bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B061: Assessing saliva for cancer biomarker discovery: A liquid biopsy approach
Authors: Koduru Srinivas V , Kidd Mark , Halim Abdel B 
Published: November 2024

Abstract
Introduction: Liquid biopsy has been gaining traction as a replacement for invasive tumor biopsies in oncology. Several blood-based in vitro diagnostics have been approved by the FDA and other regulatory agencies, and efforts are being made to validate urine, saliva, and buccal swabs as alternative matrices. The primary aim of this study was to investigate the relative mRNA expression in paired blood and saliva samples from cancer patients and healthy individuals. Methods: We collected matched saliva and blood samples from 35 subjects, comprising 26 patients with prostate, breast, colon, lung, melanoma, and pancreatic cancers, and 9 healthy individuals. Samples were collected using Wren's proprietary stabilization buffer kit, and total RNA extracted by TRIzol-based Qiagen reagents. RNA sequencing (RNA-Seq) was performed on a Novaseq 6000 platform, and data was analyzed using high-performance computing (HPC) with PartekFlow software, employing the BWA aligner (hg38). We focused on comparing gene expression in cancers (as a group) compared to controls. Results: The total number of genes detected in saliva was 3,985, compared to 14,459 genes detected in blood samples. A substantial overlap was observed, with more than 92.8% of saliva-detected genes also found in blood. We also examined housekeeping gene detection in both matrices. In this set of 1,003 housekeeping genes, 30% (n=305) were expressed in both saliva and blood. When we narrowed the scope to only include the 1,154 cancer-related genes as listed by the OncoKB database, 88.3% were detected in saliva and/or blood, with 37.1% of these genes (n=429) were expressed in both saliva and blood. Lastly, we examined a set of 241 cancer-associated biomarkers utilized in RT-PCR-based diagnostic blood assays clinically validated by our laboratory. This subset analysis revealed that 23.2% of these biomarkers were expressed in both saliva and blood. Conclusion: Our data indicate that the majority of mRNA detected in saliva was also detected in blood, with differential expression observed in cancer patients compared to normal controls. Given the relatively high limit of detection (low sensitivity) using RNA-Seq technology compared to PCR and the relatively small number of subjects, the data may suggest that saliva could function as a surrogate biomarker matrix for blood.
Citation Format: Srinivas V Koduru, Mark Kidd, Abdel B Halim. Assessing saliva for cancer biomarker discovery: A liquid biopsy 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 B061.
Abstract IA005: Tumor cell-based liquid biopsy to characterize prostate cancer
Authors: Haber Daniel A , Maheswaran Shyamala , Guo Hongshan , Vuille Joanna , Huang Shih-Bo , Wittner Ben S , Sequist Lecia V , Lee Richard J , Brunker Patricia AR , Miyamoto David T , Mishra Avanish , Toner Mehmet 
Published: November 2024

Abstract
Circulating Tumor Cells (CTCs) hold the promise of comprehensive yet noninvasive molecular characterization of cancer cells during the course of tumor evolution and progression. To dissect the epigenetic profile of prostate CTCs, we undertook paired DNA methylation and RNA sequencing of single CTCs isolated from blood specimens of patients with prostate cancer. Across the genome, our study identified 40 core Partial Methylation Domains (PMDs) that arise early in tumorigenesis and are shared by all individual CTCs across multiple patients. Key among these is a single genomic locus harboring multiple interferon-inducible genes along with all the CD1 gene family members, implicated in innate immunity. Based on mouse models, we propose that early biallelic silencing of multiple genes residing within a single PMD may contribute to the escape from immune surveillance in prostate and potentially other cancers. Studies of CTC heterogeneity within individual patients are limited by the very small number of cells that can be isolated from standard 10ml blood volumes. To enable such analyses, we applied a new high throughput microfluidic platform, capable of processing an entire leukapheresis product, interrogating 2-3 L of blood volume equivalent. Applying this technology to patients with metastatic prostate cancer, we successfully enriched thousands of CTCs from individual cases, enabling the characterization of intra-patient heterogeneity at the level of cell morphology and marker expression, chromosome copy number variation and exome-wide genotyping, and transcriptionally-defined tumor cell subpopulations. Such high-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.
Citation Format: Daniel A Haber, Shyamala Maheswaran, Hongshan Guo, Joanna Vuille, Shih-Bo Huang, Ben S Wittner, Lecia V Sequist, Richard J Lee, Patricia AR Brunker, David T Miyamoto, Avanish Mishra, Mehmet Toner. Tumor cell-based liquid biopsy to characterize prostate cancer [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 IA005.
Abstract IA011: Heterogeneity of cancer-derived extracellular vesicles
Authors: Di Vizio Dolores 
Published: November 2024

Abstract
Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO). This study provides the first resource of label-free quantitative proteomics of LO and small EVs obtained from distinct cancer cell types (prostate, breast, and glioma). This dataset was integrated with a SWATH Proteomic assay on LO, rigorously isolated from the plasma of patients with metastatic prostate cancer (PC). Proteins enriched in LO, which were identified also at the RNA level, and found in plasma LO significantly correlated with PC progression. Single EV RNA-Seq of the PC cell-derived LO confirmed some of the main findings from the bulk RNA-Seq, providing first evidence that single cell technologies can be successfully applied to EVs. This multiomics resource of cancer EVs can be leveraged for developing a multi-analyte approach for liquid biopsy.
Citation Format: Dolores Di Vizio. Heterogeneity of cancer-derived extracellular vesicles [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 IA011.
Abstract IA017: ctDNA based detection of MRD in colon cancer: Towards clinical implementation
Authors: Tie Jeanne 
Published: November 2024

Abstract
Patient selection for adjuvant treatment remains a challenge with our current clinicopathologic criteria. While adjuvant chemotherapy has been shown to improve relapse risk and survival in stage III colon cancer and perhaps less so in stage II disease, the absolute benefit remains modest, risking the over-treatment of many patients and potential under-treatment of some. Additionally, beyond fluoropyrimidine and oxaliplatin, no new adjuvant therapy has been shown to improve survival over the past 2 decades, especially for MMR proficient tumors. The ability of ctDNA to detect minimal residual disease offers a paradigm shift to the conventional tissue- based risk assessment. Post-op ctDNA detection has been shown to be one of the strongest independent prognostic markers in curatively resected colorectal cancer. Alongside technological advancement, multiple randomized trials are investigating different applications of ctDNA MRD analysis in the clinic, from adjuvant treatment de-escalation in patients with ctDNA-negative result, treatment escalation in ctDNA-positive result to the role of ctDNA as a surveillance tool. Understanding the strengths and limitations of this test will help inform future trial design and optimize clinical implementation.
Citation Format: Jeanne Tie. ctDNA based detection of MRD in colon cancer: Towards clinical implementation [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 IA017.
Abstract IA025: A DNA methylation atlas of normal human cell types
Authors: Kaplan Tommy 
Published: November 2024

Abstract
DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.
Citation Format: Tommy Kaplan. A DNA methylation atlas of normal human cell types [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 IA025.
Uso de doxazosina off label para o alívio de pesadelos no contexto do Transtorno de Estresse Pós-Traumático: uma revisão sistemáticaresse Pós-Traumático: uma revisão sistemática
Authors: Ribas Gabriel de Oliveira , Cunha Sara Regina Corrêa , Calixto Amanda Vilela Nasser , Miranda Pedro Paulo Fagundes , Boze Ana Luísa , Koseki Fábio Yutani , Candido Carolina Pola 
Published: November 2024

A CID-10 define o Transtorno de Estresse Pós-Traumático (TEPT) como uma resposta prolongada e desproporcional aos eventos traumáticos, caracterizada por reexperimentação do evento traumático, esquiva persistente e hiperexcitabilidade. Neste contexto, estudos sobre pesadelos de eventos traumáticos têm ganhado notoriedade e, a doxazosina, um antagonista seletivo de receptor alfa-1 adrenérgico, surge como um fármaco potencial para o tratamento neste contexto. O objetivo desta revisão sistemática é elucidar os mecanismos de ação, eficácia, potenciais efeitos colaterais, preditores de resposta ao tratamento, considerações de segurança associados ao uso da doxazosina no contexto do TEPT, identificando lacunas na literatura. Materiais e Métodos: Essa revisão sistemática seguiu critérios das Diretrizes de Itens e Preferenciais para Revisões Sistemáticas e Meta-análises (PRISMA) e utilizou a estratégia PICO na formulação da pergunta norteadora. Utilizou-se para esta revisão as bases de dados Google Acadêmico, LILACS, PubMed e Science Direct. A análise foi conduzida com os descritores conforme a plataforma DECS/MESH (descritores em saúde): “Doxazosina”, “Transtorno de Estresse Pós-Traumático” e “Pesadelos”. Resultados: Dos artigos revisados, todos apresentaram resultados positivos para o uso da doxazosina no tratamento de pesadelos relacionados ao TEPT, embora muitos não tenham sido realizados em comparação com placebo. Relatos de casos demonstram uma melhora dos pesadelos, mesmo em casos graves com comorbidades. Alguns estudos observaram reduções significativas dos pesadelos após o tratamento. Apesar disto, o uso da doxazosina, com este intuito, ainda não se encontra como recomendação pela Academia Americana de Medicina do Sono, mesmo sendo uma alternativa à prazosina. Efeitos colaterais mais relatados foram sonolência e cefaleia, mas foram bem tolerados. Conclusão: Apesar de existirem controvérsias, conclui-se que o uso da doxazosina pode ser uma alternativa no tratamento dos pesadelos, no contexto do TEPT. Por fim, destaca-se a necessidade de mais pesquisas sobre esta temática.
Abstract 4126262: The impact of angiotensin receptor neprilysin inhibitors on the elderly population with heart failure and reduced ejection fraction: data from the real world
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

Heart failure (HF) remains a disease of increasing prevalence and morbidity. Validation of new lines of therapy in the elderly are required due to the progressive ageing of the world's population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyse the effect of Angiotensin Receptor–Neprilysin Inhibitors (ARNI) in this subgroup of patients. We conducted a single-centre, real-world observational study.
We consecutively enrolled all patients aged ≥75 years diagnosed with HFrEF (defined as an ejection fraction <40%) and theorical indication for treatment with ARNI from November 2019 to January 2021. The main outcomes analysed were all cause mortality and admission due to HF. In order to avoid potential confounding factors, we performed a propensity-score (PS) matched analysis. Patients matching was performed in a 1:1 ratio with the nearest neighbour method.
A total of 364 patients were recruited (total population). The mean age was 84.1 years of which 67% were male. 81% were hypertensive and 33.5% diabetic. The main cause of ventricular dysfunction was ischemic with 50.2%. At inclusion 55.8% were in NYHA functional class II and the mean LVEF was 29.8%. After PS matching, we selected 184 patients (study population), 92 with ARNI. As compared with non ARNI group, the ARNI patients showed higher use of mineralocorticoid receptor antagonists (MRA) (59.8% vs 43.5%, p< 0.05) and SGLT2 inhibitors (40.2% vs 6%, p<0.05). Other treatments were otherwise similar in both groups. There were not significant differences in relation with age, etiology or comorbidities between ARNI group and non-ARNI group. During a median follow-up of 39 months, total mortality was 31.5% (58 patients). After a Cox logistic regression analysis, ARNI therapy was shown to be an independent protective variable with respect to total mortality [HR 0.6 (0.4-1), p 0.05]. The figure shows the Kaplan-Meier survival curves for total mortality in patients with and without ARNI treatment.
In summary, treatment of HFrEF remains a significant challenge in managing HF patients, especially in the elderly. According to our data, treatment with ARNI in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show us that ARNI therapy could improve prognosis in the elderly with HFrEF in a real-world study.
Abstract 4131409: Systemic Review and Meta-analysis of Global Longitudinal Strain Changes after Angiotensin Receptor Nephrilysin Inhibitor Initiation in Patients with Heart Failure
Authors: Carter Kristen , Gupta Soumya , Correa Ashish , Mahmood Kiran , Fox Arieh 
Published: November 2024

Angiotensin Receptor Nephrilysin Inhibitors (ARNi) have been established as a beneficial medication in patients with heart failure (HF). This class of medications has been shown to decrease HF hospitalizations and has been included as one of the pillars in guideline directed medical therapy. Recently, left ventricular (LV) global longitudinal strain (GLS) measurements on echocardiograms have become more common and provide a more precise measurement of LV function than ejection fraction. GLS is now being used as a more intricate way of monitoring improvement in the function of the myocardium, especially in patients with heart failure. This meta-analysis was conducted to determine if treatment with ARNi in HF patients significantly improves myocardial functioning measured by LV GLS.
A meta-analysis of 9 studies including observational studies and randomized controlled trials found in a Pubmed search was performed and included patients with heart failure who were initiated on an ARNi for guideline directed medical therapy and had LV GLS measurements taken on an echocardiogram before and after ARNi initiation. The study included patients with heart failure with reduced ejection fraction. Studies were excluded if the patient population did not have a diagnosis of HF and if LV GLS measurements were not available before and after treatment with ARNi. This analysis was performed to determine if initiation of ARNi in patients with HF led to a significant improvement in LV GLS on echocardiography and therefore a significant improvement in myocardial function.
There were 9 studies included in the analysis and 879 patients with HF who were treated with ARNi or a control. The change in LV GLS at the conclusion of the study period was measured in both treatment and control groups and the mean difference between the two groups was -1.61 with a 95% confidence interval of (-2.23, -0.98) (p <0.00001). This indicates that the ARNi treatment groups had a significant improvement in GLS compared to the control groups.
ARNi initiation was found to significantly improve LV GLS and therefore myocardial function in patients with HF with reduced ejection fraction. LV GLS is a precise measurement of myocardial function. Using this form of measurement in echocardiograms can aid in determining the effect different treatments have directly on myocardial function.
Abstract 4136539: Management of Malignant SVC Syndrome and Acute SVC Thrombosis with Complex Endovascular Intervention
Authors: Fischer Karley , Reddy Ananya , Valencia Damian , Rehman Abdur 
Published: November 2024

Superior vena cava (SVC) syndrome occurs when there is SVC occlusion or obstruction. SVC obstruction can cause an increase in venous return pressure up to 40 mm Hg, producing edema of the face, neck and chest wall. Blood flow can be diverted to the right atrium through collateral venous networks in cases of gradual SVC compression. The most common cause of SVC syndrome is malignancy, as seen in 70% of cases. Traditionally, treatment is with radiation therapy but advances have now allowed for an endovascular approach. We present a case of malignant SVC syndrome with a complex percutaneous treatment approach that provided palliation with near immediate symptom improvement.
A 64 year-old-female with history of cerebrovascular accident on Eliquis, right upper lobe squamous cell carcinoma of the lung in remission, and a mediastinal nodule under surveillance presented with facial and bilateral upper extremity edema. CT revealed bilateral pulmonary embolism and a large SVC thrombus causing impaired venous return. Invasive angiogram confirmed a 95% thrombotic tubular stenosis for which she underwent aspiration thrombectomy with alpha VAC F-18, then angioplasty with an Armada (Abbott) 10 x 40 mm compliant balloon and stenting with the Express (Boston Scientific) 10 x 37 mm stent. There was 0% residual stenosis and immediate clinical improvement. Oncological workup confirmed the right mediastinal mass to be a recurrence of squamous cell carcinoma.
SVC syndrome occurred due to mediastinal mass compression and a near occlusive SVC thrombus. Aspiration thrombectomy was effective in treating the SVC thrombosis and was performed alongside pulmonary embolism thrombectomy. The Armada balloon is intended for lesion dilation in the peripheral arteries, but was safely used here for venous dilation. The Express stent is intended for palliation of malignant biliary neoplasms but has versatility and was utilized here for malignant neoplasm surrounding the SVC. Peripheral endovascular stenting is an advantageous treatment option for malignant SVC syndrome given the challenges due to recurrence from mass effect. This provides additional support to maintain vessel patency and is a safe palliation option for improvement in quality of life.
Abstract 4136754: Psychoactive medication use in pediatric heart transplant recipients: An assessment of prevalence, risk factors, and outcomes
Authors: Schauer Jenna , Aljohani Othman , Cantor Ryan , Fraser Anna , Haregu Firezer , Hope Kyle , Kirklin James , Thompson Consuela , Urschel Simon , Zaim Nadia , Zhao Hong , Brosbe Micah 
Published: November 2024

Background:
There is increasing recognition of the mental health burden experienced by pediatric heart transplant (HTx) recipients. Mental health concerns can impact physical health and increase risk of poor health outcomes. Using the Pediatric Heart Transplant Society (PHTS) database, we assessed the use of psychoactive medications as a proxy for mental health issues. We assessed the prevalence of psychoactive medication usage, pre- and post HTx factors, and post HTx outcomes associated with psychoactive medication usage.

Methods:
We queried the PHTS database for patients >5 years of age at time of follow-up who underwent HTx between January 2015 and June 2023. Patients with use of any psychoactive medication were identified. Sub-analyses were performed for use of antianxiety/antidepressant and attention-deficit/hyperactivity disorder (ADHD) medications. Multivariate logistic regression models were utilized to assess risk factors and impact on outcomes, including graft survival, coronary artery vasculopathy (CAV), and rejection at 1, 3, and 5 years post-HTx.

Results:
Among 1792 patients older than 5 at 1 year post HTx, 301 (16.8%) were prescribed at least one psychoactive medication; 246 (13.7%) were prescribed medication for antianxiety/antidepressant medications and 59 (3.3%) for ADHD. Utilization of psychoactive medication decreased at 3 years (14.8%, N= 240 of 1629) and 5 years post HTx (11.3%, N=230 of 2029).

Patients on psychoactive medications at 1 year post HTx tended to be older (OR=2.1, p<0.001), had higher priority listing status (OR=2.3, p<0.05), and longer bypass time (OR=1.6, p<0.05). Black patients were less likely to be prescribed psychoactive medication at 3-years post HTx than white patients (OR=0.57, p<0.05) or other races (OR=0.43, P <0.001).
There was no association of psychoactive medication usage on graft survival, CAV, or rejection at 1 year post HTx. At 3 years post HTx psychoactive medication usage was associated with significantly higher prevalence of CAV (p<0.05). At 5 years post HTx graft loss (p<0.005) and CAV (p<0.05) were significantly increased in patients on psychoactive medications.

Conclusions:
A significant proportion of pediatric HTx patients take psychoactive medications. This population may be at risk for worse long-term outcomes. There is a need to assess the mental health burden of pediatric HTx and to identify modifiable factors to improve assessment and treatment of mental health issues and its impact on outcomes.