bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B054: Using FRAGILE score to capture context-dependent cfDNA fragmentation patterns for inference on their tissues-of-origin
Authors: De Subhajyoti 
Published: November 2024

Abstract
Cell-free nucleic acids circulating in blood and other body fluids are usually highly fragmented and derived from multiple different tissue types, which makes it challenging to obtain information about their cellular and contextual origin. Analyzing low coverage cell-free DNA whole genome sequencing data from 243 healthy individuals, we showed that cfDNA fragmentation and degradation patterns vary depending on their underlying genomic and epigenomic contexts. We developed a composite index called FRAGILE Score (FRagment of Atypical GC and Irregular Length Enrichment Score) to capture the structure, sequence, and fragmentation-related properties of cell-free, and showed that the score carried information about the epigenomic contexts of the cfDNA fragments. A deconvolution approach based on the score predicts the cell type contribution in serum cfDNA from healthy individuals and cancer patients. We collected blood and urine of a cohort of 30 bladder urothelial carcinoma patients, and found that cfDNA derived from blood and urine had very different fragmentation characteristics. An analysis of cfDNA from paired urine and blood samples from this showcased utility of the score in predicting clinical and pathological characteristics non-invasively for clinical management of the patients.
Citation Format: Subhajyoti De. Using FRAGILE score to capture context-dependent cfDNA fragmentation patterns for inference on their tissues-of-origin [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B054.
Abstract B062: Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations
Authors: Koduru Srinivas V , Kidd Mark , Pieters Ané , Nagel S E , Millar Robert P , Halim Abdel B 
Published: November 2024

Abstract
Introduction: Prostate cancer is the most frequently diagnosed cancer across 112 countries. Among American men, an estimated 299, 010 new cases and 35,250 deaths are projected for 2024. In this study, the transcriptomic profile of prostate cancer patients from geographically and ethnically diverse cohorts (USA-Caucasian, RSA-Black) were compared to identify gene expression patterns associated with prostate cancer. Methods: Whole blood samples were collected from PCa and controls. Controls had the same age-range as PCa with no clinical indication of prostatic disease and serum PSA levels below 1.5 ng/ml. RNA was isolated, sequencing was carried out on Novaseq 6000, and data analyzed using PartekFlow to identify differential gene expression patterns (RSA-PCa: 6, RSA-Control: 6, USA-PCa: 7, USA-Control: 11). qRT-PCR was undertaken on a cohort of 27 biomarkers (PROSTest) related to PCa in whole blood. Results: Differential expression analysis identified distinct patterns in USA and RSA groups. In the USA PCa cohort, 2,193 genes were differentially expressed compared to the controls with fold change (FC) &gt;1, p-value (p) &lt;0.05, while in the RSA PCa cohort, 1,627 genes were differentially expressed compared to the controls. Pathway analyses identified enrichment for immune responsive genes in the RSA cohorts. We identified that 26 of 27 Wren’s PROSTest genes detectable in both groups. RNAseq and normalized PCR gene expression were well- correlated (r=0.44, p=0.0012, n=30 pairs). Conclusion: Based on this RNAseq study, there may be geographic differences related to ethnicity in overall blood RNA gene expression. We specifically identified alterations in immune function gene expression between the USA and RSA. Importantly, PROSTest genes were detected in both populations and exhibited a significant correlation. Development of gene signatures for biomarker discovery should, however, consider specific ethnicities and geographical regions.
Citation Format: Srinivas V Koduru, Mark Kidd, Ané Pieters, S E Nagel, Robert P Millar, Abdel B Halim. Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B062.
Abstract B069: Spatial and single-cell proteomic landscaping of the hypoxic microenvironment in glioblastoma
Authors: Gandhi Shreya , Mansouri Sheila , Singh Olivia , Zaidi Mark , Wu Ronald , Gao Andrew , Wouters Bradley , Zadeh Gelareh 
Published: November 2024

Abstract
Glioblastoma (GBM) is a fatal adult solid tumour with median overall survival of 18-20 months post-diagnosis; contributing factors to therapeutic inefficacy include acquisition of genomic alterations post-therapy, immune evasion, deregulated hypervascularization, and tumor microenvironmental factors such as hypoxia. Combined with extensive inter- and intra-tumoral heterogeneity at bulk and single-cell level, hypoxia contributes to a gradient of molecular alterations that are specific to different cell populations that make up tumour bulk and reside in specific niches. Hitherto, high-dimensional histopathologic analyses of hypoxic regions within GBM tissue have not been performed. We took a combined spatial and single-cell proteomic profiling approach to investigate the histopathologic features of hypoxia by leveraging a unique clinical study wherein the exogenous hypoxia marker, pimonidazole (PIMO), was administered to GBM-patients preoperatively. Tissue specimens were subjected to imaging mass cytometry, high-resolution imaging, and serial immunohistochemistry using a panel of markers associated with cellular hallmarks of hypoxia, metabolism, proliferation, stemness, angiogenesis, and immune cell types. Our findings showed that PIMO staining is associated with histopathologic features of hypoxia and correlates with specific metabolic, immune, and stemness markers in GBM; specific lymphocyte populations were depleted from hypoxic regions alongside alterations in macrophagic and microglial landscape in a niche-specific manner; hypoxia reduced the proportion of proliferating glioma initiating cells and altered the proliferative, transcriptional, and translational capacity of different cell populations; microvessel density was reduced in hypoxic microenvironment. Cytometry by time-of-flight further validated the altered proportions of specific immune cell types enriched in hypoxic populations of GBM microenvironment. Our study is the first to report use of PIMO to interrogate spatial, single-cell, and phenotypic architecture associated with tissue hypoxia and altered expression of biomarkers associated with hypoxia/glycolysis, immune infiltration, proliferation, and stemness. Identification of targetable biomarkers and mediators of hypoxia-driven habitats in GBM may provide direction for future immunotherapeutic research.
Citation Format: Shreya Gandhi, Sheila Mansouri, Olivia Singh, Mark Zaidi, Ronald Wu, Andrew Gao, Bradley Wouters, Gelareh Zadeh. Spatial and single-cell proteomic landscaping of the hypoxic microenvironment in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B069.
Abstract B072: Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach
Authors: Osei Kingsley A , Owusu Justina S 
Published: November 2024

Abstract
In Ghana, breast cancer leads in female cases (31.8%), demanding advanced treatments. Rising caffeine-filled energy drinks raise concerns. Yet, caffeine's role in breast cancer lacks understanding, urging more research. Our study uses network pharmacology and molecular docking to unravel the intricate molecular targets of caffeine in breast cancer, offering new therapies for this widespread disease We identified breast cancer-related targets from GEO datasets and TCGA databases, while caffeine targets were obtained from the SwissTarget Prediction database and literature. Common targets of both caffeine and breast cancer were considered using Venny software. PPI networks were generated using STRING and Cytoscape, identifying hub genes. Target proteins were annotated using the GO database, and pathway enrichment analysis was performed using KEGG. To investigate the binding affinity target proteins were retrieved from the Protein DataBank and docking studies were conducted using AutoDock Vina to explore the binding interactions between caffeine and potential target proteins identified. We identified 108 targets, and 6 common targets, including Cyclin-Dependent Kinase 1, Cyclin B1, Epidermal Growth Factor Receptor, Cyclin B2, Monoamine Oxidase A, and Carbonic Anhydrase 12 in relation to breast cancer. Gene Ontology (GO) and KEGG pathway enrichment analysis revealed their interactions in key pathways such as the P53 signaling pathway and Foxo signaling pathway, suggesting their critical roles in anti-breast cancer processes. Notably, caffeine exhibited the best overall binding affinity when interacting with CDK1, CCNB1, EGFR, and CCNB2 These findings provide valuable insights into the potential molecular targets and pathways associated with caffeine's anti-breast cancer effects, offering new strategies for therapeutic strategies.
Citation Format: Kingsley A Osei, Justina S Owusu. Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B072.
Abstract B075: Detection of early gastric carcinoma by micronuclei DNA from erythrocytes
Authors: Han Yuehua , Yao Xingyun , Sun Haobo , Fang Cheng , Li Peiwei , Liang Honghao , Jin Jie , Gao Xiaofei 
Published: November 2024

Abstract
Background: Advancements in non-invasive diagnostic technologies for gastric carcinoma (GC), including serum microRNA and cell-free DNA assays, have shown promise but still face challenges in achieving consistent early detection. Micronuclei (MN), extranuclear bodies harboring fragmented chromosomal segments, are indicative of genomic instability and have been employed in genotoxicity assessments and cancer diagnostics. We have developed a novel technique (WO2021/228246 A1) for the purification and characterization of micronuclei DNA (MN-DNA) extracted from erythrocytes in peripheral blood. Here, we evaluated the potential of micronuclei DNA (MN-DNA) from 2ml peripheral blood for early gastric carcinoma detection and explored its application for early cancer diagnosis. Methods: We assembled a clinical cohort consisting of 425 healthy donors (HDs) and 282 gastric cancer patients, from whom 1-2 mL peripheral blood samples were collected. Participants were randomly allocated into training, validation, and independent test cohorts in a 7:2:1 ratio, ensuring similar distributions of cancer stages and gender. MN-DNA was isolated from erythrocytes and subjected to comprehensive whole-genome sequencing. Predictive machine learning models were constructed utilizing distinct tumor-associated MN-DNA features identified through genome-wide analysis to distinguish between HDs and GC. Results: Comprehensive genome-wide analysis of MN-DNA demonstrated pronounced disparities in distribution patterns between HDs and GC patients. The predictive model built on MN-DNA features achieved an AUC of 97.69% (95%CI: 95.57- 99.81%), with an 96.47% specificity and 91.07% sensitivity in the independent test cohort. The model identified early GC (stage 0-I) and advanced GC (stage II-IV) with sensitivities of 95.24% or 78.57%, respectively. Conclusions: Our results demonstrate that MN-DNA from 1-2mL peripheral blood enable accurate detection of GC, especially in early GC. As a type of cytoplasmic DNA, MN-DNA can provide a valuable tool for early cancer detection, offering different underlying mechanisms compared to current methods. Research sponsor: Timing Biotech.
Citation Format: Yuehua Han, Xingyun Yao, Haobo Sun, Cheng Fang, Peiwei Li, Honghao Liang, Jie Jin, Xiaofei Gao. Detection of early gastric carcinoma by micronuclei DNA from erythrocytes [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B075.
Ponte Alta do Rio Aracahú
Authors: Paulino Peterson Mendes 
Published: November 2024

Esta é uma periferia nas fronteiras de uma das maiores cidades do Brasil. Marcada por um contraste entre a paisagem natural característica da Mata Atlântica, e as ocupações que surgiram da necessidade daqueles que clamavam pelo direito à moradia. Na região do Ponte Alta, formada pelos bairros Ponte Alta, Jardim Santa Paula, Comunidade Anita Garibaldi e Nova Ponte Alta, este ensaio revela os lugares que fazem parte da memória coletiva, e possuem o poder de contemplar em parte, sua história. Há refúgios naturais e frequentados pelos moradores, como mostrou-se em uma visita e um registro feito da Lagoa do Bonsucesso, bem como lugares de culto e religiosidade como a Capela São Geraldo no mês de maio com um florido ipê rosa. Nas fronteiras do Ponte Alta, um córrego conhecido como Guaraçau e antigamente denominado Aracahú, se destaca por ser a origem do nome desta comunidade, mas também por estar violado pela maldade humana, ocasionada pela poluição desenfreada. Nos limites do Jardim Santa Paula, um casarão em estilo neocolonial se destaca em meio a uma vegetação, casarão este remanescente do antigo Sítio Ponte Alta. No mais, no ponto mais alto do bairro, contempla-se uma paisagem incrível, simbólica e reveladora do nosso tempo: o marginal, a periferia, às margens e a produção capitalista do espaço urbano brasileiro.
As fotografias foram feitas na região do bairro Ponte Alta em Guarulhos, entre os meses de Janeiro a Outubro de 2022.
Abstract 4112775: Demographics and Cardiovascular Mortality Among Kaposi Sarcoma Patients in the United States: An Analysis of the SEER Database
Authors: Khan Rozi , Goyal Aman , Yasinzai Abdul Qahar Khan , Tracy Katharine , Sohail Amir , Ballur Shalini , Flesner Samuel , Mahmood Ahmed , Ballur Kalyani , Tareen Tamour , Sethi Pooja , Alexander Thomas , Ullah Asad 
Published: November 2024

Aims and Background:
Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus. Despite its significance, there is limited data regarding the causes and mortality factors associated with KS, particularly concerning cardiovascular mortality rates and specific influencing factors.

Methods:
The Surveillance, Epidemiology, and End Results (SEER) database was used to gather data from 2000 to 2020. The primary endpoint was overall survival, assessed via log-rank analysis and Kaplan-Meier plots. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using SAS v9.4, with significance set at p<0.05.

Results:
We identified 8,247 patients with KS. Most were male (90.6%) and aged 40-59 years old (38.5%).

Mortality data from KS showed that 56.3% of diagnosed patients were alive. Among those who died, 49.8% died of infectious causes, 11.4% died of cardiac causes, and the remaining died of other causes, such as leukemias and complications. Advanced age (>80 years) vs. 0-19 year age group (HR: 2.263; 95% CI: 1.068-4.795; p=0.033), non-Hispanic Black race vs. non-Hispanic White race (HR 1.492; 95% CI: 1.369-1.627; p=0.001), and visceral involvement vs. cutaneous KS (HR 1.709; 95% CI: 1.487-1.963; p=0.001) were factors associated with increased mortality. Females had a slightly lower long-term survival than males (p<0.001). Married individuals, higher incomes (≥$75,000), and urban areas of living had higher survival rates compared to widowed patients, lower-income patients (<$75,000), and those in rural locations, respectively (p<0.001, for all).
In the subgroup analysis, females (24.3%; n=112) had significantly higher cardiac-related deaths than males (9.5%; n=297) (p<0.0001). Cardiac-related deaths were highest in White patients (16.1%; n=279), followed by Hispanics (10.4%; n=79).

Conclusions:
Cardiac causes accounted for 11.4% of deaths. Various factors are associated with an increased mortality risk.
Abstract 4117310: Alcohol-Related Cardiomyopathy - Exploration of Recent Mortality Trends in the United States
Authors: Aun Muhammad , Mughal Mohsin 
Published: November 2024

Introduction:
Data is accumulating regarding the contemporary trends of mortality rates in patients with alcohol-related cardiomyopathy across the United States.

Hypothesis:
We hypothesized that with increased awareness about the adverse effects of alcohol on the cardiovascular system and the advancement of echocardiography in the early diagnosis of alcoholic cardiomyopathy, mortality rates may show a downward trend.
Methods:
This is a retrospective observational study that retrieved death certificates from the CDC WONDER (Center for Disease Control and Prevention’s Wide-ranging ONline Data for Epidemiological Research) database from 2001-2020. The mortality rate of alcohol-related cardiomyopathy using ICD code I42.6 (Alcoholic cardiomyopathy) was studied from 2001-2020. This study duration was further subdivided into five-year periods. We calculated the crude mortality rate and age-adjusted mortality rate per 100,000 for four U.S census regions (CR-1 Northeast, CR-2 Midwest, CR-3 South, CR-4 West).
Results:
The overall age-adjusted mortality rate remained at 0.1/100,000 deaths in four U.S census regions until 2015; however, in the last five years of the study period, AAMR(age-related mortality rate) increased from 0.1 to 0.2/100,000 deaths.
Conclusions:
The mortality trends associated with alcohol-related cardiomyopathy have not changed significantly over the past two decades. This can be explained by the larger number of people developing alcoholic cardiomyopathy due to the increase in global alcohol use in addition to the fact that more diagnosed patients are receiving earlier treatment with goal-directed medical therapy for cardiomyopathy. Limitations of this study include intrinsic weakness of the WONDER dataset (changes with ICD-9 to ICD-10 codes, and potentially miscoding) which needs further research.

Discussion:
This suggests that while mortality rates associated with alcohol-related cardiomyopathy remained relatively steady for most of the study period, there was a concerning uptick in the latter years. This could prompt further investigation into potential factors contributing to this increase, despite advancements in awareness and diagnostic techniques.
Abstract 4118342: Acoustic Analysis For The Detection Of Leaflet Thrombosis After Transcatheter Aortic Valve Replacement
Authors: Lupu Lior , Shetrit Aviel , Kadosh Adi , Aviram Galit , Topilsky Yan , Banai Shmuel , Havakuk Ofer 
Published: November 2024

Introduction:
Following trans-catheter aortic valve replacement (TAVR), patients may develop aortic valve leaflet thrombosis, a condition associated with an increased risk of embolic events. Currently, the diagnosis of post-TAVR leaflet thrombosis is based on echocardiography surveillance or cardiac tomography (CCT) scan, both require specialized team and equipment, and may also expose the patients to radiation and contrast.

Acoustic analysis is a non-invasive reproducible method, which incorporates the recording of cardiac sounds and analyzing them via machine learning algorithms.
Here, we investigated the diagnostic abilities of acoustic analysis in the detection of post-TAVR leaflet thrombosis.

Methods:
Using an electronic stethoscope, heart sounds were prospectively recorded at 2 time points: 24-hours and 6-months post-TAVR. CCT scan was performed 6-months following TAVR to detect leaflet thrombosis. Acoustic sounds were analyzed, using a Gaussian support vector machine (SVM) algorithm, to identify features associated with leaflet thrombosis.

Results:
Of 19 consecutive patients, 3 were found to have high-grade leaflet thrombosis based on CCT results. The SVM algorithm effectively classified heart sounds into "normal" and "thrombotic", with a sensitivity of 100% and specificity of 97.2%. Following anticoagulation therapy, all 3 patients showed no signs of leaflet thrombosis on follow-up CCT scans and were also classified as "normal" by the algorithm. Notably, at the time of leaflet thrombosis, Doppler echocardiographies showed normal pressure gradients across the affected valves.

Conclusions:
These initial results suggest that acoustic analysis, combined with machine learning algorithms, may identify post-TAVR leaflet thrombosis, providing a non-invasive, cost-effective, and radiation-free alternative to traditional diagnostic methods.
Abstract 4125999: Elderly patients with HF with reduced ejection fraction and renal failure: are SGLT2i a good option?
Authors: Balaguer German jorge , CORTES GARCIA MARCELINO , Rodriguez Lopez Carlos , Romero Otero Jose Maria , Esteban Chapel Jose Antonio , Nieto Roca Luis , Taibo Urquia Mikel , Pello Lazaro Ana Maria , Tunon Jose 
Published: November 2024

SGLT-2 receptor inhibitors (SGLT-2i) have been shown to reduce cardiovascular mortality and hospitalisations for heart failure (HF) in patients with HF with reduced ejection fraction (HFrEF) and to have a nephroprotective role in patients with chronic kidney disease (CKD). However, the available evidence in patients older than 75 years and with CKD is limited.
We conducted a retrospective, single-centre study including patients aged >75 years diagnosed with HFrEF (defined as ejection fraction <40%), CKD (eGFR <60mL/min) and with an indication for treatment with SGLT-2i for HF between November 2019 and November 2022. Clinical, analytical, electrocardiographic and echocardiographic variables were collected.
A total of 173 patients were included with a mean follow-up of 31.6 months (SD ±13.2). Mean age 84.7 years (SD ±4.9), 66.5% were male, 85.5% were hypertensive, 34.7% diabetic and 39.3% dyslipidaemic. Peripheral vascular disease was present in 11.6%. Mean glomerular filtration rate was 45.9 mL/min and only 2.3% were on haemodialysis. LVEF at inclusion was 29.5% (SD ±7.9), with 53.1% being of ischaemic aetiology and the most frequent functional class being NYHA II (53.2%). Thirty-seven percent had atrial fibrillation and 34.1% had complete left bundle branch block. At the end of follow-up 80.3% were on beta-blockers, 48.6% on ACE inhibitors, 37.6% on aldosterone antagonists, 23.7% on ARNI and only 11% on SGLT-2i.
Survival analysis was performed using Cox logistic regression (multivariate analysis), where SGLT-2i was shown to be the only protective factor for all-cause mortality (HR 0.3 [0.1-0.9]). Male sex (HR 2.2 [1.3-3.9]) and diabetes (HR 1.6 [1.0-2.6]) were associated with higher mortality. The attached figure (figure 1) shows the Kaplan-Meier survival curves for total mortality in those patients with and without SGLT-2i (p log-rank 0.05).
In our population, SGLT2i showed a significant reduction in total mortality in patients older than 75 years, with HFrEF and CKD. However, the treatment rate in this subgroup of patients is very low. Further implementation of SGLT2i treatment in this type of patient could be of significant clinical and prognostic benefit.