bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B050: Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities
Authors: Mueller Christopher R , Parr Keira , Mates Mihaela , Robinson Andrew , Feilotter Harriet , Frosst Keira 
Published: November 2024

Abstract
We have developed a version of our "methylation DETection of Circulating Tumour" DNA (mDETECT) assay that is able to sensitively and quantitatively monitor Non-Small Cell Lung Cancer (NSCLC). We used this assay to frequently assess the tumour burden of a small cohort (17 individuals) of patients undergoing first line monotherapy with pembrolizumab for metastatic disease. Patients were tested weekly or biweekly in the period immediately after initiation of treatment with radiological assessment being done at approximately 3 months. Radiologically non-responding patients showed constant or increased mDETECT levels over the 3 month time frame. Responding patients showed 2 different patterns, with some showing dramatically increasing mDETECT levels for a short period of time followed by a rapid decrease. Other responders showed an immediate decrease within the first few week of treatment. In both responder groups these decreases were associated with a longer term response. Continued monitoring did reveal eventual progression in some of these patients with increasing mDETECT levels being seen 4 to 6 months before radiological changes. In some non-responding patients complex responses were seen, with mDETECT levels varying significantly over time. In one non-responding patient the addition of carboplatin to their treatment regime did produce a temporary improvement in their mDETECT levels. Frequent assessment of tumour burden by a liquid biopsy such as mDETECT offers the opportunity to rapidly determine a patient's response to therapy and potentially modify treatments to improve responses.
Citation Format: Christopher R Mueller, Keira Parr, Mihaela Mates, Andrew Robinson, Harriet Feilotter, Keira Frosst. Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities [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 B050.
Abstract B052: Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade
Authors: Wright Samuel J. , Zamora Izabella , Parikh Milan , Yeramosu Deepika , Bi Lynn , Kang Sarah , Rucevic Marijana , Sade-Feldman Moshe , Liu Baolin , Nguyen Ngan , Guess Jamey , Schneider Alexis , Lieb David , Woods Elliot , Michaud William , Lawless Aleigha R. , Sharova Tatyana , Kasumova Gyulnara , Kim Michelle S. , Park Ryan J. , Jenkins Russell W. , Klempner Samuel J. , Sullivan Ryan J. , Flaherty Keith T. , Hacohen Nir , Boland Genevieve M. , Mehta Arnav 
Published: November 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR018) of the Conference Program/Proceedings.
Citation Format: Samuel J. Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Lynn Bi, Sarah Kang, Marijana Rucevic, Moshe Sade-Feldman, Baolin Liu, Ngan Nguyen, Jamey Guess, Alexis Schneider, David Lieb, Elliot Woods, William Michaud, Aleigha R. Lawless, Tatyana Sharova, Gyulnara Kasumova, Michelle S. Kim, Ryan J. Park, Russell W. Jenkins, Samuel J. Klempner, Ryan J. Sullivan, Keith T. Flaherty, Nir Hacohen, Genevieve M. Boland, Arnav Mehta. Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade [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 B052.
Abstract B074: Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care
Authors: Woldesonbet Zelalem Desalegn , Yohannes Meron , Porsch Martin , Stückrath Kathrin , Anberber Endale , Santos Pablo , Bauer Marcus , Addissie Adamu , Bekuretsion Yonas , Assefa Mathewos , Worku Yasin , Taylor Lesley , Abebe Tamrat , Kantelhardt Eva J , Vetter Martina 
Published: November 2024

Abstract
Objective: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. Patients and methods: Formalin-fixed paraffin- embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. Results: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. Conclusion: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary-level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context.
Citation Format: Zelalem Desalegn Woldesonbet, Meron Yohannes, Martin Porsch, Kathrin Stückrath, Endale Anberber, Pablo Santos, Marcus Bauer, Adamu Addissie, Yonas Bekuretsion, Mathewos Assefa, Yasin Worku, Lesley Taylor, Tamrat Abebe, Eva J Kantelhardt, Martina Vetter. Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care [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 B074.
Abstract IA007: Modulating cfDNA biology to enhance liquid biopsies
Authors: Adalsteinsson Viktor 
Published: November 2024

Abstract
Liquid biopsies could transform cancer care but require higher sensitivity to detect early-stage tumors and minimal residual disease (MRD) and to enable tumor molecular profiling and therapy response monitoring for most patients. In this talk, I will focus on the significant biological bottlenecks upstream of cell-free DNA (cfDNA) testing. I will posit that in many circumstances, insufficient circulating tumor DNA (ctDNA) drawn in a blood tube cannot be overcome by assay technology alone, and that in vivo modulation of cfDNA biology may also be required to enhance liquid biopsies. Inspired by widespread use of diagnostic drugs in other areas of medicine, we sought to create the first “priming agents” for liquid biopsies that could be administered before a blood draw to recover more ctDNA. I will describe two such approaches—a monoclonal antibody against double-stranded DNA and a liposome nanoparticle—that briefly attenuate cfDNA clearance by shielding it from nuclease digestion and cellular uptake. These enabled &gt;10x more ctDNA to be collected when administered within 1-2 hours of a blood draw in mice. This improved the analytical limit of detection for ctDNA testing by &gt;10-fold, provided more complete representation of the tumor genome in each blood sample, and increased the sensitivity for detection of small tumors from &lt;10% to &gt;75% in mice. Envisioning a future where liquid biopsies are optionally enhanced with priming, I will also explore a unique potential pairing with our tumor-informed, whole-genome, mutation enrichment sequencing MRD test called MAESTRO, and how it stands to enable routine ctDNA detection below 1 part per million.
Citation Format: Viktor Adalsteinsson. Modulating cfDNA biology to enhance liquid biopsies [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 IA007.
Abstract IA018: Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection
Authors: Bratman Scott V 
Published: November 2024

Abstract
Head and neck cancer (HNC) is a molecularly heterogenous disease with a variable clinical course. Current treatment decisions rely primarily on pre-treatment prognostic factors without consideration of treatment response. This presentation will introduce liquid biopsy biomarkers that can be repeated in HNC patients for the purpose of dynamic risk stratification, treatment adaptation, and post-treatment surveillance. Novel approaches to measuring circulating tumor DNA (ctDNA) will be described, with particular attention to viral-associated and non-viral- associated subtypes of HNC. Detection of molecular residual disease (MRD) using ctDNA will be discussed. As HNC is often treated by non-surgical means, there is a pressing need for tissue- agnostic methods for ctDNA-based MRD detection. Analysis of tumor-specific genetic and epigenetic aberrations within ctDNA each present distinct opportunities and challenges for tissue-agnostic characterization of ctDNA. Viral ctDNA has emerged as a convenient target for MRD detection in viral-associated HNC, while ctDNA methylome profiling offers a versatile approach for tissue-agnostic MRD detection across HNC subtypes. Future applications of these methods may improve individualized management of HNC patients without requiring access to precious tumor tissue samples.
Citation Format: Scott V Bratman. Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection [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 IA018.
Abstract 4126895: Bridging the Gap in San Joaquin Valley LGBTQ+ Cardiovascular Disease and Mental Health Disparities
Authors: Siddiqui Maha 
Published: November 2024

Introduction:
LGBTQ+ adults experience discrimination and violence that lead to stressors in daily life. Homophobia affects the mental health of the growing San Joaquin Valley (SJV) LGBTQ+ community leading to psychological distress and mental health concerns which can further lead to High Blood Pressure (HBP) and cardiovascular disease (CVD). SJV has a growing rate of LGBTQ+ migrants from the Bay Area who may be at risk for psychological distress and CVD. With a diverse community of low income and minority groups, the lack of physicians do not represent the workforce of SJV.

Objectives:
Trainees conducted Kessler psychological distress tests, HBP and CVD screenings across college campuses and community events to reduce the risk of CVD and spread awareness about mental health, CVD and its implications in the LGBTQ+ population due to environmental racism in the most underserved region for health care, SJV.

Methods:
I trained and provided mentorship to medically ambitious diverse low-income high school to instill a passion in them to come back after their medical education to practice medicine and promote LGBTQ+ health equity in SJV. Students conducted weekly Kessler psychological distress tests, HBP screenings and serve as a health technology coach. Each student monitored 2 hypertensive and psychological distressed patients. Kessler psychological distress tests and CVD screenings were conducted at college campuses to spread awareness about LGBTQ+ mental health and heart health and track psychological distress and HBP in the LGBTQ+ community.

Findings:
-About 88% (98 of 112) experienced some form of discrimination from a health care professional

-About 57% (64 of 112) of SJV LGBTQ+ population are at risk for CVD
-About 14% (16 of 112) of SJV LGBTQ+ population are Stage 1 hypertensive
-About 76% (83 of 112) of SJV LGBTQ+ population are at risk for hypertension and are psychologically distressed

Direct Outcomes:
-Youth learned the value of empathy and service to disadvantaged LGBTQ+ communities through the program and volunteering

-LGBTQ+ empowerment and students are determined to pursue medicine and address community concerns
-Awareness, education among LGBTQ+ community for better heart and mental health
-Better understanding in how to manage and seek referral for mental health and health systems concerns
-Students learned about SJV health disparities and applied precision medicine to their own health inequity projects in SJV
-Improved LGBTQ+ patient provider trust
Abstract 4134483: How succesfully can we presribe the 'four pillars' of medications for patients with heart failure with reduced LV systolic function?
Authors: Bain Robert , Walters Mark , Wickham Keeley , Jones Rachel 
Published: November 2024

Introduction:
European, American and UK guidelines all endorse the prescription of the 'four pillars' of treatment (ACE/ARBs, b-blockers, MRAs and SGLT2 inhibitors) for heart failure with reduced LV systolic function (HFrEF). Many doctors believe that it is difficult to initiate and maintain patients on all these medications. We have studied 162 consecutive patients referred to our service as outpatients from primary care, subsequently diagnosed as having HFrEF, and our ability to establish them on these medications.

Methods:
Patients referred with potential heart failure (signs, symptoms and raised BNP) were identified as having HFrEF by echocardiography using British Society of Echocardiography (BSE) criteria. Patients attended regular outpatient appointments with a consultant cardiologist and specialist heart failure nurse and were prescribed and uptitrated all appropriate medications with any contraindications and intolerances noted.

Results:
Table 1 shows the number of patients sucessfully established on maximally tolerated doses of each class of medication. Reasons for not prescibing or discontinuing were: CKD 6, severe aortic stenosis 5, asthma 3, symptomatic bradycardia 5, hypotension 3, type1 diabetes 2, syncope 1, Raynauds 1, patient choice 8 and 6 patients died before all appropriate medications could be initiated. In 10 cases no clinical reason could be identified.

It can be seen that a high proportion of patients were successfully established on each individual class of medication and more than two thirds of patients were able to be maintained on all four classes of therapy.
Table 2 shows the breakdown of prescribing success according to the severity of LV dysfunction. It can be seen that prescribing success appears to be higher in those with the more severe LV dysfunction.

Conclusions:

1. The majority of patients can be established and maintained on appropriate polypharmacy for the treatment of LV systolic dysfunction.
2. The severity of LV systolic dysfunction is not a negative predictor of success in prescribing.
Abstract 4134778: Myocardial Recovery and Survival after Weaning of Left Ventricular Assist Device Therapy in Patients with Toxic and non-Toxic Cardiomyopathy, A Canadian Experience
Authors: Lalancette Jean-Simon , Belzile David , Cinq-Mars Alexandre , Dubois-Senechal Sacha-Michelle , Lemay Sylvain , Rimac Goran , Turgeon Pierre Yves , Morin Joelle , Bourgault Christine , Leblanc Marie-Helene , Dupuis Celine , Charbonneau Eric , Laflamme Maxime , bernier mathieu , Beaulieu-Shearer Alexander , Senechal Mario 
Published: November 2024

Left ventricular assist devices (LVAD) are increasingly used in refractory heart failure, mainly as a bridge to transplant or as destination therapy. LVAD unloading of the left ventricle (LV) can also promote myocardial recovery leading to improvement of the LV systolic function, allowing LVAD explantation. However, parameters associated with LVAD weaning and long-term outcomes are not well documented. The aim of this study was to assess the clinical and echocardiographic characteristics of weaned patients and to evaluate their event-free survival post-explantation.
We conducted a single-center retrospective study recruiting patients who underwent a second or third generation LVAD implantation at a Canadian cardiology center between November 2009 and October 2021.
A total of 98 patients underwent LVAD implantation during this period. All patients were on guideline-directed medical therapy (GDMT). Fourteen patients (14%) had significant LV recovery and were explanted/decommissioned after a median support time of 309 days (range 55-595 days). Toxic cardiomyopathy, defined as abuse of amphetamines (n=2), energy drinks (n=2) or multiple substances (n=6), was the most likely diagnosis in 10 of the weaned patients (71%). The LVEF was significantly higher and the left ventricular end-diastolic diameter (LVEDD) was significantly lower in weaned patients compared to unweaned patients after 3 months of support. Myocardial recovery manifested as pump thrombosis in 4 of the weaned patients (29%). Prior to explantation, 12 patients had a decrease in GDMT doses to minimize post explantation vasoplegia. After explantation, median follow-up time was 40 months (range 8-109 months) and the majority of patients were anticoagulated for 3 months. At last follow up, the LVEF was 44±6% and no patient had a LVEF below 35%. All patients were NYHA I or II and no death, heart transplant, or mechanical support initiation occurred.
LVAD therapy can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially young patients with toxic and non-ischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months following implantation is associated with successful weaning. Pump thrombosis seems to be associated with LV reverse remodeling and weaning of mechanical support in certain patients. Weaned patients maintain satisfactory LVEF recovery after explantation and have good long-term event-free survival.
Abstract 4136700: Sodium-Potassium Pump: Newly O-GlcNAc Protein Offering Potential Benefits in Hemorrhagic Shock situation
Authors: Vergnaud Amandine , Dupas Thomas , Aillerie Virginie , Persello Antoine , Erraud Angelique , Girardeau Aurore , Oliveira Mendes Barbara , Montnach Jerome , De Waard Michel , Rozec Betrand , Lauzier Benjamin 
Published: November 2024

Hemorrhagic shock(HS) results from significant blood loss, leading to insufficient oxygen delivery, which causes metabolic changes and multi-organ dysfunction.The HS-related acute kidney injury developed by the patient are mainly due to alteration in Na/K ATPase.In previous O-GlcNAcylomic studies, we identified the Na/K ATPase as potentially O-GlcNAcylated.O-GlcNAcylation, a post-translational modification, plays a role in various cellular processes, such as cell survival and stress response.O-GlcNAcylation may have beneficial effect in shock situations.
The objective of this study is to ascertain whether Na/K ATPase is O-GlcNAcylated and to elucidate its potential role during HS.
Hemorrhagic shock was induced by an exsanguination of rats.They were then randomly treated or not with an O-GlcNAcase inhibitor, the NButGT(10mg/kg), to increase O-GlcNAc level.Blood pressure and heart rate were monitored throughout the experiment.Blood samples were collected for complete blood analysis, including biochemistry and gas measurements. kidneys were immediately frozen for histological and biochemical studies.To study the O-GlcNAcylation of Na/K ATPase an immunoprecipitation and Wheat Germ Agglutinin(WGA) based lectin affinity gel electrophoresis were used. HEK cells were treated with or without NButGT(100µM,6 hours) and/or ouabain(Na/K ATPase inhibitor) and a colorimetric kit was assessed to study O-GlcNAcylation impact on Na/K ATPase activity.
O-GlcNAc levels increased by 2 folds in heart and kidney due to the NButGT treatment(p<0.05).Mean arterial pressure(MAP,p<0.01) and bicarbonate(p<0.01) are restored in treated group as kalemia(Sham:4.2 ± 0.1;HS:4.7±0.1;NButGT:4.3 ±0.1;mmol/L;p<0.05) and natremia(Sham:141.5±0.4;HS:139.8±0.5;NButGT:141.9 ±0.4; mmol/L;p<0.01).The study of the O-GlcNAcylation of the Na/K ATPase validated its O-GlcNAcylation.Histological analysis of the kidney showed that HS decreased Na/K ATPase expression, but treatment restored it(Sham:15.1±1.1;HS:10.3±0.6;NButGT:13.78±1.1;%area;p<0.05). An acute increase in O-GlcNAc levels through NButGT enhances Na/K ATPase activity.
Increased O-GlcNAcylation during hemorrhagic shock restored MAP and reduced indicators of metabolic acidosis.Treatment with NButGT restored natremia and kalemia.This effect is linked to an increase in the expression and activity of Na/K ATPase.Our study is the first to confirm that Na/K ATPase is regulated by O-GlcNAcylation, particularly in terms of its localization and stability.
Abstract 4137342: Prolonged Bazett’s corrected QT interval is associated with cardiovascular events and sudden death in Japanese patients with cardiovascular risk
Authors: Hirata Yuki , Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi 
Published: November 2024

Background:
QT durations are sex-dependent, with women having longer QT durations than men. In addition to congenital long-QT syndrome, prominent QTc prolongation is a risk for sudden death. There are several correction formulas for the QTc interval, but the association between the QTc interval and cardiovascular events by type of correction in patients at cardiovascular risk remains unclear.

Hypothesis:
Prolonged QTc duration is associated with cardiovascular events and sudden death in patients at high cardiovascular risk.

Methods:
We enrolled 4,654 subjects from the Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry), who had one or more cardiovascular risk factors. We used two different definitions of QT prolongation: Bazett’s corrected QT interval (QTcB) and Fridericia’s corrected QT interval (QTcF). QTc was divided into quartiles by gender, and quartile associations with the primary endpoint (composite cardiovascular events: cardiovascular death, nonfatal myocardial infarction/stroke) and secondary endpoint (sudden death) were compared.

Results:
QTc duration in females (QTcB: median 428 [IQR 414–444] ms, QTcF 422 [IQR 409–436] ms) was slightly longer than that in males (QTcB: median 419 [IQR 405–435] ms and QTcF 415 [IQR 402–430], both p<0.001). The mean follow-up period was 53 ± 17 months, during which 159 primary endpoints and 14 secondary endpoints occurred.

The longest QTcB group (Q4: ≥ 435 ms in men, ≥ 444 ms in women) had significantly more cardiovascular events than the other quartiles (vs. Q1: p=0.016, vs. Q2: p=0.037, and vs. Q3 p=0.141), and sudden death was more common than in Q2 and Q3 (vs. Q2 0.003, vs. Q3: p=0.032).
On the other hand, the longest QTcF group (Q4) (≥430 ms for men, 436 ms for women) had significantly more cardiovascular events than the Q1 and Q2 groups but not the Q3 group (vs. Q1: p=0.016, vs. Q2: p=0.037, and vs. Q3: p=0.141); sudden death was not significantly different among quartiles (all P>0.05).

Conclusions:
In Japanese patients at cardiovascular risk, prolonged QTcB was associated with cardiovascular events as well as sudden death.