bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Subtypes of High-Grade Serous Ovarian Cancer across Racial Groups and Gene Expression Platforms
Authors: Davidson Natalie R. , Barnard Mollie E. , Hippen Ariel A. , Campbell Amy , Johnson Courtney E. , Way Gregory P. , Dalley Brian K. , Berchuck Andrew , Salas Lucas A. , Peres Lauren C. , Marks Jeffrey R. , Schildkraut Joellen M. , Greene Casey S. , Doherty Jennifer A. 
Published: May 2024

Abstract

Background:
High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may contribute to poorer HGSC survival among Black versus White individuals.

Methods:
We included newly generated RNA sequencing data from Black and White individuals and array-based genotyping data from four existing studies of White and Japanese individuals. We used K-means clustering, a method with no predefined number of clusters or dataset-specific features, to assign subtypes. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. After mapping to The Cancer Genome Atlas–derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset.

Results:
Cluster-specific gene expression was similar across gene expression platforms and racial groups. Comparing the Black population with the White and Japanese populations, the immunoreactive subtype was more common (39% vs. 23%–28%) and the differentiated subtype was less common (7% vs. 22%–31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA sequencing data; compared with mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases [Black population HR = 0.79 (0.55, 1.13); White population HR = 0.86 (0.62, 1.19)].

Conclusions:
Although the prevalence of HGSC subtypes varied by race, subtype-specific survival was similar.

Impact:
HGSC subtypes can be consistently assigned across platforms and self-identified racial groups.
PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J. 
Published: May 2024

Abstract
Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast cancer cells without functional p53. In vitro the combination increased DNA damage and apoptosis. In palbociclib-resistant, TP53 mutant PDX-derived organoids and PDXs, RP-6306 with low-dose gemcitabine induced greater tumor volume reduction compared to treatment with either single agent. Our study demonstrates the clinical potential of RP-6306 in combination with gemcitabine for ET and CDK4/6 inhibitor resistant TP53 mutant ER+ breast cancer.
Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis
Authors: Harrington Josephine , Hellkamp Anne S. , Mahaffey Kenneth W. , Breithardt Günter , Halperin Jonathan L. , Hankey Graeme J. , Becker Richard C. , Nessel Christopher C. , Berkowitz Scott D. , Fox Keith A. A. , Singer Daniel E. , Goodman Shaun G. , Patel Manesh R. , Piccini Jonathan P. 
Published: May 2024

Background
Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations.

Methods and Results

ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double‐blind, double‐dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator‐reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (
P
=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively,
P
=0.88).

Conclusions
DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.
Early Alteration of Right Ventricle–Pulmonary Artery Coupling in Experimental Heart Failure With Preserved Ejection Fraction
Authors: Hubesch Géraldine , Dewachter Céline , Chomette Laura , Hupkens Emeline , Jespers Pascale , Vegh Grégory , Doppler Mathilde , Sheikh Mohammad Umair , Thiriard Anaïs , Remmelink Myriam , Vachiéry Jean‐Luc , McEntee Kathleen , Dewachter Laurence 
Published: May 2024

Background
Pulmonary hypertension and right ventricular (RV) dysfunction are major prognostic determinants in patients with heart failure with preserved ejection fraction (HFpEF). The underlying pathomechanisms remain unknown. In this context, we sought to study the pathogenesis of pulmonary hypertension and RV dysfunction in a rat model of obesity‐associated HFpEF.

Methods and Results
HFpEF was induced in obesity‐prone rats fed a high‐fat diet (n=13) and compared with obesity‐resistant rats fed with standard chow (n=9). After 12 months, the animals underwent echocardiographic and hemodynamic evaluation followed by tissue sampling for pathobiological assessment. HFpEF rats presented mild RV pressure overload (with increased RV systolic pressure and pulmonary vascular resistance). No changes in pulmonary artery medial thickness and ex vivo vasoreactivity (to acetylcholine and endothelin‐1) were observed and RNA sequencing analysis failed to identify gene clustering in HFpEF lungs. However, released nitric oxide levels were decreased in HFpEF pulmonary artery, while lung expression of preproendothelin‐1 was increased. In HFpEF rats, RV structure and function were altered, with RV enlargement, decreased RV fractional area change and free wall longitudinal fractional shortening, together with altered right ventricle–pulmonary artery coupling (estimated by tricuspid annular plane systolic excursion/systolic pulmonary artery pressure). Hypertrophy and apoptosis (evaluated by transferase biotin‐ dUTP nick‐end labeling staining) were increased in right and left ventricles of HFpEF rats. There was an inverse correlation between tricuspid annular plane systolic excursion/systolic pulmonary artery pressure and RV apoptotic rate. Plasma levels of soluble suppression of tumorigenicity‐2, interleukin‐1β, ‐6 and ‐17A were increased in HFpEF rats.

Conclusions
Obesity‐associated HFpEF in rats spontaneously evolves to pulmonary hypertension–HFpEF associated with impaired right ventricle–pulmonary artery coupling that appears disproportionate to a slight increase in RV afterload.
Saccular and Fusiform Abdominal Aortic Aneurysms Treated With Endovascular Repair Differ in Presentation and Treatment Threshold: Analyses Using a National Clinical Database in Japan
Authors: Ozawa Hirotsugu , Takahashi Arata , Bessho Ryuzo , Hoshina Katsuyuki , Shukuzawa Kota , Ohki Takao 
Published: May 2024

Background
Saccular abdominal aortic aneurysms (AAAs) are considered to be at higher risk of rupture than fusiform AAAs, but not much is known about the extent of this risk. Therefore, this study aimed to compare the rupture presentation between fusiform and saccular AAAs.

Methods and Results

This is a retrospective cohort study on 27 290 patients who underwent primary endovascular repair for a degenerative AAA between 2016 and 2019, and who were registered in the National Clinical Database in Japan. At operation for nonruptured case, the aneurysm diameter was significantly smaller in saccular AAAs than in fusiform AAAs (median, 44.0 versus 51.0 mm;
P
<0.001). Similarly, aneurysm diameter at rupture was significantly smaller in saccular AAAs than in fusiform AAAs (median, 55.6 versus 68.0 mm;
P
<0.001). The likelihood of repair for rupture was significantly higher in saccular AAAs than in fusiform AAAs in the 40‐ to 54‐mm diameter range, in which saccular morphology was found to be an independent risk factor for rupture against fusiform morphology by adjusting for sex and aneurysm diameter (odds ratio, 2.54 [95% CI, 1.75–3.69]). In addition, receiver‐operating characteristic curve analysis revealed that the cutoff diameter to predict rupture was smaller in saccular AAAs than in fusiform AAAs (50.5 and 59.5 mm, respectively) based on the Youden index.

Conclusions
Saccular AAAs presented at smaller diameters than fusiform AAAs in patients with ruptured AAAs treated with endovascular aortic repair, which supports the idea that saccular AAAs should be treated at smaller diameters.
Racial and Ethnic Disparities in Health Care Usage and Death by Neighborhood Poverty Among Individuals With Congenital Heart Defects, 4 US Surveillance Sites, 2011 to 2013
Authors: Raskind‐Hood Cheryl L. , Kancherla Vijaya , Ivey Lindsey C. , Rodriguez Fred H. , Sullivan Anaclare M. , Lui George K. , Botto Lorenzo , Feldkamp Marcia , Li Jennifer S. , D'Ottavio Alfred , Farr Sherry L. , Glidewell Jill , Book Wendy M. 
Published: May 2024

Background
Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described.

Methods and Results

Individuals aged 1 to 64 years, with at least 1 CHD‐related
International Classification of Diseases, Ninth Revision, Clinical Modification
(
ICD‐9‐CM
) code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites. Residence was classified into lower‐ or higher‐poverty neighborhoods on the basis of zip code tabulation area from the 2014 American Community Survey 5‐year estimates. Multivariable logistic regression models, adjusting for site, sex, CHD anatomic severity, and insurance‐evaluated associations between race and ethnicity, and health care usage and death, stratified by neighborhood poverty. Of 31 542 individuals, 22.2% were non‐Hispanic Black and 17.0% Hispanic. In high‐poverty neighborhoods, non‐Hispanic Black (44.4%) and Hispanic (47.7%) individuals, respectively, were more likely to be hospitalized (adjusted odds ratio [aOR], 1.2 [95% CI, 1.1–1.3]; and aOR, 1.3 [95% CI, 1.2–1.5]) and have emergency department visits (aOR, 1.3 [95% CI, 1.2–1.5] and aOR, 1.8 [95% CI, 1.5–2.0]) compared with non‐Hispanic White individuals. In high poverty neighborhoods, non‐Hispanic Black individuals with CHD had 1.7 times the odds of death compared with non‐Hispanic White individuals in high‐poverty neighborhoods (95% CI, 1.1–2.7). Racial and ethnic disparities in health care usage were similar in low‐poverty neighborhoods, but disparities in death were attenuated (aOR for non‐Hispanic Black, 1.2 [95% CI=0.9–1.7]).

Conclusions
Racial and ethnic disparities in health care usage were found among individuals with CHD in low‐ and high‐poverty neighborhoods, but mortality disparities were larger in high‐poverty neighborhoods. Understanding individual‐ and community‐level social determinants of health, including access to health care, may help address racial and ethnic inequities in health care usage and death among individuals with CHD.
Ten‐Year Risk Equations for Incident Heart Failure in Established Atherosclerotic Cardiovascular Disease Populations
Authors: Dawson Luke P. , Carrington Melinda J. , Haregu Tilahun , Nanayakkara Shane , Jennings Garry , Dart Anthony , Stub Dion , Inouye Michael , Kaye David 
Published: May 2024

Background
Ten‐year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly prevalent in HF cohorts. This study aimed to develop and validate 10‐year risk equations for incident HF in patients with known ASCVD.

Methods and Results
Ten‐year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006–2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000–2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow‐up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow‐up 9.4±3.7 years). Predictors of HF included in the sex‐specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD‐HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations.

Conclusions
ASCVD‐specific 10‐year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD‐HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high‐risk group.
Improving Probability-based Prompt Selection Through Unified Evaluation and Analysis
Authors: Yang Sohee , Kim Jonghyeon , Jang Joel , Ye Seonghyeon , Lee Hyunji , Seo Minjoon 
Published: May 2024

Abstract
Previous work in prompt engineering for large language models has introduced different gradient-free probability-based prompt selection methods that aim to choose the optimal prompt among the candidates for a given task but have failed to provide a comprehensive and fair comparison between each other. In this paper, we propose a unified framework to interpret and evaluate the existing probability-based prompt selection methods by performing extensive experiments on 13 common and diverse NLP tasks. We find that each of the existing methods can be interpreted as some variant of the method that maximizes mutual information between the input and the predicted output (MI). Utilizing this finding, we develop several other combinatorial variants of MI and increase the effectiveness of the oracle prompt selection method from 87.79% to 94.98%, measured as the ratio of the performance of the selected prompt to that of the optimal oracle prompt. Furthermore, considering that all the methods rely on the output probability distribution of the model that might be biased, we propose a novel calibration method called Calibration by Marginalization (CBM) that is orthogonal to the existing methods and helps increase the prompt selection effectiveness of the best method to 96.85%, achieving 99.44% of the oracle prompt F1 without calibration.1
Lizard abundance in forest fragments: effects of patch size, patch shape, thermoregulation, and habitat quality
Authors: Díaz José A. , Santos Tomás , Llanos-Garrido Alejandro 
Published: May 2024

Abstract
The effects of forest fragmentation on ecosystems are pervasive, but little is known about the factors that influence lizard abundance in fragmented landscapes. We studied the roles of patch size and shape, thermal quality, and refuge availability as predictors of the relative abundance of Psammodromus algirus lizards at deciduous or evergreen forest fragments surrounded by cereal fields. Relative abundance, based on time-controlled counts, decreased from the northeast (dominated by deciduous habitat) to the southwest (with a higher cover of croplands, and dominated by evergreen habitat). Refuge availability was correlated with this gradient, decreasing from the northeast to the southwest and being larger in deciduous than in evergreen fragments. After controlling for the effects of this environmental variation, lizard abundance increased as perimeter-to-area ratio (P/A) decreased (and consequently as fragment size increased). Although the effects of thermal quality as such were negligible, our results can be interpreted in the light of thermoregulatory requirements; given the low temperatures available at shaded locations, lizards should actively select sunlit patches while they try to minimize predation risk by basking as close as possible to the nearest refuge. Although use of fragment edges as basking sites is expected to increase with P/A ratio, lizards should avoid using them as basking sites, because both exposure to predators and risk of overheating are expected to be higher at edges and croplands than inside fragments. We conclude that long and narrow forest strips with high P/A ratios could act as ecological traps rather than as dispersion-promoting corridors.
Disparities in Smoking and Heavy Drinking Behaviors by Disability Status and Age of Disability Onset: Secondary Analysis of National Health Interview Survey Data
Authors: Sarmiento Cristina A. , Furniss Anna , Morris Megan A. , Stransky Michelle L. , Thompson Darcy A. 
Published: May 2024

Objectives: People with childhood-onset disabilities are living into adulthood, and the prevalence of smoking and illicit drug use among adults with disabilities is high. We evaluated the relationship between disability status and age of disability onset, current cigarette smoking status, and heavy alcohol drinking. Methods: We conducted a secondary data analysis of the National Health Interview Survey (NHIS), a US survey on illness and disability. Among 2020 NHIS participants aged 22-80 years (n = 28 225), we compared self-reported prevalence of current cigarette smoking and heavy alcohol drinking among those with and without disabilities and among those with childhood- versus adult-onset disabilities. We used adjusted logistic regression analysis to calculate the adjusted odds ratios (AORs) of current smoking and heavy alcohol drinking based on disability status and age of disability onset. Results: Compared with adults without disabilities, adults with disabilities were significantly more likely to report current smoking (23.5% vs 11.2%; P < .001) and significantly less likely to report heavy alcohol drinking (5.3% vs 7.4%; P = .001). The prevalence of these behaviors did not vary significantly by age of disability onset. In adjusted logistic regression models, adults with disabilities had significantly higher odds of current smoking (AOR = 1.76; 95% CI, 1.53-2.03) and similar odds of heavy alcohol drinking (AOR = 0.82; 95% CI, 0.65-1.04) compared with adults without disabilities. The odds of these health behaviors did not vary significantly by age of disability onset. Conclusions: Adults with disabilities overall may be at high risk for these unhealthy behaviors, particularly smoking, regardless of age of disability onset. Routine screening and cessation counseling related to smoking and unhealthy alcohol use are important for all people with disabilities.
Utility of abbreviated MRI in the post-treatment evaluation of rectal cancer
Authors: Park Sungeun , Park Hee Sun , Jang Siwon , Cho Jungheum , Kim Jae Hyun , Yu Mi Hye , Jung Sung Il , Kim Young Jun , Hwang Dae-Yong 
Published: May 2024

Background Post-treatment evaluation of patients with rectal cancer (RC) using magnetic resonance imaging (MRI) burdens medical resources, necessitating an exploration of abbreviated protocols Purpose To evaluate the diagnostic performance of abbreviated MRI (A-MRI) for the post-treatment evaluation of RC patients. Material and Methods This retrospective study included RC patients who underwent non-contrast rectal MRI and standard liver MRI, as well as abdominal contrast-enhanced computed tomography (CECT) for post-treatment evaluation. A-MRI comprised diffusion-weighted imaging (DWI) and T2-weighted imaging of the upper abdomen and the pelvic cavity. Three radiologists independently reviewed A-MRI, CECT, and standard liver MRI in the detection of viable disease. The diagnostic performances were compared using a reference standard considering all available information, including pathology, FDG-PET, endoscopic results, and clinical follow-up. Results We included 78 patients (50 men, 28 women; mean age=60.9 ± 10.2 years) and observed viable disease in 34 (43.6%). On a per-patient-basis analysis, A-MRI showed significantly higher sensitivity (95% vs. 81%, P = 0.04) and higher accuracy (93% vs. 82%, P < 0.01), compared to those of CECT, while A-MRI showed comparable sensitivity (91% vs. 91%, P = 0.42) and accuracy (97% vs. 98%, P = 0.06) to that of standard liver MRI. On a per-lesion-based analysis, A-MRI exhibited significantly superior lesion detectability than that of CECT (figure of merit 0.91 vs. 0.77, P < 0.01) and comparable to that of standard liver MRI (figure of merit 0.91 vs. 0.92, P = 0.75). Conclusion A-MRI exhibited higher sensitivity and diagnostic accuracy than those of CECT in the post-treatment evaluation of RC, while it showed comparable performances with standard liver MRI. A-MRI provides diagnostic added value in the follow-up of RC patients.