bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with loss to follow‐up in patients with advanced age‐related macular degeneration: A telehealth recall initiative
Authors: Munzar Rachel , Roh Shiyoung , Ramsey David J. 
Published: March 2024

AbstractIntroductionPatients with advanced age‐related macular degeneration (AMD) frequently experience loss to follow‐up (LTFU), heightening the risk of vision loss from treatment delays. This study aimed to identify factors contributing to LTFU in patients with advanced AMD and assess the effectiveness of telephone‐based outreach in reconnecting them with eye care.MethodsA custom reporting tool identified patients with advanced AMD who had not returned for eye care between 31 October 2021 and 1 November 2022. Potentially LTFU patients were enrolled in a telephone outreach programme conducted by a telehealth extender to encourage their return for care. Linear regression analysis identified factors associated with being LTFU and likelihood of accepting care post‐outreach.ResultsOut of 1269 patients with advanced AMD, 105 (8.3%) did not return for recommended eye care. Patients LTFU were generally older (89.2 ± 8.9 years vs. 87.2 ± 8.5 years, p = 0.02) and lived farther from the clinic (25 ± 43 miles vs. 17 ± 30 miles, p = 0.009). They also had a higher rate of advanced dry AMD (26.7% vs. 18.5%, p = 0.04) and experienced worse vision in both their better‐seeing (0.683 logMAR vs. 0.566 logMAR, p = 0.03) and worse‐seeing (1.388 logMAR vs. 1.235 logMAR, p = 0.04) eyes. Outreach by a telehealth extender reached 62 patients (59%), 43 through family members or healthcare proxies. Half of the cases where a proxy was contacted revealed that the patient in question had died. Among those contacted directly, one third expressed willingness to resume eye care (20 patients), with 11 scheduling appointments (55%). Despite only two patients returning for in‐person eye care through the intervention, the LTFU rate halved to 4.4% by accounting for those patients who no longer needed eye care at the practice.ConclusionsThere is a substantial risk that older patients with advanced AMD will become LTFU. Targeted telephone outreach can provide a pathway for vulnerable patients to return to care.
Getting what you expect: How civil servant stereotypes affect citizen satisfaction and perceived performance
Authors: Bertram Isa , Bouwman Robin , Tummers Lars 
Published: March 2024

AbstractThis study tests whether civil servant stereotypes affect how citizens experience public service delivery. Using a pre‐registered survey vignette experiment (n = 1130), we activate civil servant stereotypes (negative, positive, or control) and assess whether this affects subsequent perceptions and evaluations of public services. Results indicate that stereotypes shape experiences, with the activation of negative stereotypes leading to lower levels of satisfaction and perceived performance, compared to positive stereotype activation and control. These findings emphasize that negative civil servant stereotypes can have problematic consequences, and contribute to our understanding of the commonly used Expectancy Disconfirmation Model in citizen satisfaction research.
Invisible and indispensable: Using the lowly request for proposals to advance public value
Authors: Merrick Weston , Bernardy Pete , Carter Patrick 
Published: March 2024

AbstractRequests for Proposals (RFP) may be the pinnacle of bureaucratic mundanity. Yet, hidden within this apparent monotony are powerful tools to advance public values. Federal, state, and local government grants deploy staggering sums, reaching into the hundreds of billions of dollars annually. With these distributions, the executive branch is often delegated substantial discretion. These are choices of consequence, but little support exists for public managers tasked with this work. This article examines the potential to improve administrative decision‐making by enhancing our understanding of how discretion is authorized and applied regarding RFPs. Drawing from professional experience, we create a framework to identify dimensions of discretion in these proposals and apply it to a Minnesota case. We end with a call for academics and practitioners to better partner on empirical inquiry that improves RFP administration; in doing so, there is immense potential to help civil servants to improve outcomes for the public.
Role of beta-hydroxybutyrate measurement in the evaluation of plasma glucose concentrations in newborn infants
Authors: Stanley Charles A , Weston Philip J , Harris Deborah L , De León Diva D , Harding Jane E 
Published: March 2024

ObjectiveThe Glucose in Well Babies (GLOW) Study showed that there are two phases of low glucose concentrations in healthy newborn infants: an initial phase in which plasma concentrations of ketones are low; and a second phase in which low glucose concentrations are accompanied by elevated concentrations of ketones. The implications of these two phases for the brain differ depending on whether ketones are available as alternative substrate for brain metabolism. The purpose of this study was to estimate the duration of these two phases of neonatal low glucose concentrations in 66 healthy breastfed newborns from the GLOW Study during the first 5 days of life.MethodsThe sum of glucose and beta-hydroxybutyrate (BOHB) was used as a proxy for the total concentrations of insulin-dependent fuels for the brain; a threshold value below 4 mmol/L was taken to indicate the presence of relative hyperinsulinism and a BOHB concentration above 0.5 mmol/L to indicate ketonaemia.ResultsThe first phase of low glucose concentrations lasted a median of 40 hours and in 15% of infants, this persisted beyond 60 hours. Fifty (76%) of the 66 infants subsequently had ketonaemia, which resolved at a median age of 76 hours (range 41–>120 hours).ConclusionsThese data suggest that monitoring BOHB concentrations may be useful for interpreting glucose concentrations in newborns and screening for persistent hyperinsulinism.
Abstract A002: In-silico screening of race-specific endometrial cancer methylation markers using machine learning techniques
Authors: Asif Huma , Foley Grace , Kim Julie 
Published: March 2024

Abstract
Targeted molecular therapy is a promising strategy for cancer treatment. Despite the benefits of these therapies, racial disparities in cancer therapy efficacy persist. To close this racial gap, there is a need to find race-specific biomarkers at the molecular level. Since abnormal DNA methylation has been linked with cancer and has a great potential to transform the diagnosis and treatment of cancer, the main objective of this study was to combine differential DNA methylation and machine learning techniques to identify race-specific methylation signature biomarkers in endometrial tumor samples from White and Black women. We performed genome wide Differentially Methylated CpG (DMCs) analysis in tumors from White patients (TWP) samples compared to tumors from Black patients (TBP) samples using Endometrial Carcinoma (EC) methylation and clinical data from The Cancer Genome Atlas (TCGA). We used supervised and unsupervised machine learning techniques to filter and select signature biomarkers. To evaluate the prognostic capacity of these genes, we performed univariate and multivariate survival analyses using Cox proportional hazards regression model from survival R package. By combining differential methylation CpGs and machine learning techniques, we reduced 704 differentially methylated CpGs to reliable race-specific epigenetic signature genes (ESGs) and Core- epigenetic signature genes (core-ESGs). An area under the curve (AUC) of 0.98 was achieved based on these signature genes. We further found that ESGs showed statistically significant overall survival differences between two racial groups. In addition, comparison of the mutational landscape showed differences in mutation frequencies in the ESGs between the two groups. By combining differential methylation analysis and machine learning techniques, we identified novel race-specific epigenetic signature genes in Black and White women with endometrial cancer. We further showed the potential of these gene in predicting survival differences, mutation, and transcriptomic differences in Black and White women. We propose that combined methylation and somatic mutation profiling of these novel race-specific signature genes can be used to develop potential therapeutic targets for diagnosis and treating endometrial cancer.
Citation Format: Huma Asif, Grace Foley, Julie Kim. In-silico screening of race-specific endometrial cancer methylation markers using machine learning techniques [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A002.
Abstract A012: Genomic landscape of somatic alterations identified in endometrial cancer using liquid biopsy
Authors: Drusbosky Leylah , Haynes Ginger , Grant Brooke , Sobernis Pamela , Lheureux Stephanie 
Published: March 2024

Abstract
Background: With advances in understanding the biology of endometrial cancer, molecular sub-groups have been defined to assess prognosis and guide treatment decisions. This classification is based on surrogate markers in archival paraffin-embedded tissues. The landscape of somatic alterations as detected by liquid biopsy has not been well described in advanced endometrial cancer. Methods: A retrospective analysis was performed using de-identified genomic data collected from patients with advanced endometrial cancer who underwent liquid biopsy testing with a 74-83 gene panel as part of clinical care (Guardant360, Guardant Health, Inc.). Results: 1,988 females with a median age of 68 [range 23-95] years were included in the analysis. 45% of patients were tested at diagnosis of advanced disease; 43% were tested at time of disease progression. 91.6% of patients had ≥1 somatic alteration detected and 12% of patients were MSI-High. The most frequently altered genes included TP53 (65%), PIK3CA (31%), PTEN (27%), ARID1A (24%), like prior reports of genomic alterations detected in tissue samples. CCNE1 amplifications were enriched in 11% of samples with TP53 alterations (p&lt;0.0001; q&lt;0.0001) and EGFR amplifications were enriched in samples without TP53 alterations (p&lt;0.0001; q&lt;0.0001). MSI-H samples were enriched for alterations in ARID1A, PTEN, PIK3CA, ATM, MSH6 and others, while samples without MSI were enriched for alterations in TP53 and CCNE1 (p&lt;0.0001; q&lt;0.0001). Oncogenic fusions were rare in this cohort (0.2%) and included FGFR1 and FGFR3 rearrangements. Activating, druggable alterations were identified in PIK3CA, KRAS, ERBB2, and BRCA1/2. Putative pathogenic germline alterations were detected in 61 (3%) patients and included ATM (18%), BRCA1 (33%), BRCA2 (21%), and lower frequencies of CHEK2, FANCA, MLH1, MSH2, MSH6, and PALB2. Conclusions: While descriptive in nature, this analysis is the largest cohort of advanced endometrial cancer analyzed using a clinically available liquid biopsy assay and demonstrates the feasibility of somatic alteration detection. This report paves the way for using liquid biopsy as a potential tool for guiding targeted chemotherapeutic strategies.
Citation Format: Leylah Drusbosky, Ginger Haynes, Brooke Grant, Pamela Sobernis, Stephanie Lheureux. Genomic landscape of somatic alterations identified in endometrial cancer using liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A012.
Abstract A019: Autologous patient-derived organoid-immune cell co-culture platform for therapeutics discovery in high-grade endometrial cancer
Authors: Chung Charlie , Nizam Aaron , Yueh Brian , Subhash Santhilal , Frimer Marina , Goldberg Gary L. , Beyaz Semir 
Published: March 2024

Abstract
Endometrial cancer is the most common gynecologic malignancy with increasing incidence and mortality rates. Recurrent endometrial cancers, which are mostly from high-grade endometrial cancers (HGEC), have limited treatment options and display extremely poor response rate upon chemotherapies, thus showing very poor prognosis. Immunotherapy revolutionized the field of cancer medicine, but lack of scalable and sustainable pre-clinical models for HGEC poses a significant challenge in studying critical immunological aspects of HGEC. We therefore established a comprehensive endometrial cancer biobank comprising primary tissues, patient-derived organoids (PDO), and their matching immune cells from all existing HGEC types, enabling us to establish an autologous interaction between cancer and immune cells in vitro. Inactivation of antigen processing and presentation (APP) pathways is one of the major mechanisms for immune evasion in many cancer types including HGEC. Using a subset of our biobank, we performed bulk RNA-seq on 11 normal-cancer PDO pairs and found that genes involved in APP pathways, MHC-II in particular, are downregulated in HGEC organoids. We found that dampened MHC expression can be reverted by external stimuli such as IFNγ and Tazemetostat. We then assessed the effects of enhanced MHC-I and -II expression mediated by the two molecules on cancer-immune cell interactions by setting up organoid-immune cell co-cultures using autologous PBMC, CD4, and CD8 T cells. Our results suggest that cell signaling and epigenetic manipulations on HGEC can be exploited to enhance immune cell-mediated apoptosis. Using our co-culture platform, we next evaluated the efficacy of different immunotherapeutic modalities such as NK cell transfer, bi-specific T-cell engagers, and CAR-T cells on HGEC. Our proof-of-principle experiments demonstrate the utility of our co-culture system in studying the autologous cancer-immune cell interactions from the same patient ex vivo. Our sustainable and scalable testing platform could be used to assess the safety and efficacy of current therapeutics or to identify new therapeutics that enhance immune responses against advanced cancers lacking effective treatment options such as HGEC.
Citation Format: Charlie Chung, Aaron Nizam, Brian Yueh, Santhilal Subhash, Marina Frimer, Gary L. Goldberg, Semir Beyaz. Autologous patient-derived organoid-immune cell co-culture platform for therapeutics discovery in high-grade endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A019.
Abstract A022: Detecting cardiovascular disease risk in early-stage endometrial cancer survivors: preliminary evidence of pulse wave velocity and social vulnerability index
Authors: Bates-Fraser Lauren C. , Bae-Jump Victoria , Stoner Lee , Hanson Erik D. 
Published: March 2024

Abstract
BACKGROUND: Endometrial cancer survivors (ECS) experience high rates of cardiovascular disease (CVD) likely due to lifestyle and social-environmental factors, including high obesity rates up to 60%. Early detection of CVD is crucial in order to intervene; however, strategies to identify ECS most at risk for CVD are currently lacking. The gold-standard methodology to non-invasively measure CVD is pulse wave velocity (PWV), and one way to identify social-environmental susceptibility is the Centers for Disease Control social vulnerability index (SVI). PURPOSE: Therefore, the purpose of this study is to investigate (1) CVD risk in stage 1 ECS using PWV and (2) the social-environmental influence on CVD risk using SVI. METHODS: Stage 1 ECS who were 1-12 months post-treatment, with a BMI ≥ 25.0 kg/m2, age 50-80 years, and English speaking were recruited in the gynecology-oncology clinic. Oscillometric PWV was measured in a supine position via Mobil-O-Graph. Body composition [body fat percentage (%)] was measured via Bioelectrical Impedance Analysis. Participant zip code was used to determine SVI of their county of residence. SVI is defined as low-medium (0.00-0.49), medium-high (0.50-0.69), and high (0.70-1.00). Linear regression was used to compare PWV and SVI. RESULTS: Seventeen ECS (65% White, 25% Black, 5% Asian, 5% American Indian, 64 ± 7 years old, 6 ± 4 months post-treatment, 44 ± 6% body fat) participated in the study. Participants resided in counties with low-medium (18%), medium-high (24%), and high (58%) SVI and PWV was measured as 8.2 ± 0.8 m/s, 9.1 ± 0.8 m/s, and 9.7 ± 1.0 m/s respectively. The overall regression was not statistically significant (R=0.38, R2=0.14, F=1.15, p=0.34). DISCUSSION: Overall, PWV was elevated in ECS residing in counties with medium-high and high SVI categories compared to normative data. PWV can be used to non-invasively measure CVD risk in clinic in early-stage ECS. Despite failing to reach statistical significance, a 1.0 m/s change is considered to be a clinically meaningful difference in PWV. Therefore, ECS residing in counties with high SVI may be at greater CVD risk compared to those living in less vulnerable communities. Further research is needed, including a larger sample size, to identify successful interventions to reduce CVD in ECS most at risk.
Citation Format: Lauren C. Bates-Fraser, Victoria Bae-Jump, Lee Stoner, Erik D. Hanson. Detecting cardiovascular disease risk in early-stage endometrial cancer survivors: preliminary evidence of pulse wave velocity and social vulnerability index [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A022.
Abstract A023: Assessing the reproducibility crisis in vaginal microbiome studies for clinical applications in endometrial cancer
Authors: Dodani Dollina D. , Talhouk Aline 
Published: March 2024

Abstract
Recent associations between vaginal microbiota and gynecological cancer have led to high-throughput sequencing datasets identifying diagnostic biomarkers for Endometrial Cancer (EC). However, lack of bioinformatics standards results in inconsistent independent studies with poor reproducibility, making them clinically inapplicable. This study leverages publicly available amplicon sequence data to address the reproducibility of EC microbiome studies. We implemented bioinformatics pipelines from five studies to reproduce and measure the replicability of published results across cohorts using metrics such as alpha diversity, beta diversity and differentially expressed taxa. We further evaluated separability between benign and cancer patients at different taxonomic levels (phylum, class, order, family, and genus) within and across datasets using boosted tree classifiers and Area Under the Curve (AUC) as the performance metric. While we reproduced the general trend of observing higher microbial diversity in EC compared to healthy controls, we found irregularities in two cohorts. Using beta diversity distance metrics, we identified that histology alone explains less than 3% of the variance in all cohorts. Three microbiome differential abundance methods were used in the five studies. While they all agree on a decrease in the Lactobacillus genus in EC patients, there is no consensus on other taxa associated with EC. We also found that separability between benign and cancerous conditions is highest at the class level, having an AUC score of 0.86. In subsequent steps, we will perform an integrative analysis to identify an EC vaginal microbiome predictive signature that is preserved across all five cohorts, benefiting screening programs.
Citation Format: Dollina D. Dodani, Aline Talhouk. Assessing the reproducibility crisis in vaginal microbiome studies for clinical applications in endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A023.
Abstract IA015: Epigenetic approaches for endometrial cancer
Authors: Zhang Rugang 
Published: March 2024

Abstract
The past decade has brought unprecedented progress in understanding the genetics of endometrial cancer, but cures remain elusive due to the lack of insights into mechanisms that can be leveraged to develop new therapies. Endometrial cancer is genetically heterogeneous and, therefore, it is imperative that therapeutic strategies become personalized by targeting distinct molecular subsets of endometrial cancer. Despite the importance of epigenetic regulators in endometrial cancer, the mechanism of action for these epigenetic regulators and the associated vulnerabilities exposed by their dysregulations have remained elusive for most of them. Here we will discuss our recent work on how to leverage epigenetic mechanisms to address unmet clinical needs in endometrial cancer through integrated approaches.
Citation Format: Rugang Zhang. Epigenetic approaches for endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA015.
Abstract IA017: Spontaneous humoral responses in endometrial cancer provide a rationale for novel tumor-penetrating therapeutic antibodies
Authors: Conejo-Garcia Jose R. 
Published: March 2024

Abstract
The role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different histological subtypes of endometrial carcinoma, we found that concomitant accumulation of T, B, and plasma cells at tumor beds predicted better survival. However, only B cell markers corresponded with prolonged survival specifically in high-grade endometrioid type and serous tumors. Immune protection was associated with class-switched IgA and, to a lesser extent, IgG. Expression of polymeric immunoglobulin receptor (PIGR) by tumor cells allow dimeric IgA transcytosis. Taking advantage of tumor cell penetration, we demonstrated that mutation-specific dIgA, but not IgG, neutralized KRASG12D inside carcinoma cells and expelled this oncodriver (but not wild-type KRAS) outside tumor cells, abrogating tumor cell proliferation in an antigen-specific manner. Accordingly, KRASG12D-specific dIgA1, but not the same antibody on an IgG backbone, abrogated KRASG12D carcinoma growth in vivo, more effectively than small molecule KRASG12D inhibitors, including in syngeneic tumor-bearing immunocompetent mice. Because &gt;6% of endometrial cancers exhibit KRAS mutations, our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target intracellular oncogenes, which could be applicable to many aggressive and frequent human cancers.
Citation Format: Jose R. Conejo-Garcia. Spontaneous humoral responses in endometrial cancer provide a rationale for novel tumor-penetrating therapeutic antibodies [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA017.