bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C080: Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth
Authors: Bukenya George , Sloan Anthony , Horbinski Craig , Gupta Anirban Sen , Cameron Scott , Lathia Justin
Published: September 2024

Cancer-related thrombosis is the second leading cause of death for cancer patients, including those with glioblastoma (GBM), the most common primary malignant brain tumor. Patients with GBM have a 30% risk of venous thromboembolism (VTE). High platelet counts, and increased platelet reactivity are associated with poor clinical outcomes in many cancers. While platelets are known to promote progression of tumors, the mechanisms by which these changes in platelet reactivity act as a driver for GBM progression is unknown. Our previous work demonstrated that a subpopulation of glioma cells activates platelets to promote GBM cell growth by intrinsically producing thrombin via a cell intrinsic functional coagulation cascade. These findings provided evidence that glioma cells can readily execute a highly liver-specific gene expression program that contributes to a hyper-thrombotic state in the GBM tumor microenvironment (TME). We now demonstrate thrombin and platelet expression in GBM patient specimen creates a hyper-thrombotic GBM tumor-microenvironment and that GBM patient platelets have increased reactivity compared to healthy patients. Further, genetic targeting of the intrinsic coagulation cascade, via knockdown of coagulation factor 11 (F11) and coagulation factor 12 (F12), reduces glioma cell growth and tumor formation while also decreasing the ability for glioma cells to activate platelets, subsequently decreasing the hyper-thrombotic state seen in the GBM tumor microenvironment. Our observations suggest that glioma cells execute a cell intrinsic coagulation mechanism to contribute to the hyper-thrombotic tumor-microenvironment seen in GBM and may shed light onto mechanisms of cancer associated thrombosis in not only GBM, but also other malignancies.

Citation Format: George Bukenya, Anthony Sloan, Craig Horbinski, Anirban Sen Gupta, Scott Cameron, Justin Lathia. Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth [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 C080.
Abstract C085: Somatic mutational profiles of breast tumors from Hispanic/Latino women
Authors: Ding Yuan Chun , Tao Shu , Mao Allen , Ziv Elad , Neuhausen Susan L.
Published: September 2024

Background: Breast cancer is the leading cause of cancer mortality among Hispanic/Latina (H/L) women. Precision medicine holds promise for more effective treatments by targeting therapies based on somatic mutations, copy number changes, mutational signatures, and/or germline risk variants. However, there is a paucity of genomics data for H/L women with breast cancer leading to a disparity in the application of precision medicine. We have previously characterized mutational profiles of 146 breast tumors from 140 H/L women. Here, we analyze data from whole exome tumor/normal sequencing and tumor RNA sequencing from 430 self-reported H/L breast cancer cases and compare their profiles to 385 tumors from self-reported White breast cancer cases. Methods: All participants were treated at City of Hope and all sequencing data were generated using Ashion GEM ExTra (Exact Sciences). Tumor/germline sequence data were aligned to the human genome (Build37) and variants were called using the FreeBayes workflow. To determine significantly mutated genes, we used MutSigCV and dNdS. We used Fisher’s exact test to determine if the frequency of somatic mutations was significantly different among H/L women and White women and corrected for multiple hypothesis testing using Benjamini-Hochberg false discovery rate (FDR). Results: Seventeen genes and 19 genes had q-values < 0.05 in H/L and White samples, respectively. Of those, AKT1, CBFB, FOXA1, MAP2K4, MAP3K1, MLL3, PIK3CA, PTEN, RB1, RUNX1, TBX3, TP53, and ZFPM1 were significantly mutated in both. CTCF and HS6ST1 were significantly mutated only in tumors from H/L. ARID1A, CDKN1B, NCOR1, and PRRT2 were significantly mutated only in tumors from White women. There was a significantly higher frequency of TP53 mutations (FDR q-value = 0.007) and CTCF mutations (FDR q-value = 0.057) in tumors from H/L compared to tumors from Whites. Conclusions: We found TP53 and CTCF to be more commonly mutated in tumors from H/L women. CTCF mutations are seen in other tumor types, but our study is the first to demonstrate that this gene is significantly mutated in breast cancer in any population. Since CTCF is a broadly active transcriptional regulator, tumors with these mutations may be associated with broad dysregulation of gene expression.

Citation Format: Yuan Chun Ding, Shu Tao, Allen Mao, Elad Ziv, Susan L. Neuhausen. Somatic mutational profiles of breast tumors from Hispanic/Latino women [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 C085.
Abstract C095: Molecular characterization of gastric adenocarcinoma from Latinos shows homologous recombination deficiency
Authors: Montoya Dennis J , Estrada-Florez Ana , Lott Paul , Chiu Katherine , Suarez-Olaya John , Castro Fabian , Echeverry de Polanco Magdalena , Torres Javier , Bohorquez Mabel , Carvajal-Carmona Luis
Published: September 2024

Latinos have a higher risk of developing gastric cancer (GC) than non-Latino Whites (NLW). Multiple studies have shown increased treatment resistance in diffuse-type cancers, which are more prevalent in Latino patients and dominated by the genomically stable (GS) genomic subtype. However, there is little genomic data from Latino gastric tumors due to the few studies targeting this minority population. Here, we attempt to rectify the disparity of genomic data by performing whole exome and/or low-coverage whole genome sequencing on tumors from 195 Latino gastric adenocarcinoma patients, from Colombia and Mexico. We also analyze 42 Latino patients from the US from a previous study. In total, we analyze tumors from 237 patients, the largest cohort of Latino gastric cancer tumors comprehensively sequenced thus far. Molecular subtyping of our cohort shows a higher proportion of tumors with a genomically stable (GS) subtype, 59%, and less with chromosomal instability (CIN), 24%, than reported in non-Latino patients from the Cancer Genome Atlas (20% and 50% respectively). Our earlier study of germline variants from Latinos, indicated a potential enrichment of variant related to homologous recombination deficiency (HRD), an important DNA repair mechanism. Focusing on this pathway, we performed HRD scoring and show that CIN tumors had the highest HRD score compared to all other subtypes. An alternative method analyzing somatic mutational patterns identified an indel mutational signature (ID6), also related to HRD, was enriched in GS tumors. Overall, these data provide a broader picture of the genomic landscape of Hispanic tumors, highlighting HRD targeting drugs as a potential treatment for both GS diffuse-types cancers particularly seen in Latinos and CIN tumors found more generally in gastric cancer.

Citation Format: Dennis J Montoya, Ana Estrada-Florez, Paul Lott, Katherine Chiu, John Suarez-Olaya, Fabian Castro, Magdalena Echeverry de Polanco, Javier Torres, Mabel Bohorquez, Luis Carvajal-Carmona. Molecular characterization of gastric adenocarcinoma from Latinos shows homologous recombination deficiency [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 C095.
Abstract C105: Novel cancer-specific hypoxia signature predicts poor prognosis and highlights racial disparities in breast cancer
Authors: Schechter Kent , Nguyen Long C. , Yerradoddi Geetha P. , Bassiouni Rania , Carpten John D. , Rosner Marsha R.
Published: September 2024

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC displays exceptional transcriptional heterogeneity, both between patients and intratumorally, and disproportionately affects underserved women. Hypoxia, a state of low oxygen levels, is often present in the solid tumor microenvironment. In TNBC, hypoxia is a key driver of aggressiveness and therapeutic resistance. Past bulk RNA sequencing (RNAseq) studies in cancer research have lacked spatial resolution, failing to uncover precise transcriptional differences within tumor regions. This spatial limitation has been especially problematic for studying transcriptional heterogeneity of the cellular hypoxia response within tumors. By integrating single-cell RNA sequencing and spatial transcriptomic analyses in a TNBC xenograft tumor model, our research has uncovered a novel hypoxia gene signature, specific to cancer cells. Elevated expression of this hypoxia signature predicts poorer prognosis in breast cancer patients, especially within TNBC patients and those of African ancestry. This suggests that hypoxia may play a role in the racial disparities observed in TNBC prognosis, potentially informing treatment strategies. This workflow introduces a novel framework for translating general spatial transcriptomics data into clinically relevant and accurate gene signatures.

Citation Format: Kent Schechter, Long C. Nguyen, Geetha P. Yerradoddi, Rania Bassiouni, John D. Carpten, Marsha R. Rosner. Novel cancer-specific hypoxia signature predicts poor prognosis and highlights racial disparities in breast cancer [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 C105.
Abstract C107: Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients
Authors: Watts Tammara L. , Gonzalez Katerine , Shen Xiangfeng , Rogers Layne , Osazuwa-Peters Nosa , Jefferson Gina D. , Clement Cecilia G. , Range Danielle , Kahmke Russel R. , Lee Walter T. , Rocke Daniel J. , Cannon Trinitia Y. , Mowery Yvonne , Owzar Kouros
Published: September 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR004) of the Conference Program/Proceedings. Cell, Molecular, and Tumor Biology: Cell Growth Signaling Pathways

Citation Format: Tammara L. Watts, Katerine Gonzalez, Xiangfeng Shen, Layne Rogers, Nosa Osazuwa-Peters, Gina D. Jefferson, Cecilia G. Clement, Danielle Range, Russel R. Kahmke, Walter T. Lee, Daniel J. Rocke, Trinitia Y. Cannon, Yvonne Mowery, Kouros Owzar. Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients [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 C107.
Abstract C118: Modulation of Prostate Cancer Microenvironment and Immune Responses by SPDEF
Authors: Vatanmakanian Mousa K. , Sanchez-Pino Maria , Zhang Guanyi K. , Koul Sweaty , Puttalingaiah Ramesh T. , Dean Mathew , Wyczechowska Dorota K. , Ochoa Augusto , Koul Hari K
Published: September 2024

Introduction: The prostate cancer (PCa) microenvironment plays a pivotal role in modulating immune responses, potentially impacting disease progression and treatment outcomes. SPDEF, a transcription factor, has been implicated in PCa progression, yet its influence on the tumor immune microenvironment remains incompletely understood. Methods: To comprehensively evaluate the impact of SPDEF-mediated changes in the PCa microenvironment on immune cells, we employed multiple experimental approaches. Firstly, utilizing the ProcartaPlex Human Cytokine & Chemokine Panel 1 16plex assay, we analyzed cytokine and chemokine alterations in cell culture supernatants from various PCa cell line models—PC3-VC, PC3-SPDEF, RC77/T-VC, RC77/T-SPDEF, LNCaP-VC, and LNCaP-shSPDEF. Subsequently, human primary T cells were exposed to PCa cell-derived conditioned media to assess their proliferation and activation status, using IncuCyte cell imaging and flow cytometry, respectively. Results: Our ProcartaPlex assay validated transcriptomic observations from RNA-seq experiment, confirming elevated cytokine/chemokine levels in SPDEF-overexpressing models and decreased levels in SPDEF-suppressed conditions. Notably, T cell proliferation assays demonstrated increased proliferation in response to SPDEF-overexpressing PCa conditional media and diminished proliferation in SPDEF-suppressed conditions. Moreover, SPDEF downregulation led to decreased proliferation in both CD4+ and CD8+ T cells. Assessing CD8+ T cell activation markers revealed varying impacts on IFN-γ expression, showing reduced levels in LNCaP-shSPDEF but inconclusive effects in PC3-SPDEF overexpression models. Conclusions: These findings highlight the complex interplay between SPDEF alterations in the PCa microenvironment and immune cell behavior, particularly T cell proliferation and activation. The observed effects underscore the complexity of SPDEF-mediated alterations on immune responses within the tumor milieu. Further investigations into the divergent effects of SPDEF on T cell dynamics are warranted to elucidate the precise mechanisms governing these interactions, potentially offering insights into novel therapeutic targets for PCa.

Citation Format: Mousa K. Vatanmakanian, Maria Sanchez-Pino, Guanyi K. Zhang, Sweaty Koul, Ramesh T. Puttalingaiah, Mathew Dean, Dorota K. Wyczechowska, Augusto Ochoa, Hari K Koul. Modulation of Prostate Cancer Microenvironment and Immune Responses by SPDEF [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 C118.
Abstract C121: Racial differences in expression of the oxygen-sensor BACH1 in breast cancer
Authors: Nguyen Long C. , Dann Christopher , Yang Dongbo , Henn Madeline , Shi Emily , Li Thomas , Schechter Kent , Stock Letícia , Liu Wenchao , Matossian Margarite , Valdespino Andrea , Han Yoo Jane , Zhang Jing , Yerradoddi Geetha Priyanka , Li Yan , Matsumoto Mitsuyo , Olopade Olufunmilayo I , Igarashi Kazuhiko , Rosner Marsha R
Published: September 2024

Hypoxia is an important hallmark of aggressive solid tumors and a key driver of metastasis and resistance to therapy. Hypoxic stress induces the activation of various factors, such as hypoxia- inducible factors (HIFs), which facilitate cellular adaptation and promote tumorigenesis. Given the complexity of this mechanism, identifying novel targets that sensitize hypoxic tumors to therapy could have significant clinical impact. We demonstrate HIF-independent induction of BACH1 within multiple TNBC (Triple-Negative Breast Cancer) cell lines and patient-derived organoids under hypoxic conditions. Utilizing ChIP-seq, bulk, single-cell and spatial transcriptomics across diverse BACH1 knockout tumor models, our study revealed that BACH1 selectively and directly modulates the transcriptional response associated with hypoxia and stress in TNBC. TGCA analysis reveals racial disparities in BACH1 mRNA expression in TNBC BACH1 mRNA and activity across all breast cancer subtypes (Basal, Her, LumA, LumB). Our findings suggest that BACH1 is an oxygen-sensitive mediator of hypoxia and a promising therapeutic target for mitigating hypoxia-induced pro-metastatic signaling and treatment resistance. These results also highlight the necessity of accounting for racial differences in BACH1 expression and function as a means of developing targeted therapy that takes into account racial disparities in TNBC.

Citation Format: Long C. Nguyen, Christopher Dann, Dongbo Yang, Madeline Henn, Emily Shi, Thomas Li, Kent Schechter, Letícia Stock, Wenchao Liu, Margarite Matossian, Andrea Valdespino, Yoo Jane Han, Jing Zhang, Geetha Priyanka Yerradoddi, Yan Li, Mitsuyo Matsumoto, Olufunmilayo I Olopade, Kazuhiko Igarashi, Marsha R Rosner. Racial differences in expression of the oxygen-sensor BACH1 in breast cancer [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 C121.
Abstract C137: Exploring cardiotoxicity risk factors among patients diagnosed with breast cancer
Authors: Schiaffino Melody K , Nguyen Van "Vannie" K. , Rash Dominique , Fernandez Alicia
Published: September 2024

Introduction Heart disease is the second most common cause of death for cancer survivors after their cancer diagnosis. Patients diagnosed with cancer, especially those with left-side breast cancer are at higher risk for treatment related toxicity. This burden is exacerbated for vulnerable patients that experience structural and chronic risk factors such as language barriers and disability which contribute to poorer survival. This study compared multi-level factors and their effect on age of diagnosis. Methods We explored a diverse population of N=1795 patient electronic medical records for patients diagnosed with left-side breast cancer and compared characteristics of patients by age, race, ethnicity, history of heart disease, disability status. Descriptive and Kruskal-Wallis ANOVA models were used to compare groups. Results The mostly female cohort of language diverse patients had an average of 66 years, most were White (64.5%), retired (52.1%), and on Medicare (43.2%). Approximately 17.8% were Latine and 13.3% needed an interpreter. Disability status was 9.7% and 8.8% had a history of heart disease. Patients diagnosed with breast cancer who were disabled were younger compared to those without a disability (60 yrs vs 67, p<.0001). When we compared language proficiency, we found this difference persisted as patients with a disability and were limited English were younger compared to patients that experienced neither (61yrs vs 67, p<.0001). Discussion This exploratory analysis is one of the first to explore the role of disability among minoritized and limited English proficient patients with breast cancer. More research is necessary to understand how to best plan and support diverse and disabled patients diagnosed with cancer to minimize their risk and improve outcomes.

Citation Format: Melody K Schiaffino, Van "Vannie" K. Nguyen, Dominique Rash, Alicia Fernandez. Exploring cardiotoxicity risk factors among patients diagnosed with breast cancer [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 C137.
Abstract C155: Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors
Authors: Fwelo Pierre , Adekunle Toluwani E. , Adekunle Tiwaladeoluwa B. , Garza Ella R. , Huang Emily S. , Lawrence Wayne R. , Ewing Aldenise P.
Published: September 2024

Introduction: Non-Hispanic Black colorectal cancer (CRC) patients have a higher risk of mortality compared to most other racial/ethnic groups. Limited studies examine the contribution of socioeconomic (SES), clinicopathologic, or treatment variations toward mortality disparities. This retrospective cohort investigation examined the extent to which SES, clinicopathologic, and treatment factors explain racial/ethnic differences in CRC mortality. Methods: We studied 146,515 individuals ,18+ years old, with a confirmed diagnosis of CRC within 2010-2017 identified from the Surveillance, Epidemiology, and End Results (SEER) database. We performed Cox regression analyses to examine the association of race/ethnicity, surgery type, and tumor site with all-cause mortality and CRC-specific mortality. We then performed mediation analysis to quantify the extent to which mortality differences were mediated by SES, clinicopathologic, and treatment factors. Results: Non-Hispanic Black patients had a significantly higher hazard of all-cause mortality than non-Hispanic White patients. The non- Hispanic White versus non-Hispanic Black patients’ comparison demonstrated that variations in SES and clinicopathologic factors significantly explained 46.63% (indirect effect HR: 0.92, 95% CI 0.91-0.93) and 10.87% (indirect effect HR: 0.98, 95% CI 0.97-99) of the excess all-cause mortality among non-Hispanic Black patients, respectively. The Hispanic vs. non-Hispanic Black comparisons identified SES as the most influential mediator, explaining 19.68% of the excess all-cause mortality. The proportions mediating for CRC-specific mortality showed comparable outcomes to all-cause mortality. Conclusions Non-Hispanic Black patients had greater risk for all-cause mortality and CRC-specific mortality attributed to SES and clinicopathologic variations compared to other racial/ethnic groups. Future studies should investigate equity in healthcare through interventions addressing SES-related disparities.

Citation Format: Pierre Fwelo, Toluwani E. Adekunle, Tiwaladeoluwa B. Adekunle, Ella R. Garza, Emily S. Huang, Wayne R. Lawrence, Aldenise P. Ewing. Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors [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 C155.
Abstract C158: Contribution of multi-organ cancer predisposition genes for gastric cancer risk of different histological subtypes
Authors: Estrada-Florez Ana P. , Lott Paul C. , Carvajal Carmona Luis G.
Published: September 2024

Approximately 10% of gastric cancer (GC) cases exhibit familial clustering, yet only 1-3% can be explained by known hereditary syndromes, being Hereditary Diffuse Gastric Cancer (HDGC) the most well-established disease predisposing for diffuse gastric cancer. Familial intestinal gastric cancer (FIGC) has been defined clinically, but it remains mostly genetically unexplained. Likewise, the heritability of mixed GC remains to be uncovered. We aimed to estimate the frequency of known cancer predisposition gene variants in GC cases with family history of cancer and/or early onset. We evaluated the contribution of pathogenic and likely pathogenic (P/LP) variants in well-established and multi-organ cancer predisposition genes for GC risk in a large multi-center study involving 750 GC patients, either by targeted sequencing or whole exome sequencing. We identified 45 patients (6%) with P/LP variants in ATM (17 cases), BRCA2 (10 cases), MLH1 (five cases), TP53 (three cases), BRCA1, PALB2, RAD51D and CHEK2 (two patients each), and RAD51C and PMS2 (one case each), all mutually exclusive. The P/LP variant prevalence was higher in intestinal (9.8%) than in diffuse (4.3%) or mixed GC (4.5%) (p-value=0.023), with no clear difference per mutated gene by histological subtypes. Only sixteen of the 45 variant carriers fulfilled the criteria for genetic testing of at least one cancer predisposition syndrome. Our findings indicate that multi- organ cancer predisposition genes should be included in gene panels used for investigating germline variants in GC patients, especially when there is family history of cancer but irrespective of histology subtype, as this would increase the chance of identifying patients that might benefit from prevention and targeted treatment strategies.

Citation Format: Ana P. Estrada-Florez, Paul C. Lott, Luis G. Carvajal Carmona. Contribution of multi-organ cancer predisposition genes for gastric cancer risk of different histological subtypes [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 C158.
Abstract PR016: Do U.S. quitsites present information related to providing services for LGBTQ individuals? An audit study
Authors: Ramos Santiago Jeffrey Wilmer , McIntosh Scott , Orfin Rafael , Lara Daimarelys , Joseph Skylar , Kaur Manpreet , Ramos-Pibernus Alixida , Cupertino Ana Paula , Ossip Deborah , Cartujano-Barrera Francisco
Published: September 2024

Introduction: Most U.S. quitlines have quitsites, websites designated to promote their services. However, little is known about the design of the quitsites and if they present information relevant to providing services for LGBTQ individuals. The present study audited quitsites for the presence of information regarding services for LGBTQ individuals. Methods Using an audit checklist consisting of nine criteria, a cross-sectional audit of the U.S. quitsites was conducted between October 16th, 2023, and November 8th, 2023. The audit was divided into two phases: 1) auditors evaluated each quitsite separately, and 2) auditors met to discuss points of disagreement and reach a consensus. The interrater agreement was calculated. Frequencies and percentages were calculated for each criterion. Results The audit evaluated a total of 46 quitsites. Auditors had an interrater agreement of 96.85%. Findings indicated that most quitsites had at least a singular mention of the LGBTQ community somewhere on their website (84.8%). However, only 4.3% of the quitsites mentioned the LGBTQ community on their landing page. Conclusions It is recommended that quitsites explicitly mention services for LGBTQ individuals on their landing page, which has the potential to engage the community into quitline services and reduce tobacco-related disparities. Implications This study represents the first audit to assess whether U.S. quitsites present information relevant to providing services for LGBTQ individuals. This research adds knowledge about how official quitline websites address services for the LGBTQ community. The results suggest that quitsites explicitly mention the provision of services for LGBTQ individuals on their landing page, which has the potential to engage LGBTQ individuals into quitline services and reduce tobacco-related disparities.

Citation Format: Jeffrey Wilmer Ramos Santiago, Scott McIntosh, Rafael Orfin, Daimarelys Lara, Skylar Joseph, Manpreet Kaur, Alixida Ramos-Pibernus, Ana Paula Cupertino, Deborah Ossip, Francisco Cartujano-Barrera. Do U.S. quitsites present information related to providing services for LGBTQ individuals? An audit study [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 PR016.
Receiving a Pathogenic Variant in a Population Breast Cancer Screening Trial: A Mixed Method Study
Authors: Riddle Leslie , James Jennifer Elyse , Naeim Arash , Madlensky Lisa , Brain Susie , DeRosa Diana , Eklund Martin , Fiscalini Allison Stover , Heditsian Diane , Koenig Barbara , Ross Katherine , Sabacan Leah P. , Tong Barry , Wenger Neil , Joseph Galen
Published: September 2024

Introduction: Risk-based breast cancer screening aims to address persistent high morbidity and mortality. This study examined the experience of participants in the Women Informed to Screen Depending on Measures of Risk (WISDOM) trial who received a pathogenic variant in one of nine high or moderate penetrance breast cancer genes. Methods: Participants completed a brief survey (n = 181) immediately following the results disclosure and 1 year later. Descriptive statistics were computed and comparisons between participants at different risk levels were performed using Fisher’s exact and McNemar’s tests. Analysis of qualitative interviews (n = 42) at 2–4 weeks and 6 months post-results disclosure compared responses at the 2 time points and explained and elaborated on the survey data. Results: 66.3% of survey respondents felt very or moderately prepared to receive genomic results. At the T1 survey, 80.7% of participants had shared the genetic result with a blood relative, increasing to 88.4% at T2; providing information and encouraging cascade testing were the most common reasons for sharing. Communication with a blood relative, other healthcare providers beyond the primary care provider, and cascade testing were higher for participants with a high risk than low or moderate risk genomic finding. Qualitative interviews elucidated varied reasons why participants felt (un)prepared for the results, including whether or not they had a family history of breast cancer, and illustrated the complexity of decision-making about sharing results. Conclusions: Although most participants communicated results with family members and healthcare providers in accordance with their risk level, questions remain about how to adequately prepare individuals to receive pathogenic results, ensure timely and accessible follow-up care, and facilitate genetic counseling and cascade testing of at-risk relatives in the setting of population risk-based screening.
Comparison of Tissue and Urine Microbiota in Male, Intervention Naive Patients with and without Non-Invasive Bladder Cancer
Authors: Ozer Muhammed S. , Incir Canet , Yildiz Huseyin A. , Deger Muslim D. , Sarikaya Alper E. , Tuncok Yesim , Ergor Gul , Esen Nuran , Sen Volkan , Bozkurt Ozan , Esen Adil
Published: September 2024

Introduction: To investigate the presence of dysbiosis in patients with naive bladder cancer. Methods: Twelve male patients with non-invasive bladder cancer and twelve age-matched healthy males had midstream urine and tissue samples taken. A history of endourological interventions was determined as an exclusion criterion, ensuring that the study was designed solely with naïve participants. The bacterial 16s ribosomal RNA V3-V4 regions were used to examine urine and tissue samples. We compared the microbiota composition of the bladder cancer and control groups. Results: Escherichia Shigella (p < 0.001), Staphylococcus (p < 0.001), Delftia (p < 0.001), Acinetobacter (p < 0.001), Corynebacterium (p < 0.001), and Enhydrobacter (p < 0.001) were abundant in bladder cancer tissue samples. Escherichia Shigella (p < 0.001), Ureaplasma (p < 0.001), Lactobacillus (p = 0.005), Stenotrophomonas (p < 0.001), Streptococcus (p < 0.001), Corynebacterium (p < 0.001), and Prevotella (p = 0.039) were abundant in bladder cancer urine samples. Midstream urine has a sensitivity of 83% for detecting dysbiotic bacteria in cancer tissue. Conclusions: Our research is the first microbiota study of bladder cancer done with naive patients who have never had an endourological intervention. Escherichia Shigella, Staphylococcus, Acinetobacter, Enhydrobacter, Delftia, Corynebacterium, and Pseudomonas were detected as dysbiotic bacteria in bladder cancer. The sensitivity of the midstream urine sample in detecting dysbiosis in tissue is 83%.
Plasma Cytokines Pattern as a Prognostic Marker for Esophageal Squamous Cell Carcinoma via Unsupervised Clustering Analyses
Authors: Chuang Cheng-Hsun , Huang Pei-Ming , Liang Sung-Tzu , Chen Ke-Cheng , Lin Mong-Wei , Kuo Shuenn-Wen , Liao Hsien-Chi , Lee Jang-Ming
Published: September 2024

Introduction: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed. Results: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines. Conclusions: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.
Demographic Trends, Co-Alterations, and Imatinib Resistance across Genomic Variants in Gastrointestinal Stromal Tumors: An AACR Project GENIE Analysis
Authors: Stecko Hunter , Iyer Sidharth , Tsilimigras Diamantis , Pawlik Timothy M.
Published: September 2024

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract, the treatment of which represents a significant breakthrough in targeted cancer therapy. Given its overall rare nature, genomic differences and clinical implications between demographic groups have not been previously investigated. Methods: Anonymized demographic, clinical, and genomic data from 1,559 GIST patients in the American Association for Cancer Research Project GENIE database were analyzed using cBioPortal and custom Python scripts. Data on patient demographics, genomic alterations, and co-occurrence genetic alerations were collected and classified according to clinical implications using the OncoKB database. χ2 tests for differences in genomic alterations were used across various demographic factors and mutual exclusivity analysis was employed to identify co-mutation patterns. Results: Male patients demonstrated higher incidence of PDGFRA mutation (14.56% vs. 8.05%; p < 0.001), while female patients had higher likelihood of NF1 mutations (7.46% vs. 3.23%; p = 0.001). Asian patients had higher alteration rates at KIT (85.59%; p = 0.002). Co-occurrence analysis revealed KIT alterations frequently co-occurred with CDKN2A (q < 0.001), MTAP (q = 0.045), and PTEN (q = 0.056), while there was mutual exclusivity with PDGFRA (q < 0.001), NF1 (q < 0.001), and BRAF (q = 0.015). CDKN2A alterations co-occurred with MTAP (q < 0.001) and PIK3CA (q = 0.015), while being mutually exclusive with TP53 (q = 0.002) and NF1 (q = 0.007). Trends were similar among patients who had received no prior medical treatment. Imatinib-resistant mutations were more common among male patients (25.6% vs. 18.9%; p = 0.0056) and individuals under 55 (27.3% vs. 20.9%; p = 0.0228). Among patients with imatinib-resistant mutations, 77.78% had sunitinib resistance, while 70.25% maintained sensitivity to ripretinib. Conclusion: Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.
Increased Intrauterine Transfusion Blood Volume Needed to Correct Fetal Anemia due to Placental Chorioangioma
Authors: Hamzeh Catherine , Green Jessica , Hamadeh Grace , Korst Lisa M. , Chmait Ramen H.
Published: September 2024

Introduction: To compare the blood volume transfused for fetal anemia in cases of placental chorioangioma versus red blood cell (RBC) alloimmunization in patients matched for gestational age (GA) and hydrops. Methods: Study patients had intrauterine transfusions and were obtained from 3 sources: group (1) placental chorioangioma patients treated at our center (2016–2023); group (2) placental chorioangioma patients reported in the medical literature; and group (3) RBC alloimmunization patients treated for fetal anemia at our center (2016–2023) matched (2:1) to patients in groups 1 and 2 by GA at procedure and presence of hydrops. The expected volume (cc) of transfusion was calculated for all patients based on a formula commonly used for fetal anemia in cases of RBC alloimmunization that includes the GA at procedure, pre-transfusion hemoglobin, donor hemoglobin, and target hemoglobin. The ratio of the volume actually transfused to the expected volume was calculated for each group and for groups 1 and 2 combined; comparisons were made using nonparametric testing. Results: By group, the patients studied included: (1) 7 treated chorioangioma patients, (2) 8 chorioangioma patients described in the literature, and (3) 30 matched RBC alloimmunization patients. The median (range) GA at procedure for groups 1, 2, and 3 was 29.6 (22.7–32.7), 27.0 (24.0–30.0), 28.4 (22.7–34.3) weeks. The median pre-procedure hemoglobin for each group was 8.5 (5.8–12.5), 6.7 (5.6–12.0), and 5.3 (2.2–10.7) g/dL, and the median post-procedure hemoglobin for each group was 12.9 (11.5–14.0), 12.7 (9.6–14.7), and 13.6 (8.0–15.7) g/dL. The median (range) ratio of the actual to the expected volume transfused for each group was 2.50 (1.79–8.33), 1.64 (1.11–3.85), and 1.10 (0.69–1.86) (p < 0.001). When groups 1 and 2 were combined, the median ratio was 1.89 (1.11–8.33), which remained statistically significant when compared to group 3 (p < 0.001). Conclusion: Intrauterine transfusion for fetal anemia in cases of large placental chorioangiomas appeared to require nearly twice the blood volume that was normally anticipated for cases of RBC alloimmunization, although the actual amount transfused varied widely.
Animal Protection Officers: Professional Identity, Professional Stressors, and Mental Health Needs
Authors: Meyer Laura , Brown Courtney , Nikitina Katia , Ettinger Daniel
Published: September 2024

Animal protection officers (APOs) fulfill critical community roles but are underrepresented in academic literature. This study explored APOs’ professional identities, professional stressors, positive job aspects, and mental health needs and access. Our mixed-methods design featured a survey followed by interviews. The survey was disseminated to APOs from four local agencies. Results from 18 respondents revealed that seeing a child injured by an animal or an animal injured by a human were the most stressful work situations. Positive job aspects included helping animals, public education, and supporting community safety. Only four respondents had accessed mental health services for job-related issues. Nine respondent interviews yielded themes addressing how APOs make meaning, stressors and resilience factors, and mental health supports. Recommendations based on survey and interview responses are provided.
Under the skin: Portraits by Abraham de Vries (c. 1590-1649/50) recognised and revealed
Authors: van de Puttelaar Carla , Meijer Fred G.
Published: September 2024

This article discusses four portraits by Abraham de Vries (c. 1590-1649/50), three of which were recently recognised as the artist’s work, and all of which were subject to changes over time. The appearance of these portraits, as the authors came across them, prompted further investigation.

The first two are portraits of the same girl (figs. 1a and 2a) from c. 1629 that originally had virtually the same appearance, as technical research has revealed. The first was reduced in size, the second was overpainted substantially, particularly in the costume.

A portrait of a bearded man (fig. 11a) had been sold as a portrait of a rabbi by Simon Kick, but technical examination revealed that it was initially painted as a portrait of the French garden designer Jacques Boyceau, signed in monogram by De Vries and dated 1629 under a layer of overpaint. The original appearance of the portrait is known through a contemporary print (fig. 14). Interestingly, later changes appear to have been executed by De Vries himself, but the circumstances remain unclear. Additionally, a signed portrait of an unidentified sitter, also from 1629 and now in the Petit Palais in Paris (fig. 12a), had received a different collar at some point in its history, which was cleaned off before its acquisition by the museum.

Similarities in handling and execution with other portraits by Abraham de Vries, for instance in the hair, collars and eyes, prove his authorship of the four portraits that are the focus of this article. They enrich the painter’s oeuvre and further confirm his excellent abilities as a portraitist in the first half of the seventeenth century.
Jesuits, Jansenists, and the Culture Wars
Authors: Stróżyński Mateusz
Published: September 2024

This introductory article explores the relevance of studying the Jesuit-Jansenist conflict in early modern France against the broader background of modernity as such and its inherent problems with fragmentation, isolation, and polarization in all areas of culture. It begins with a reference to the particular use of the study of early modernity and its religious and sociopolitical problems by the two prominent dissidents of the twentieth century, Leszek Kołakowski (1927–2009) and Jan Patočka (1907–77), in order to draw some potential parallels between the contemporary “culture wars” and the conflict between the Jesuits and the Jansenists. The contributions, stemming from a conference held at Adam Mickiewicz University in Poznań in March 2023, celebrating the four-hundredth anniversary of the birth of Blaise Pascal, shed light on various aspects of classical culture, education, tradition, and innovation in the areas of theatre, music, and philosophy in seventeenth-century France.
Seneca, Corneille, and the Ghost of Jesuit Classicism
Authors: Boparai Jaspreet Singh
Published: September 2024

The precise effects of Jesuit education can be difficult to discern in a given writer or artist. Little is known about Pierre Corneille’s (1605–84) humanist formation at the Jesuit college in Rouen; like his philosophical orientation, its nature must be extrapolated from scanty, equivocal evidence. This article traces Corneille’s reception of Seneca (c.4 bce–65 ce) in his early tragedy Médée and his heroic drama Cinna in an attempt to come to grips with his idiosyncratic classicism, which diverges considerably from contemporary Aristotelianism. Corneille is a practical man of the theatre and focuses less on Aristotle than on Seneca’s philosophical prose, as well as his tragedies. By the time he comes to compose Rodogune, Corneille has absorbed Seneca so completely that it seems almost impossible to articulate precisely how his work is “Senecan,” except to point to Seneca’s shadow. Perhaps Jesuit classicism is easier to study in a less idiosyncratic writer like Thomas Corneille (1625–1709)?
The French Leçons de Ténèbres and the Foundation of the Jansenist Music Criticism
Authors: Favier Thierry
Published: September 2024

The spread of the Leçons de ténèbres in the French capital and later in large provincial cities contributed to the evolution of musical practices and the listeners’ sensibilities and favored the incorporation of religious music into secular musical calendars. This explains why, from the end of the seventeenth century, the genre has been the focus of criticism from clerics and lay people of different persuasions, who denounced the contamination of the church by opera, using the conventional argument of antitheatricality. Initially focused on the Lessons, the criticism’s terms and arguments used against the Lessons became instrumental in the Jansenist’s critique of modern music throughout the eighteenth century, particularly to contest Jesuit musical patronage and Jesuits’ sensualist conception of music for religious services. While Jansenist criticism portrays an irreducible opposition between opponents and supporters of modern music, the latter being equated with the Jesuits, the article highlights the ambiguities of Jansenist positions. An analysis of these criticisms reveals a double reference to the Augustinian tradition, on the one hand concerning the opposition between musica luxuriantis and musica sapientis and, on the other, a moral reflection on musical pleasure’s legitimacy based on individual introspection. In the second half of the eighteenth century, the condemnation of all modern forms of religious music appeared to contradict the claim to a part of this Augustinian heritage.
Range shifts and non-monotonic clines in studies of Bergmann’s rule as applied to climate change
Authors: Shelomi Matan
Published: September 2024

Bergmann’s rule states that organisms should be smaller in warmer climates. This traditionally implied warmer latitudes, but also applies to warmer eras, as forming due to climate change. Integrating spatial and temporal ecology (chronoecogeography) can help us understand and predict how different species respond to environmental changes over time. However, study results can be misinterpreted if researchers do not take steps in the data collection or analysis stages to account for range shifting or non-monotonic patterns. Multiple variables can cause an organism’s geographic and recent temporal size clines to differ significantly, as seen in a review in this article, and these cannot easily be modeled. Range shifting can affect Bergmann’s rule modeling, especially regarding effects from climate change, and this article suggests methods to account for this when incorporating the dimension of time into climate change-focused ecogeographic research.