bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6242: A workflow execution system in a data fabric for integrative cancer analyses
Authors: Venkat Aarti , Ribeyre Pauline , Qureshi Jawad , Narumanchi Sai Shanmukha , Maxwell J Montgomery , Winslow Bill , Garcia Sara Volk , Meyer Chris , Garcia Tzintzuni , Vassilatos Peter , Malson Clinton , Zhang Zhenyu , Grossman Robert 
Published: March 2024

Abstract
Cancer researchers are increasingly conducting multi-omic research and performing integrative analyses on combinations of genomic, proteomic, transcriptomic, imaging, single cell and other data modalities. However, it is quite challenging for a researcher to effectively access, aggregate and analyze data and metadata from different data sources in a scalable and reproducible manner, as the individual datasets may be disconnected from each other, and have separate authentication and authorization requirements. We developed a workflow execution system in a data fabric called the Biomedical Research Hub (BRH) to overcome these challenges for academic researchers. The BRH is powered by the Gen3 technology, an open-source Kubernetes based software stack that allows cancer researchers to create their own data fabric and interoperate with data from multiple data sources. The workflow execution system utilizes nextflow and allows researchers to run containerized applications in the cloud in a secure and isolated environment. Data from multiple resources can be combined for analysis using convenient pay models including NIH STRIDES. We plan to demonstrate the application of our system on a scientific use case involving Clonal Hematopoiesis of Indeterminate potential (CHIP), a phenomenon that has been associated with aging, cancer, cardiovascular diseases, infection and all-cause mortality. We run containerized CHIP workflows on the cloud, utilizing two datasets accessible through BRH: i) The Genomic Data Commons, the world’s largest source of harmonized cancer data and ii) BioDataCatalyst, an NHLBI ecosystem that drives discovery and innovation for heart, lung, blood and sleep disorders. Our system is ideally suited for machine learning on large aggregated cancer datasets and federated learning tasks.
Citation Format: Aarti Venkat, Pauline Ribeyre, Jawad Qureshi, Sai Shanmukha Narumanchi, J Montgomery Maxwell, Bill Winslow, Sara Volk Garcia, Chris Meyer, Tzintzuni Garcia, Peter Vassilatos, Clinton Malson, Zhenyu Zhang, Robert Grossman. A workflow execution system in a data fabric for integrative cancer analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6242.
Abstract 6278: Effect of tumor size and BRAF mutational status in Middle Eastern differentiated thyroid cancer
Authors: Bu Rong , Siraj Abdul K. , Parvathareddy Sandeep K. , Iqbal Kaleem , Azam Saud , Qadri Zeeshan , Al-Rasheed Maha , Haqawi Wael , Benito Allianah D. , Al-Kuraya Khawla S. 
Published: March 2024

Abstract
Background: Risk stratified treatment strategies have become a focus in the treatment of Differentiated Thyroid Cancer (DTC). Tumor size at diagnosis has been widely used as a major mortality risk factor in risk stratification of DTC, but whether this is generally applicable, particularly in patient with different BRAF genetic backgrounds, is unclear. The current study was designed to analyze whether tumor size at diagnosis is a major prognostic factor in Middle Eastern DTC.
Methods: We conducted a comparative study of the relationship between tumor size at diagnosis and event free survival with respect to BRAF status in 1709 consecutive patients treated surgically for Middle Eastern DTC. Patients were divided into four groups according to the size of tumor (≤4 cm vs. &gt;4 cm) and BRAF mutation status: Group 1 (≤4 cm without BRAF mutation, n = 587), Group 2 (≤4 cm with BRAF mutation, n = 765), Group 3 (&gt;4 cm without BRAF mutation, n = 198) and Group 4 (&gt;4 cm with BRAF mutation, n = 159). Predictors of event-free survival (EFS) were compared using the Log-rank test and Cox proportional hazards models.
Results: Following multivariate analysis, patients with tumors &gt;4cm did worse than patients with tumors &lt;4cm with respect to EFS (Group 3 vs Group1 HRadjusted=1.38, 95% CI=1.02-1.86, p = 0.0359; Group 4 vs Group 2 HRadjusted=1.61, 95% CI=1.20-2.16, p = 0.0017). However, patients did not differ according to EFS, regardless of the presence of BRAF mutation within each size category (Group 2 vs Group 1 HRadjusted=0.98 CI=.78-1.23, p=0.8415 ; Group 4 vs Group 3 HRadjusted=1.17, 95% CI=0.84-1.62, p=0.3523]
Conclusion: Tumor size is an independent predictor of EFS in Middle Eastern DTC patients, regardless of BRAF mutational status.
Citation Format: Rong Bu, Abdul K. Siraj, Sandeep K. Parvathareddy, Kaleem Iqbal, Saud Azam, Zeeshan Qadri, Maha Al-Rasheed, Wael Haqawi, Allianah D. Benito, Khawla S. Al-Kuraya. Effect of tumor size and BRAF mutational status in Middle Eastern differentiated thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6278.
Abstract 6280: Vitamin D enhances luminal differentiation of prostate organoids more than androgens
Authors: Cerna Oscar Fernando , Nonn Larisa , Schlicht Mike , Krieger Kirty 
Published: March 2024

Abstract
Background: Prostate Cancer (PCa) is a prevalent disease affecting over two million men worldwide. Vitamin D is a fat-soluble hormone that is well-known for its role in the maintenance of strong bones and has anti-cancer effects in prostate cancer. Vitamin D is synthesized in the skin in response to sun exposure and may be supplemented with diet. However, since melanin hinders this synthesis many African Americans are deficient in vitamin D. Vitamin D circulates as 25-hydroxyvitamin D3 (25D) and 25-dihydroxyvitamin D3 (1,25D). Hydroxylation of 25D by the kidney or within tissues forms the active hormone 1,25D. 1,25D binds the vitamin D receptor (VDR), a steroid transcription factor. Androgens are the main regulatory hormones involved in prostate growth and differentiation. Epithelial differentiation is the process in which progenitor or stem cells become specialized cells, such as basal or luminal. In the prostate, luminal epithelial cells are the most differentiated and are the origin of PCa. We used mouse prostate organoids to replicate the differentiation process in vitro and to help identify the role of 1,25D on epithelial differentiation in the presence and absence of other androgens.
Methods: Primary mouse prostate cells were isolated from dorsal lateral lobes and grown as organoids. Over two weeks, we treated these organoids with concentrations of 1,25D and androgen (dihydrotestosterone, DHT). The four treatment groups were control, 1,25D only, DHT only and 1,25D+DHT. Organoids were imaged and analyzed for number, size and phenotype. Phenotypes were identified as luminal, acinar, or solid.
Results: Luminal phenotypes were more prevalent in 1,25D conditions compared to control or DHT alone. The number, size and percent of luminal organoids was highest in 1,25D + DHT compared to all other groups. Ongoing studies include examination of prostate organoids from mice with a vitamin D-deficient diet and staining of the organoids for differentiation markers.
Conclusions/Significance: We observed that 1,25D enhanced luminal epithelial differentiation in mouse prostate organoids. These findings suggest that chronic vitamin D deficiency may increase risk of aggressive prostate cancer, due to decreased epithelial differentiation. This has implications for the disparity of aggressive PCa observed in African American men who have lower vitamin D levels compared to their white counterparts.
Citation Format: Oscar Fernando Cerna, Larisa Nonn, Mike Schlicht, Kirty Krieger. Vitamin D enhances luminal differentiation of prostate organoids more than androgens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6280.
Abstract 6284: Multimoics reveal aberrant pathways and regulation of castration resistant and metastatic prostate cancer
Authors: Horning Aaron M. , Hung Chia-Nung , Liebermann Brandon , Chou Chih-Wei , Lin Che-Kuang , Wang Yao Vickie , Jin Victor X. , Liss Michael A. , Wang Chiou-Miin , Lin Chun- , Chen Meizhen , Huang Tim H-M , Chen Chun-Liang 
Published: March 2024

Abstract
Prostate cancer is a highly heterogeneous disease and in the end, 30% of patients will experience metastatic and fatal castration resistant prostate cancer (mCRPC). In spite of the vigorous efforts to search the causes of metastatic CRPC (mCRPC), the mechanisms are still largely unresolved. To understand the progression of mCRPC, we utilized scRNA-seq to profile global expression patterns in LNCaP, LNCaP-Abl and PC3 representing castration sensitive and resistant states. ScRNA-seq revealed 335 and 2393 differentially expressed (DE) genes in early and advanced castration resistant states enriched in 43 and 163 aberrant pathways. These included focal adhesion, adherens junction, leukocyte transendothelial migration, ECM-receptor interaction, regulation of actins, gap junction, TGFb, WNT, Hippo, Ephrin and other pathways. Upregulation of these pathways predicted worst disease free/overall survival of The Cancer Genomes Atlas (TCGA) PC cohort using Kaplan-Meir estimation. Further scRNA-seq also indicated most of the pathways were also enriched in ex vivo circulating tumor cells derived from biochemical recurrent or mCRPC patients. Small molecule perturbation verified function of 9 pathways involved in cell proliferation, migration, invasion, and organoid formation of mCRPC cell lines and CTCs. We then delved into how these genes are regulated by the global chromatin landscape through Assay for Transposase-Accessible Chromatin and high throughput DNA-seq (ATAC-seq). In castration sensitive LNCaP, active chromatins are associated with genes but most of them are located in distal intergenic regions. Conversely, the majority (51.9-57.6%) of open chromatins in castration resistant PC cells are situated in promoters that lie within 1kb of transcription start sites. KEGG pathway enrichment analysis uncovered Hippo, Wnt, tight junction, adherens junction, circadian and other pathways that corroborate the scRNA-seq findings. GRO-seq data indicated that nascent transcription supports gene body transcription in castration resistant cells but leads to massive pausing in castration sensitive cells.
Citation Format: Aaron M. Horning, Chia-Nung Hung, Brandon Liebermann, Chih-Wei Chou, Che-Kuang Lin, Yao Vickie Wang, Victor X. Jin, Michael A. Liss, Chiou-Miin Wang, Chun- Lin, Meizhen Chen, Tim H-M Huang, Chun-Liang Chen. Multimoics reveal aberrant pathways and regulation of castration resistant and metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6284.
Abstract 640: In vivo rescue of p53 tumor suppressor function with ADGN-531 across Pan-p53 alterations
Authors: Divita Gilles , Grunenberger Audrey , Czuba Elodie , Josserand Veronique , Guidetti Melanie , Desai Neil 
Published: March 2024

Abstract
p53 tumor suppressor mutations result in loss of function of p53 in approximately 50% of all human cancers.TP53 missense, nonsense mutations and p53 deletion are present in about 50%, 12% and 5% of all p53 driven cancers, respectively. To date there is no effective treatment for rescuing p53 function in cancers using a pan-p53 approach. The use of ADGN-531 is a new potent strategy combining mRNA with a tumor selective peptide nanocarrier to rescue of p53 tumor suppressor function.
ADGN-531 contains proprietary p53-mRNA complexed with proprietary short amphipathic peptides in the form of nanoparticles. ADGN-531 was evaluated on 20 different cancer cell lines harboring various p53 mutations. In-vivo efficacy of IV-administered ADGN-531 nanoparticles was evaluated on colorectal SW403 (p53 nonsense/KRASG12V), osteosarcoma SaOs2 (p53 null) and NSCLC NCI-H358 (p53 null/KRASG12C) mouse xenografts at a dose of 0.25-1.0 mg/kg weekly. ADGN-531/sotorasib synergy was evaluated in vitro on NCI-H358 (p53 null/KRASG12C) and Mia-PACA (p53R48W/KRASG12C) cells and in vivo on NCI-H358 mouse xenograft. ADGN-531 markedly inhibits the growth of a large panel of cancer cells harboring p53-missense or nonsense mutations or p53-deletion, by rescuing p53 transcriptional activity and subsequent expression of its target proteins.
ADGN-531 induces cell cycle arrest in G1 due to p21 upregulation and apoptosis following BAX and PUMA activation. IV-administration of ADGN-531 resulted in dose responsive tumor growth inhibition in SaOs2, SW403 and H358 xenografts independent of KRAS status. We demonstrated a strong synergy in a NSCLC H358 xenograft (tumor regression 80%) when restoring P53 function with ADGN-531 (0.5mg/kg, weekly) along with inhibition of KRASG12C mutant using sotorasib (10mg/kg, daily). ADGN-531 potentiated the effect of sotorasib on sotorasib resistant cells harboring high level of KRASG12C in permanent active state. ADGN-531 treatments are well tolerated, no sign of clinical toxicity was detected after single or repeated administrations.
ADGN-531 is effective in rescuing p53 function both in vitro and in vivo across a wide range of p53 alterations. Our study provides a proof-of-concept that restoration of tumor suppressor function by ADGN-531 could be used as a single agent therapy in P53 altered tumors independent of other driver mutations e.g., KRAS, or with other therapies for potent combinatorial cancer treatment.
Citation Format: Gilles Divita, Audrey Grunenberger, Elodie Czuba, Veronique Josserand, Melanie Guidetti, Neil Desai. In vivo rescue of p53 tumor suppressor function with ADGN-531 across Pan-p53 alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 640.
Abstract 6417: Urinary PKM2 in muscle invasive bladder cancer
Authors: Matye David , Leak Juliann , Abbott Erika , Woolbright Benjamin , Taylor John 
Published: March 2024

Abstract
Background & Aims: Biomarkers are commonly used for both detection of cancer and monitoring response to treatment. Although several biomarkers have demonstrated promise in patients with bladder cancer (BCa), only urine cytology is widely utilized. Increased availability of effective biomarkers may improve clinical decision making and reduce the need for more invasive imaging. The M2 isoform of pyruvate kinase (PKM2) is upregulated in a number of cancers, including BCa, and promotes metabolic changes, including a shift to aerobic glycolysis. The aim of this study was to determine whether urine PKM2 levels are useful for detection and monitoring response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive BCa.
Methods: Urine samples from patients enrolled in the University of Kanas Medical Center Bladder Cancer Biorepository were analyzed for levels of PKM2. Patients were included if they had both T2 stage disease and had received cisplatin-based neoadjuvant chemotherapy and were compared to healthy controls. Patients were categorized based on their pathological response to treatment and recurrence of disease within two years of definitive surgery. Urinary PKM2 levels were measured and evaluated for their ability to predict response to treatment and two-year disease-free survival.
Results: Immunohistochemistry revealed high levels of PKM2 within muscle invasive tumors compared to adjacent tissue. Patients with BCa had 150-fold increase in levels of urinary PKM2 compared to controls. However, there were no differences in urine PKM2 levels in patients with complete pathological response compared to those with no response. Urine PKM2 showed limited predictive value for disease recurrence (area under receiver operating characteristic curve = 0.65).
Conclusion: Urine levels of PKM2 are significantly elevated in patients with muscle invasive BCa and may be useful for tumor detection. Urinary PKM2 is less effective at monitoring response to treatment and may instead represent a marker of urothelial susceptibility to tumor formation.
Citation Format: David Matye, Juliann Leak, Erika Abbott, Benjamin Woolbright, John Taylor. Urinary PKM2 in muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6417.
Abstract 6461: Prevalence and implications of potentially pathogenic germline variants among adult patients in the Philippines with solid malignancies who underwent tumor genomic profiling: A multi-institutional, cross-sectional study
Authors: Franco Paula Isabel Gimena , Que Frances Victoria , Andal Jose Jasper , Ang Daphne 
Published: March 2024

Abstract
Background: In high income countries, 2-10% of tumor genomic profiling reports reveal incidental pathogenic germline variants. A third of these patients would not qualify for genetic testing based on current guidelines. In South East Asia, despite increased use of outsourced genomic profiling platforms, there are no published studies exploring the prevalence of these potentially pathogenic germline variants (PPGV). Our study determined the prevalence of PPGVs among adult patients with solid malignancies who underwent liquid or tissue-based tumor genomic profiling in the Philippines.
Methods: Annotated reports of patients with solid cancers who underwent tumor genomic profiling using FoundationOne or FoundationOne Hemebetween January 2021 to July 2023 were reviewed (Ethical Board ID: SL-23143). PPGVs were identified according to recommendations from American Board of Medical Genetics and Genomics and expert review. PPGV criteria include having a variant allele frequency of &gt;30% and were categorized as: 1) high penetrance gene (HP), founder variant (FV), or variant associated with clinical presentation (VA). Cross-checking the pathogenicity through ClinVar database was also done.
Results: Out of 446 patients, 13 PPGV variants were found in 50 (11.2%) patients at a median age of 60.5 years. Of these, 28 (54%) had high penetrance (BRCA1, BRCA2, MSH2, MSH6, MLH1, RAD51C, RAD51D), 24 (46%) patients had VA (APC, SMAD4, CDH1, CDKN2A,PTEN) and two patients with lung cancer had a founder variant (EGFR p.Thr790Met). PPGVs were primarily found in colorectal (42% of 50 patients with PPGVs), breast (16%), ovarian (6%) and lung (6%) cancer patients (p&lt;0.001). HP genes were mostly found in females (71.4%, p = 0.03), driven by BRCA1/2 variants (15 females and 2 males).
Conclusions: The presence of PPGVs warrants formal genetic counselling and germline testing. Given the similar prevalence of PPGVs in this study compared with data from other countries, and the diagnostic and therapeutic implications of detecting incidental PPGVs, we underscore the need for cancer genetics to be incorporated into standard oncologic care in the Philippines.
Citation Format: Paula Isabel Gimena Franco, Frances Victoria Que, Jose Jasper Andal, Daphne Ang. Prevalence and implications of potentially pathogenic germline variants among adult patients in the Philippines with solid malignancies who underwent tumor genomic profiling: A multi-institutional, cross-sectional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6461.
Abstract 6473: Evaluation of bladder cancer patients' utilization of urologic telehealth services
Authors: Goldenthal Steven , Posid Tasha , Heh Victor , Denis-Diaz Dairon , Asif Hafsa , Arnold Chase , Gold Henry , Kim Tae-Hee , Ndumele Amara , Amin Sabrina , Lierz Matthew , Xu Vivian , Cronin Tyler , Khuhro Aliza , Lee Cheryl 
Published: March 2024

Abstract
Introduction: Infection control practices and public policy in response to the COVID-19 pandemic shifted healthcare practices towards a telemedicine format. Even two years after peak onset of the pandemic, many clinics, including our own institution, maintain a working telehealth option for patient visits. Our objective was to evaluate patient utilization of telehealth visits versus in-person visits at our institution and whether this was impacted by clinical stage, rural/urban status, distance from a large urban academic center, payor status, or comorbidities.
Methods: Medical Record Numbers for all patients with bladder cancer were pulled via the Qlik platform from the period 7/1/2019-2/28/2022. Chart review was conducted to pull clinical data on patients including telehealth versus in person visits, demographic data, clinical stage, comorbidities (diabetes, smoking status, BMI), rural/urban status by zip code (&gt;50,000, &lt;50,000 individuals) and income levels by zip code (25K-49.9K, 50K-99.9K, &lt;100K), payor status (Medicare, Managed care, Medicaid, other government, ODRC, or self-pay), patient distance, and gas savings/carbon footprint.
Results: 430 patients completed in person visits while 268 completed telehealth visits. There was no statistically significant difference for in person visits vs. telehealth visits regarding patients’ race (p=0.541), ethnicity (p=0.394) age (p=0.862), urban/rural status (p=0.507), payor status (p=0.127), mean zip code income (p=0.175), and comorbidities (p=0.626 for diabetes, p = 0.706 for smoking, p = 0.459 for BMI), and clinical stage (p=0.07). There was a statistically significant difference in mean distance (14.85 miles versus 26.86 miles, p&lt;0.01).
Conclusion: Patients’ with bladder cancer receive care from their urologist via in person visits versus telehealth at similar rates irrespective of their urban/rural status, demographics, payor status, relevant comorbidities, or relative income. Patients are more likely to engage in care with their urologist via telehealth if they live farther from a large urban academic center, which produces an economical and environmental impact via gas/time savings and reduced carbon footprint.
Citation Format: Steven Goldenthal, Tasha Posid, Victor Heh, Dairon Denis-Diaz, Hafsa Asif, Chase Arnold, Henry Gold, Tae-Hee Kim, Amara Ndumele, Sabrina Amin, Matthew Lierz, Vivian Xu, Tyler Cronin, Aliza Khuhro, Cheryl Lee. Evaluation of bladder cancer patients' utilization of urologic telehealth services [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6473.