a comprehensive set of resources to increase knowledge and awareness of PSA testing for early detection of prostate cancer among Black individuals. The design framework includes detailed recommendations on the content, framing, and format for resources contained in the toolkit. Recommendations encompass: 1) interactive web-based documents that cover comprehensive information about prostate cancer risk and screening; 2) printable shared decision-making documents that present evidence-based information about the use of PSA testing to guide conversations between Black individuals and their primary care providers; and 3) educational videos focused on prostate cancer fundamentals and dispelling common misconceptions about prostate cancer risk and screening, with content delivered by Black prostate cancer survivors and interviews with Black providers and prostate cancer researchers. Conclusion: This study addressed the need for a community-developed approach to increasing knowledge and awareness about prostate cancer screening and early detection in an accessible, culturally tailored, and accurate manner. We used a collaborative process that centered the experiences of Black prostate cancer survivors and advocates in the design of a toolkit that can facilitate decision-making discussions between Black individuals and their care providers for use of PSA testing for prostate cancer screening. Citation Format: Jenney R. Lee, Sung Min Kim, Yohali Burrola- Mendez, Dante' Morehead, Marty Chakoian, Michael Ware, Kojo Ward, Floyd Gossett, Vida Henderson, Patricia Egwuatu, Burcu Darst, John Masembe, Erika M. Wolff, Yaw A Nyame. Community-based knowledge-to-action translation to improve early detection of prostate cancer among Black individuals [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B083.

Abstract C162: Prespecified interim analysis of the DARolutamide ObservationaL (DAROL) study in Black/African American patients with nonmetastatic castration-resistant prostate cancer (nmCRPC)

Abstract Introduction: Black/African American (B/AA) men are disproportionately affected by prostate cancer, having higher incidence and mortality rates compared with other ethnic/racial populations. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration and limited potential for drug–drug interactions. In ARAMIS (NCT02200614; phase 3), DARO significantly improved metastasis- free survival (MFS) by ∼2 years and reduced the risk of death by 31% vs placebo in patients with nmCRPC, with favorable tolerability. The DAROL study (NCT04122976) is assessing the real- world safety and effectiveness of DARO in patients with nmCRPC. Here we report a subgroup analysis of B/AA patients from the prespecified third interim analysis (IA3). Methods: DAROL is an ongoing, global, open-label, single-arm, non-interventional study in patients aged ≥18 years with nmCRPC for whom the decision to be treated with DARO was decided pre-enrollment. The primary endpoint is safety, including incidence and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints include MFS, overall survival (OS), prostate-specific antigen (PSA) progression, and PSA response. IA3 was conducted when 550 patients completed ≥6 months of treatment (data cut-off July 17, 2023). Results: Of 550 patients, 199 (36%)/191 (35%)/152 (28%)/8 (2%) were from Europe/North America/Asia Pacific/Latin America, respectively. All 23 B/AA patients were from North America and represented 12% of this cohort. At baseline, PSA levels (median 4.2 ng/mL vs 4.0 ng/mL) and PSA doubling time (median 5.9 months vs 5.3 months) were similar in the B/AA and overall DAROL population, whereas B/AA patients were generally younger than the overall population (median 74 [range 49–94] vs 79 [range 29–98] years, respectively) with proportionately fewer patients aged ≥75 yrs (12 [52%] vs 387 [70%]), fewer B/AA patients (33%) had a Gleason score ≥8 vs the overall population (53%), and proportionally more B/AA patients (94%) had ECOG PS 0 vs the overall population (64%). Consistent with the DAROL IA3 overall population, DARO showed a favorable safety profile in the B/AA subgroup, and TEAEs were mostly grade 1/2. In the DAROL IA3 overall population, the proportion of patients who achieved a 90% reduction in PSA from baseline was 54%, while MFS and OS rates at 2 years were 78% and 88%, respectively. Effectiveness and safety outcomes for the B/AA subgroup will be presented. Conclusion: Findings from the DAROL IA3 B/AA subgroup were similar to the overall population and consistent with the favorable efficacy and safety profile of DARO observed in the ARAMIS B/AA subgroup and overall population. Citation Format: Evan Y. Yu, Christopher Pieczonka, Hiroyoshi Suzuki, Alberto Briganti, Murilo Luz, Declan Murphy, Patrick Adorjan, Mercedeh Ghadessi, Frank Verholen, Andrew J. Armstrong. Prespecified interim analysis of the DARolutamide ObservationaL (DAROL) study in Black/African American patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C162.

Respiratory pathogen dynamics in community fever cases: Jiangsu Province, China (2023–2024)

BackgroundRespiratory infectious diseases have the highest incidence among infectious diseases worldwide. Currently, global monitoring of respiratory pathogens primarily focuses on influenza and coronaviruses. This study included influenza and other common respiratory pathogens to establish a local respiratory pathogen spectrum. We investigated and analyzed the co-infection patterns of these pathogens and explored the impact of lifting non-pharmaceutical interventions (NPIs) on the transmission of influenza and other respiratory pathogens. Additionally, we used a predictive model for infectious diseases, utilizing the commonly used An autoregressive comprehensive moving average model (ARIMA), which can effectively forecast disease incidence.MethodsFrom June 2023 to February 2024, we collected influenza-like illness (ILI) cases weekly from the community in Xuanwu District, Nanjing, and obtained 2046 samples. We established a spectrum of respiratory pathogens in Nanjing and analysed the age distribution and clinical symptom distribution of various pathogens. We compared age, gender, symptom counts, and viral loads between individuals with co-infections and those with single infections. An autoregressive comprehensive moving average model (ARIMA) was constructed to predict the incidence of respiratory infectious diseases.ResultsAmong 2046 samples, the total detection rate of respiratory pathogen nucleic acids was 53.37% (1092/2046), with influenza A virus 479 cases (23.41%), influenza B virus 224 cases (10.95%), and HCoV 95 cases (4.64%) being predominant. Some pathogens were statistically significant in age and number of symptoms. The positive rate of mixed infections was 6.11% (125/2046). There was no significant difference in age or number of symptoms between co-infection and simple infection. After multiple iterative analyses, an ARIMA model (0,1,4), (0,0,0) was established as the optimal model, with an R2 value of 0.930, indicating good predictive performance.ConclusionsThe spectrum of respiratory pathogens in Nanjing, Jiangsu Province, was complex in the past. The primary age groups of different viruses were different, causing various symptoms, and the co-infection of viruses did not correlate with the age and gender of patients. The ARIMA model estimated future incidence, which plateaued in subsequent months.

HUMAN PAPILLOMAVIRUS, CLINICAL, DERMATOLOGICAL AND GYNECOLOGICAL APPROACH

Introduction: Human papillomavirus (HPV) infection is associated with a wide range of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through multiple benign clinical presentations, including cutaneous and mucosal disease, to malignant and premalignant conditions. Cervical cancer is the fourth cancer with the highest incidence in women in the world, being the second cause of cancer death in women between 15 and 44 years of age, one of the risk factors for this cancer is the human papillomavirus. Objective: to detail the current information related to human papillomavirus, description, etiology, epidemiology, pathophysiology, anamnesis, physical examination, evaluation, treatment, differential diagnosis, prognosis, prevention and complications taking into account a clinical, dermatological and gynecological approach. Methodology: a total of 27 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 18 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: human papillomavirus, HPV, dermatosis, warts, infection, papanicolau, tumor virus infections. Results: HPV has been associated with the development of laryngeal, mouth, lung and anogenital cancers. Subtypes 6 and 11 are low risk and are usually associated with the formation of condylomas and low-grade precancerous lesions. Subtypes 16 and 18 are high-risk and are responsible for high-grade intraepithelial lesions that progress to malignant neoplasia. There are more than 180 HPV subtypes.The prevalence of genital HPV in adults aged 18-59 years is about 45.2% in males and 39.9% in females. The prevalence of high oncogenic risk HPV genotypes is 2.26%; (95%CI: 1.75-2.78), with the most common genotype being 16 (28.89%). Cervical cancer screening with cytology has significantly reduced the incidence and mortality of this type of cancer in developed countries, despite the fact that its sensitivity for detecting CIN2+ is around 66%. Conclusions: it is of remarkable importance to know the human papillomavirus outlook, especially because it is linked to a number of underlying clinical manifestations both benign, premalignant and malignant conditions. The authors recommend prevention, especially suggesting that boys and girls be vaccinated against HPV starting at 11 to 12 years of age, in addition to the other measures outlined in the article. It is important to understand that HPV alone does not cause cancer, but requires triggering factors such as smoking, folate deficiency, exposure to ultraviolet light, immunosuppression and pregnancy. Individuals with cutaneous warts have numerous treatment alternatives available, including surgical removal, cryotherapy, irritant or immunomodulatory drugs, and laser removal. KEY WORDS: HPV, infection, pap smear, warts.

Effectiveness of long-term low-dose aspirin in the prevention of gastric cancer after Helicobacter pylori eradication: study design and rationale of Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT)

BackgroundIn addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication.Methods/designAGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC.DiscussionIn addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study’s results may help policymakers and researchers update the strategies for GC prevention.Trial registrationThis trial with the registry name of “The effect of Low-dose Aspirin in the Prevention of Gastric Cancer” was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.

Impact of Covid-19 pandemic on HIV testing, recent infections and annualized incidence among cisgender men who have sex with men and transgender women in Brazil

Background: The Covid-19 pandemic had great impact on HIV care and prevention worldwide, including in Brazil. We compared HIV testing, recent infection, and annualized incidence according to Covid-19 pandemic period among men who have sex with men (MSM) and transgender women (TGW). Setting: HIV/STI testing, prevention and treatment referral service in Rio de Janeiro, Brazil Methods: We used Maxim HIV-1 Limiting Antigen Avidity EIA as part of recent infection testing algorithm to identify recent HIV infections and estimate annualized HIV incidences in pre- (March/2018-February/2020) and post-Covid-19 pandemic onset period (March/2020-January 2022). Multivariable logistic regression model assessed factors associated with recent HIV infection. Results: Among 4590 MSM and TGW, 593 (12.9%) tested positive for HIV and 119 (2.6%) were identified as having recent infection. Percentage of recent HIV infection did not differ between Covid-19 periods. Overall annualized HIV incidence rates were 6.0% (95%CI:4.2-7.7) and 6.6% (95%CI:4.3-9.0) in pre- and post-Covid-19 periods, respectively. During the post-Covid-19 period, higher incidence rates were observed among TGW (8.4%[95%CI:2.9-13.9]), those aged 18-24 years (7.8%[ 95%CI:4.0-11.7]), Black race (7.9%[95%CI:3.8-12.0]), and with <12 years of schooling (7.8%[95%CI:4.8-10.8]). Incidence rates were significantly higher in the post-Covid-19 period for those aged>30 years and TGW, and lower for those with more years of schooling. Conclusion: HIV incidence estimates remain high among MSM and TGW in Brazil, especially among the most vulnerable. The consequences of the Covid-19 pandemic on the HIV epidemic will likely persist and contribute to worsening HIV outcomes.

Global burden of chronic kidney disease in adolescents and young adults, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

The global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15-39). We aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019. We analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors. From 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI). The age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.

Patterns of incidence and characteristics of youth with new-onset diabetes mellitus during the COVID era

Objectives: The incidence of diabetes mellitus (DM) in children, adolescents, and young adults has been on the rise for many decades. The COVID-19 pandemic has been associated with a dramatic increase in new cases of pediatric DM and a shift in the seasonal pattern of incidence. We aimed to determine the incidence of DM and its subtypes during the COVID-19 pandemic (2020–2022) and pre-pandemic (2017–2019). We sought to assess for a difference in seasonality and temporal pattern of new-onset DM between the two periods and aimed to describe and compare the clinical characteristics of the patients diagnosed during this time. Material and Methods: In this retrospective chart review, data were collected from medical records for all patients aged 1–21 years diagnosed with DM at our center between January 1, 2017 and December 31, 2022. Results: The incidence of DM at our center increased 38% during the pandemic (incidence rate ratio [IRR] 1.38, 95% confidence interval; [CI] 1.20–1.58). The incidence of type 1 diabetes (T1D) increased 11% (IRR 1.11, 95% CI 1.01–1.23) and the median body mass index percentile increased for those diagnosed during the pandemic (P = 0.012). The incidence of type 2 diabetes (T2D) increased 238% (IRR 3.38, 95% CI 2.17–5.28) during the pandemic, with the highest rate of diagnosis in a younger age group (P = 0.015). The pattern of incidence of T1D shifted from lowest in the summer pre-pandemic to highest in the summer during the pandemic (IRR 1.82, 95% CI 1.22–2.72). The overall incidence trend for DM, T1D, and T2D, peaked in spring 2021 and then declined until it stabilized in summer 2022. Conclusion: Our study showed a persistent increase in the incidence of both T1D and T2D in the pediatric population during the pandemic. Those diagnosed with T2D during the pandemic were younger than those diagnosed in the pre-pandemic period. There was a shift in seasonal pattern of T1D incidence during the pandemic with the highest rates of incidence during the summer. Further studies are needed to evaluate the underlying mechanisms of the persistent increase in incidence.

Innate immunity gene Nod2 protects mice from orthotopic breast cancer

BackgroundNod2 is involved in innate immune responses to bacteria, regulation of metabolism, and sensitivity to cancer. A Nod2 polymorphism is associated with breast cancer, but the role of Nod2 in the development and progression of breast cancer is unknown.MethodsHere, we tested the hypothesis that Nod2 protects mice from breast cancer using the 4T1 orthotopic model of mammary tumorigenesis. WT and Nod2−/− mice were injected with 4T1 mammary carcinoma cells and the development of tumors was monitored. A detailed analysis of the tumor transcriptome was performed and genes that were differentially expressed and pathways that were predicted to be altered between WT and Nod2−/− mice were identified. The activation of key signaling molecules involved in metabolism and development of cancer was studied.ResultsOur data demonstrate that Nod2−/− mice had a higher incidence and larger tumors than WT mice. Nod2−/− mice had increased expression of genes that promote DNA replication and cell division, and decreased expression of genes required for lipolysis, lipogenesis, and steroid biosynthesis compared with WT mice. Nod2−/− mice also had lower expression of genes required for adipogenesis and reduced levels of lipids compared with WT mice. The tumors in Nod2−/− mice had decreased expression of genes associated with PPARα/γ signaling, increased activation of STAT3, decreased activation of STAT5, and no change in the activation of ERK compared with WT mice.ConclusionsWe conclude that Nod2 protects mice from the 4T1 orthotopic breast tumor, and that tumors in Nod2−/− mice are predicted to have increased DNA replication and cell proliferation and decreased lipid metabolism compared with WT mice.

First manifestation of cardiovascular disease according to age and sex in a Mediterranean country

BackgroundCardiovascular (CV) diseases are the most common cause of death worldwide. This study aimed to investigate the incidence and type of first CV event in a broad cohort of Spaniards, focusing on age and sex differences.MethodsThis was a retrospective study using the SIDIAP database. Subjects aged 30–89 years in 2010 were included. Individuals with prevalent CV disease or atrial fibrillation were excluded. Subjects were followed until the occurrence of a CV event, death, or the study end (December 2016). CV outcomes (coronary heart disease [CHD], cerebrovascular or peripheral artery disease and heart failure [HF]) during follow-up were analyzed. Clinical, anthropometrical, and laboratory data were retrieved from clinical records.ResultsOverall, 3,769,563 at-risk individuals (51.2 ± 15.2 years) were followed for a median of 7 years. The cumulative incidence of a first CV event was 6.66% (men vs. women, 7.48% vs. 5.90%), with the highest incidence (25.97%) among individuals >75 years. HF (29%) and CHD (28.8%) were the most common first events overall; in men it was CHD (33.6%), while in women it was HF and cerebrovascular disease (37.4% and 27.4%). In younger age groups, CHD was more prevalent, with HF in older age groups. Baseline CV risks factors conferred more risk in younger ages and differed between men and women.ConclusionsThe incidence and type of the first CV event in this Mediterranean region were significantly influenced by age and sex. This information is relevant for tailoring primary prevention strategies including the treatment of risk factors.

Global, regional, and national epidemiology of ischemic stroke from 1990 to 2021.

This study aims to examine the global, regional, and national burden of ischemic stroke from 1990 to 2021. We used data from the Global Burden of Disease (GBD) 2021 database to comprehensively assess ischemic stroke indicators globally, regionally, and in 204 countries, including incidence, deaths, disability-adjusted life years (DALYs), estimated annual percentage change (EAPC), and Joinpoint regression analysis. In 2021, there were a total of 7,804,449 cases of ischemic stroke globally (95% uncertainty interval = 6,719,760-8,943,692), with an age-standardized incidence rate (ASIR) of 92.39. This represents a declining trend compared to 1990, with an EAPC of -0.67 (95% confidence interval [CI] = -0.76 to -0.58). Mortality and DALY rates also showed a downward trend (EAPC in age-standardized mortality rate: -1.83, 95% CI = -1.92 to -1.74; EAPC in age-standardized DALY rate = -1.59, 95% CI = -1.68 to -1.50). The burden of ischemic stroke was inversely correlated with gross domestic product. Regionally, from 2014 to 2021, the Caribbean experienced the fastest increase in ASIR (annual percent change = 0.15, 95% CI = 0.13 to 0.18). Among 204 countries, North Macedonia had the highest incidence, mortality, and DALY rates. In addition to metabolic risks, particulate matter pollution and low temperatures were significant environmental and occupational risk factors for ischemic stroke. Smoking and a diet high in sodium were identified as key behavioral risk factors. Ischemic stroke remains a serious global health challenge, and our results from this cross-sectional study suggest that the burden of disease remains high in Eastern Europe, East Asia, Central Asia, and Sub-Saharan Africa.

HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Abstract B090: Evaluating the molecular determinants of PDAC racial health disparities

Abstract Pancreatic cancer is the 3rd leading cause of cancer-related deaths, with a 5-year survival rate of just 13%. Pancreatic ductal adenocarcinoma (PDAC), accounting for over 90% of pancreatic malignancies, has the highest incidence rate, mortality rate, and shortest survival times in non- Hispanic Black (defined here as African and/or African American ancestry) patients compared to other races. To identify molecular features that may contribute to racial health disparities in PDAC, we used quantitative mass spectrometry to determine the proteomic signatures unique to tumor racial origin in a cohort of 30 Caucasian and 12 African American patients. This analysis of the bulk tumor proteome revealed 183 proteins were differentially expressed between these groups. The protein with the highest expression in tumors from Black patients relative to Whites was Ring Finger Protein 2 (RNF2) that acts as an epigenetic transcriptional repressor in developmental processes pertaining to cellular differentiation. To determine the molecular pathways in PDAC regulated by RNF2, chromatin immunoprecipitation and sequencing (ChIP-seq) was performed on MIA-PaCa2 and a primary PDAC cell line derived from a Black patient to identify binding sites for RNF2 in PDAC cells. From the 1,142 replicated peaks identified, RNF2 peaks were localized over the transcription start site of 644 unique transcripts, including GATA6, which is an important determinant in PDAC subtype delineation with higher GATA6 expression associated with the less aggressive and more chemosensitive Classical subtype. Modulating RNF2 levels/activity by exogenous expression, short hairpin RNA (shRNA) knockdown, and small molecule inhibition confirms that GATA6 is a target of RNF2 repression in PDAC. Multi-omic (transcriptomic, proteomic, and phosphoproteomic) characterization was performed on MIA-PaCa2 cells with CRISPR-Cas9 knockout (KO) of RNF2. Differential gene expression (DE) analysis revealed changes in platinum drug resistance, EMT, and innate immune response, which are characteristic of the aggressive Inflammatory PDAC subtype we previously reported using proteomics. Total and phospho-proteomics corroborated these results identifying changes in DNA repair, inflammation response, TNFα mediated signaling, and apoptotic signaling. These results reflect the enrichment of Inflammatory subtype markers in tumors originating in Black patients. In agreement with these results, RNF2 KO shows a significant reduction in migration, as well as an increase in sensitivity to oxaliplatin. Our work identifies differences in the underlying proteome of PDAC tumors associated with tumor racial origin and describes how elevated expression of RNF2 in PDACs from Black patients contribute to inflammation and subtype delineation. This study delineates the associations between tumor racial origin, subtype specification, and response to therapy that could mitigate PDAC health disparities and be broadly applied across all PDAC patients. Citation Format: Anthony E Johansen-Sallee, Alexa M Barber, Henry C.-H. Law, Vignesh Vudatha, Jose Trevino, Nicholas T Woods. Evaluating the molecular determinants of PDAC racial health disparities [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B090.

Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma.

The incidence of primary liver cancer is increasing year by year. In 2022 alone, more than 900000 people were diagnosed with liver cancer worldwide, with hepatocellular carcinoma (HCC) accounting for 75%-85% of cases. HCC is the most common primary liver cancer. China has the highest incidence and mortality rate of HCC in the world, and it is one of the malignant tumors that seriously threaten the health of Chinese people. The onset of liver cancer is occult, the early cases lack typical clinical symptoms, and most of the patients are already in the middle and late stage when diagnosed. Therefore, it is very important to find new markers for the early detection and diagnosis of liver cancer, improve the therapeutic effect, and improve the prognosis of patients. Protein tyrosine phosphatase non-receptor 2 (PTPN2) has been shown to be associated with colorectal cancer, triple-negative breast cancer, non-small cell lung cancer, and prostate cancer, but its biological role and function in tumors remain to be further studied. To combine the results of relevant data obtained from The Cancer Genome Atlas (TCGA) to provide the first in-depth analysis of the biological role of PTPN2 in HCC. The expression of PTPN2 in HCC was first analyzed based on the TCGA database, and the findings were then verified by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting. The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features. Finally, the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining. The results of immunohistochemical staining, qRT-PCR, and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways, including cancer-related pathways, the Notch signaling pathway, and the MAPK signaling pathway. Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways, such as the epithelial mesenchymal transition process. A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group. This study investigated PTPN2 from multiple biological perspectives, revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Risk of anxiety-related sleep disorder in nursing students

Introduction: Anxiety affects 29% of the world's population, with higher incidence in females (77%) and this begins before the age of 18 years. Academic pressure aggravates anxiety and can lead to severe or serious mental health problems. Objective: To correlate anxiety and sleep disorders in university students. Methods: This quantitative, descriptive, cross-sectional study seeks to test hypotheses about anxiety and sleep disorders in 100 nursing students of the Technical University of Ambato through surveys, analyzing data in SPSS and Excel. Results: 85% of the students experience severe levels of anxiety, which can negatively affect their sleep quality and general well-being. Conclusion: Anxiety in university students, especially in health areas, can lead to more serious mental health problems and affect their academic performance and clinical skills. Implementing psychological support and stress management programs is essential to improve their well-being and academic performance.

Post-Traumatic Trigeminal Neuropathic Pain: A Narrative Review of Understanding, Management, and Prognosis.

This study provides an updated overview of the clinical characteristics of post-traumatic trigeminal neuropathic pain (PTNP) resulting from dental procedures or facial trauma, addressing its etiology, prevalence, evaluation, management, and prognosis. PTNP arises from injury to the trigeminal nerve, which governs sensory and motor functions in the maxillofacial region. The prevalence and characteristics of PTNP vary considerably across studies, with a reported prevalence ranging from 1.55% to 13%. The predominant causative factors are dental procedures, particularly third molar removal and implant placement. While gender distribution varies, a trend towards higher incidence in females is observed, particularly within the 40-60-year age group. Anatomically, the mandibular nerve is frequently involved. PTNP presents with a spectrum of symptoms ranging from tingling sensations to severe pain. Diagnostic challenges arise due to the lack of standardized criteria and potential overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can lead to prolonged patient suffering and unnecessary interventions. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating progression to chronic pain. Although nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount. Management strategies for PTNP include non-invasive and surgical interventions, with non-invasive approaches encompassing systemic and local pharmacological management. This narrative review aims to enhance uniformity in PTNP evaluation and treatment approaches, ultimately improving patient care and outcomes.

Short Communication: Novel Di- and Triselenoesters as Effective Therapeutic Agents Inhibiting Multidrug Resistance Proteins in Breast Cancer Cells.

Breast cancer has the highest incidence rate among all malignancies worldwide. Its high mortality is mainly related to the occurrence of multidrug resistance, which significantly limits therapeutic options. In this regard, there is an urgent need to develop compounds that would overcome this phenomenon. There are few reports in the literature that selenium compounds can modulate the activity of P-glycoprotein (MDR1). Therefore, we performed in silico studies and evaluated the effects of the novel selenoesters EDAG-1 and EDAG-8 on BCRP, MDR1, and MRP1 resistance proteins in MCF-7 and MDA-MB-231 breast cancer cells. The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds-novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy.

Estimation of State and district-specific disability adjusted life years (DALYs) due to tuberculosis for Kerala, India, 2017-2020.

Background & objectives Tuberculosis (TB) control programmes routinely use indicators like incidence and mortality. A single indicator, like disability-adjusted life years (DALYs) may yield a more comprehensive burden estimate. This study attempted to estimate the state and district-specific TB burden in Kerala. Methods The sole data source for these computations was the Ni-kshay, notification register for 2017 to 2020, Kerala. Age of the patient and outcome are available in the register. Notified incident TB/1000, the median age of onset of TB, case fatality due to TB, and the median age of mortality were computed using SPSS software. DALYs was calculated using the DALYs package of the R program, using these input parameters. Disability weight was taken as 0.333. The absolute and relative DALY/100,000 population was estimated along with the 95% confidence interval (CI). Results Relative DALYs was highest in 2019 at 1482/100,000 and lowest at 1124/100,000 in the year 2020 during the period 2017 to 2020. The districts, which had the highest incidence were not the same as those with the highest DALYs. Ernakulam and Thrissur districts had the highest burden and Idukki had the least burden. Interpretation & conclusions DALYs estimates for Kerala showed an increasing trend before 2020, which could be due to the increased efforts to detect TB as part of the elimination drive. The study points towards the need for using DALYs as a measure for prioritizing districts for resource allocation.