bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Treatment Response of Patients With Major Depressive Disorder to Selective Serotonin Reuptake Inhibitors Using Machine Learning Techniques and EEG Functional Connectivity Features
Authors: Wang Fanglan , You Zifan , Zhang Tingkai , Xu Kai , Wang Liangliang , He Jingqi , Tang Jinsong 
Published: January 2025

Background: Escitalopram and sertraline are first‐line medications for treating depression. They belong to selective serotonin reuptake inhibitors (SSRIs) and are widely used due to their effectiveness and fewer side effects. However, despite the significant efficacy of escitalopram and sertraline, there is a large variation among individuals. Therefore, predicting symptom improvement based on the baseline period is crucial.Methods: In this study, we conducted functional connectivity (FC) analysis of electroencephalogram (EEG) data during resting‐state with eyes closed, resting‐state with eyes open, watching neutral videos, negative videos, and comedy videos for 30 untreated depression patients over 2 weeks. Each modality yielded 18 EEG FC features. Based on the treatment response at 8 weeks, patients were divided into treatment‐effective and treatment‐ineffective groups. The dataset was randomly split into a 75% training set and a 25% independent test set. Feature selection was performed on these FC features in the training set, and the selected features were used to classify the effective and ineffective groups using the support vector machine (SVM) machine learning algorithm. Fivefold cross‐validation was conducted on the training set to obtain validation results, followed by testing on the test set. The Spearman’s correlation method was used to analyze the correlation between each EEG feature value and the reduction rate of the Hamilton Depression Rating Scale for Depression (HAMD‐17) scores from baseline to 8 weeks, with Bonferroni correction applied.Results: The study found that out of all modalities, 33 features achieved classification accuracies of over 95% on the validation set, and two features achieved classification accuracies of over 85% on the independent test set. A total of 58 feature values were found to be correlated with the reduction rate of HAMD‐17 scores from baseline to 8 weeks.Conclusions: The findings from this research suggest that EEG FC features at baseline can be used to differentiate between effective and ineffective groups with high accuracy using machine learning models. Multiple feature values and HAMD‐17 scores were found to be correlated with the reduction rate of HAMD‐17 scores from baseline to 8 weeks, and these correlated feature values can be used to predict treatment efficacy.Trial Registration: ClinicalTrials.gov identifier: NCT05775809
Positive Islet Cell Cytoplasmic Antibody and Long‐Term Use of Lipid‐Lowering Agents Are Positively Correlated With Peripheral Atherosclerosis in Patients With Autoimmune Diabetes: A Cross‐Sectional Study
Authors: Chen Xinyue , Yu Jie , Liu Yiwen , Wang Xuechen , Ping Fan , Li Wei , Zhang Huabing , Xu Lingling , Li Yuxiu 
Published: January 2025

Aims: This cross‐sectional study is aimed at determining whether systemic inflammation, diabetic autoantibodies, and islet β cell dysfunction play a role in the progression of macrovascular complications in patients with autoimmune diabetes.Methods: 202 patients with autoimmune diabetes aged ≥ 35 years and hospitalized in Peking Union Medical College Hospital were enrolled in this study. The patients were divided into three groups based on the severity of peripheral atherosclerosis. Biomarkers of systemic inflammation, diabetes autoantibodies, islet β cell function, and other covariates validated to be associated with macrovascular complications were collected. Correlations between the severity of peripheral atherosclerosis and systemic inflammation, diabetic autoantibodies, and islet β cell function were examined using an ordinal logistic regression model.Results: Of the enrolled patients, 39.1% were male, with a median age of 53 (43, 60) years and a diabetes duration of 96 (36, 216) months. 58 patients had no lesions in the peripheral arteries, 72 had atherosclerosis in the carotid or lower extremity arteries, and the rest had lesions in both arteries. In the multifactor ordinal logistic regression test, positive islet cell cytoplasmic antibody (ICA) and long‐term use of lipid‐lowering agents were independently associated with peripheral atherosclerosis after adjusting for age and diabetes duration.Conclusions: The correlation between positive ICA and atherosclerosis suggests inflammation at an early stage plays a role in macrovascular complications in autoimmune diabetes. The association between long‐term use of lipid‐lowering agents and atherosclerosis suggests the need for early screening and intervention for dyslipidemia in patients with autoimmune diabetes.
A Theoretical Model of Clinical Nurses’ Intentions to Stay During Disasters: A Structural Equation Modeling Approach
Authors: Shin Hyerine , Kim Kyunghee , Lee Suk Jeong , Hyun Park So , Lim Changwon , Kim Hyun Jun , Kim Ji-Su 
Published: January 2025

Background: With the increasing frequency and severity of disasters, retaining skilled nurses is essential for sustaining healthcare systems in times of crisis. Given that behavior is largely influenced by intention, a predictive model for nurses’ intent to stay (ITS) is needed.Aim: This study aimed to develop and validate a comprehensive structural model explaining clinical nurses’ ITS during disasters. This model addresses the critical need to understand and enhance nurse retention during crises.Methods: In this cross‐sectional study, 549 nurses who worked during the COVID‐19 pandemic participated. The data were collected through a web‐based self‐report survey from March 5 to 15, 2024. Factor analysis, model fit confirmation, and path significance were analyzed using SPSS/WIN 23.0 and AMOS 28.0. A two‐step approach was employed to validate the hypothetical model.Results: Group cohesion significantly impacted organizational commitment, empowerment, and job satisfaction. Adequate staffing and resources were crucial in influencing moral distress and organizational commitment. Both job satisfaction and organizational commitment directly affected the ITS, with group cohesion exerting an indirect effect. Path analysis demonstrated that adequate staffing and resources notably influenced organizational commitment, while adaptive leadership, adequate staffing, and disaster nursing competency significantly impacted job satisfaction. The model explained 71.4% of the variance in nurses’ intention to stay during disasters.Conclusion: The study highlights that organizational commitment is the strongest predictor of clinical nurses’ intent to remain during disasters.Implications for Nursing and/or Health Policy: To ensure a stable and skilled nursing workforce in disaster situations, it is essential to foster organizational commitment. Strategies should focus on enhancing group cohesion, providing adequate staffing and resources, and supporting organizational commitment among clinical nurses.
Human Pancreatic Cancer Single-Cell Atlas Reveals Association of CXCL10+ Fibroblasts and Basal Subtype Tumor Cells
Authors: Loveless Ian M. , Kemp Samantha B. , Hartway Kailee M. , Mitchell Jacob T. , Wu Yuesong , Zwernik Samuel D. , Salas-Escabillas Daniel James , Brender Sydney , George Madison , Makinwa Yetunde , Stockdale Thais , Gartrelle Kendyll , Reddy Rohit G. , Long Daniel W. , Wombwell Allison , Clark Julie M. , Levin Albert M. , Kwon David , Huang Ling , Francescone Ralph , Vendramini-Costa Débora B. , Stanger Ben Z. , Alessio Adam , Waters Andrew M. , Cui Yuehua , Fertig Elana J. , Kagohara Luciane T. , Theisen Brian , Crawford Howard C. , Steele Nina G. 
Published: January 2025

Abstract

Purpose:
Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard-of-care treatments and have significantly worse overall survival compared with patients with classic subtype–enriched tumors. It is important to develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner.

Experimental Design:
We compiled a single-cell RNA sequencing (scRNA-seq) atlas of the human pancreas with 229 patient samples aggregated from publicly available raw data. We mapped cell type–specific scRNA-seq gene signatures in bulk RNA-seq (n = 744) and spatial transcriptomics (ST; n = 22) and performed validation using multiplex immunostaining.

Results:
Analysis of tumor cells from our scRNA-seq atlas revealed nine distinct populations, two of which aligned with the basal subtype, correlating with worse overall survival in bulk RNA-seq. Deconvolution identified one of the basal populations to be the predominant tumor subtype in nondissociated ST tissues and in vitro tumor cell and patient-derived organoid lines. We discovered a novel enrichment and spatial association of CXCL10+ cancer-associated fibroblasts with basal tumor cells. We identified that besides immune cells, ductal cells also express CXCR3, the receptor for CXCL10, suggesting a relationship between these cell types in the PDAC tumor microenvironment.

Conclusions:
We show that our scRNA-seq atlas (700,000 cells), integrated with ST data, has increased statistical power and is a powerful resource, allowing for expansion of current subtyping paradigms in PDAC. We uncovered a novel signaling niche marked by CXCL10+ cancer-associated fibroblasts and basal tumor cells that could be explored for future targeted therapies.
Exploiting YES1-Driven EGFR Expression Improves the Efficacy of EGFR Inhibitors
Authors: Cuellar-Vite Leslie , Donaubauer Elyse M. , Weber-Bonk Kristen L. , Bobbitt Jessica R. , Ingles Natasha N. , Brzozowski Taylor L. , Abdul-Karim Fadi W. , Booth Christine N. , Keri Ruth A. 
Published: January 2025

Abstract
EGFR is a highly expressed driver of many cancers, yet the utility of EGFR inhibitors (EGFRi) is limited to cancers that harbor sensitizing mutations in the EGFR gene because of dose-limiting toxicities. Rather than conventionally blocking the kinase activity of EGFR, we sought to reduce its transcription as an alternative approach to broaden the therapeutic window for EGFR inhibitors targeting wild-type (WT) or mutant EGFR. We found that YES1 is highly expressed in triple-negative breast cancer (TNBC) and drives cell growth by elevating EGFR levels. Mechanistically, YES1 stimulates EGFR expression by signaling to JNK and stabilizing the AP-1 transcription factor c-Jun. This effect extends beyond TNBC as YES1 also sustains EGFR expression in non–small cell lung cancer cells, including those that harbor the EGFR gatekeeper mutation T790M. The novel ability of YES1 to regulate the expression of WT and mutant EGFR mRNA and protein provides a potential therapeutic opportunity of utilizing YES1 blockade to broadly increase the efficacy of EGFR inhibitors. Indeed, we observed synergy within in vitro and in vivo models of TNBC and non–small cell lung cancer, even in the absence of EGFR-activating mutations. Together, these data provide a rationale for blocking YES1 activity as an approach for improving the efficacy of EGFR-targeting drugs in cancers that have generally been refractory to such inhibitors.
Implications: YES1 sustains EGFR expression, revealing a therapeutic vulnerability for increasing the efficacy of EGFR inhibitors by lowering the threshold for efficacy in tumors driven by the WT or mutant receptor.
PARP Inhibitors Differentially Regulate Immune Responses in Distinct Genetic Backgrounds of High-Grade Serous Tubo-Ovarian Carcinoma
Authors: Doro Pereira Luiza , Wielgos-Bonvallet Monica , Misirlioglu Selim , Khodadai-Jamayran Alireza , Jelinic Petar , Levine Douglas A. 
Published: January 2025

Abstract
Immune checkpoint inhibitors (ICI) have revolutionized treatment for several tumor indications without demonstrated benefit for patients with ovarian cancer. To improve the therapeutic ratio of ICIs in patients with ovarian cancer, several different clinical trials are testing combinations with poly(ADP-ribose) polymerase (PARP) inhibitors. Comparing the immunomodulatory effects of clinically advanced PARP inhibitors (PARPi) may help to identify the best partner to combine with ICIs. We examined the treatment effect of talazoparib (a PARP trapper) and veliparib (a solely PARP enzymatic inhibitor) in homologous recombination deficient (HRD) and homologous recombination proficient high-grade serous tubo-ovarian carcinoma (HGSC) cell lines on immune-related gene expression. We discovered and validated that CXCL8, IL-6, and TNF gene expression were upregulated after talazoparib treatment in both OVCAR3 (HRD) and CAOV3 homologous recombination proficient HGSC cell lines. In contrast, veliparib treatment slightly elevated similar genes exclusively in an HRD HGSC cell line model. We expanded these studies to include olaparib, a PARP trapper less potent than talazoparib, and found effects specific to COV361 (BRCA1 mutant) and OVCAR8 (BRCA1 methylated) HGSC cells but not all HRD HGSC cell lines. Our studies also identified differences among PARP trappers versus veliparib on augmenting CXCL10 expression. Finally, we show that talazoparib modulates the CXCL10 response in cGAS-defective cell lines, independent of the cGAS-STING pathway. These mechanistic studies advance our understanding of how different PARPis affect the immune system in various genetic backgrounds.

Significance:
This work highlights how different PARPis, especially talazoparib, modulate immune-related gene expression in ovarian cancer cells, independent of the cGAS-STING pathway. These findings may improve our understanding of how different PARPis affect the immune system in various genetic backgrounds.
Endothelium Modulates the Prothrombotic Phenotype of Factor V Leiden: Evidence From an Ex Vivo Model
Authors: Schwarz Nadine , Müller Jens , McRae Hannah L. , Reda Sara , Pezeshkpoor Behnaz , Oldenburg Johannes , Pötzsch Bernd , Rühl Heiko 
Published: January 2025

BACKGROUND:
Clinical expressivity of the thrombophilic factor V Leiden (FVL) mutation is highly variable. Recently, we demonstrated an increased APC (activated protein C) response in asymptomatic FVL carriers compared with FVL carriers with a history of venous thromboembolism (VTE) after in vivo coagulation activation. Here, we further explored this association using a recently developed ex vivo model based on patient-specific endothelial colony-forming cells (ECFCs).

METHODS:
ECFCs and citrated plasma were obtained from FVL carriers with previous VTE (VTE+, n=9), FVL carriers without previous VTE (VTE−, n=8), and 7 healthy controls. Coagulation was activated by TF (tissue factor) in defibrinated recalcified plasma added to confluent cell cultures. Thrombin and APC concentration were measured over time, and the respective areas under the curve (AUCs) were calculated. Additionally, inhibition kinetics of exogenously added APC, APC inhibitor levels, and APC sensitivity ratios were measured in plasma. Expression of TM (thrombomodulin) and EPCR (endothelial protein C receptor) on ECFCs was assessed using cell-based ELISAs.

RESULTS:

In autologous plasma on ECFCs, the APC response (AUC APC/AUC thrombin) was higher in FVL VTE− than in FVL VTE+ patients (0.138 versus 0.028;
P
=0.026). APC inhibitor levels, APC inactivation kinetics, and APC sensitivity ratios did not differ between cohorts. Crossover experiments, which combined pooled plasma from FVL VTE− patients with FVL VTE+ ECFCs in the ex vivo model, and vice versa, showed increased APC response rates when FVL VTE− ECFCs were used, regardless of the plasma component. In cell-based ELISAs, TM and EPCR expression showed no significant difference.

CONCLUSIONS:
Although the FVL gene product induces an almost identical APC resistance phenotype in plasma, the endothelial cell–dependent APC response rates differ significantly, with a higher APC response in asymptomatic FVL carriers. Further studies are warranted to elucidate the disease-modulating role of the endothelium in FVL carriers at the molecular level.
Intravascular Imaging as a Performance Measure for Percutaneous Coronary Intervention
Authors: Stein Elliot J. , Mesenbring Elise , Smith Tracy , Hebbe Annika , Salahuddin Taufiq , Waldo Stephen W. , Dyal Michael D. , Doll Jacob A. 
Published: January 2025

BACKGROUND:
Intravascular imaging (IVI) is widely recognized to improve outcomes after percutaneous coronary intervention (PCI). However, IVI is underutilized and is not yet established as a performance measure for quality PCI.

METHODS:
We examined temporal trends of IVI use for all PCIs performed at Veterans Affairs hospitals in the United States from 2010 to 2022 using retrospective observational cohorts. IVI was defined as intravascular ultrasound or optical coherence tomography. A contemporary subset of PCIs from 2020 to 2022 was used to examine clinical characteristics associated with IVI use and test the reliability of IVI as a pass/fail performance measure. We then used a generalized linear mixed model to estimate the proportion of IVI use variability attributable to the hospital, physician, and patient level. Cox proportional hazard models were used to assess the association of IVI with clinical outcomes at 1 year.

RESULTS:
IVI use increased from 12.3% in 2010 to 43.1% in 2022 in 136 071 PCIs included in the study. Among 22 918 PCIs in the contemporary cohort, IVI was more frequent with nonemergent presentations, chronic total occlusions, and left main lesions but usage variability was primarily attributable to hospital (54%) and physician (33%) levels. As a pass/fail performance measure, reliability was high (>0.96) at hospital and physician levels. However, IVI use was not associated with statistically significant differences in mortality or major adverse cardiovascular events in this cohort.

CONCLUSIONS:
IVI use for PCI is increasing rapidly at Veterans Affairs hospitals in the United States but with marked variation at the hospital and physician levels. IVI meets established criteria for an effective performance measure and should be measured and reported by local and national organizations to encourage further uptake. Ongoing training and quality improvement may be required to maximize the benefit of IVI as it is more widely utilized.
Loss of Type 2 Bone Morphogenetic Protein Receptor Activates NOD‐Like Receptor Family Protein 3/Gasdermin E‐Mediated Pyroptosis in Pulmonary Arterial Hypertension
Authors: Tian Xiao‐ting , Peng Zhou‐yang‐fan , Wu Yu‐si , Cao Yuan‐yuan , Li Xue‐chun , Li Ying , Tang Si‐Yuan , Chen Alex F. , Li Xiao‐hui 
Published: January 2025

BACKGROUND
Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency‐mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD‐like receptor family protein 3)/GSDME (gasdermin E)‐mediated pyroptosis pathway.

METHODS AND RESULTS
NLRP3 knockout or short hairpin RNA interference of GSDME was performed in PAH animal models to investigate its effect on PAH progression. In addition, the effects of BMPR2 deficiency and restoration of BMPR2 by BMP9 (bone morphogenetic protein 9) or FK506 on pyroptosis were explored both in animal and cell models. Knockout of NLRP3 or short hairpin RNA interference of GSDME in animal models can alleviate the development of pyroptosis, accompanied with improved endothelial integrity, vascular remodeling, and right ventricular systolic pressure. Blocking BMPR2 is sufficient to induce NLRP3 upregulation and release of inflammatory factor IL‐1β (interleukin‐1β) in pulmonary arterial endothelial cells. Moreover, BMPR2 deficiency can induce GSDME‐mediated pyroptosis through NLRP3 activation in 2 animal models, whereas activation of BMPR2 signaling by FK506 or BMP9 can reverse these phenotypes.

CONCLUSIONS
These findings provide evidence that loss of BMPR2 signaling promotes endothelial cell pyroptosis by enhancing NLRP3/GSDME signaling in PAH. Our findings may provide new insights to explore the inflammatory mechanism of PAH treatment.
Association Between Cardiometabolic Comorbidity Burden and Outcomes in Heart Failure
Authors: Hamo Carine E. , Li Xiyue , Ndumele Chiadi E. , Mukhopadhyay Amrita , Adhikari Samrachana , Blecker Saul 
Published: January 2025

Background
Cardiometabolic comorbidities such as obesity, diabetes, and hypertension are highly prevalent in heart failure (HF). We aimed to examine the association between severity of cardiometabolic comorbidities and hospitalization in patients with HF.

Methods

In a retrospective electronic health record‐based cohort of adults

≥

$$ \ge $$

18 with HF, we categorized individuals based on the number of severe cardiometabolic comorbidities, including hypertension, diabetes, and obesity. Severely uncontrolled comorbidities were defined as systolic blood pressure ≥160 mm Hg, hemoglobin A1c ≥8%, and body mass index ≥35 kg/m
2
. Cox regression models were used to assess the association between cardiometabolic comorbidity burden and time to all‐cause and HF hospitalization at 1 year, adjusting for age, sex, race or ethnicity, and insurance status, smoking, prior hospitalization, and Elixhauser comorbidity index. Stratified analyses were conducted for HF with preserved and reduced ejection fraction.

Results

A total of 26 800 individuals with HF (mean age 75

±

$$ \pm $$

13.7, 46% women, 69% White) experienced 4284 (16%) hospitalizations over a 1‐year period. Compared with individuals with absent comorbidities, those with 1 or 2 to 3 severely uncontrolled comorbidities had a significantly higher risk of all‐cause hospitalization (hazard ratio [HR], 1.23 [95% CI, 1.09–1.39] and HR, 1.57 [95% CI, 1.35–1.83], respectively). We found similar associations for HF hospitalization. These associations were similar among individuals with HF with preserved ejection fraction compared with HF with reduced ejection fraction.

Conclusions
Greater cardiometabolic comorbidity burden was associated with increased risk of all‐cause hospitalization in HF. This reinforces the role for targeting severely uncontrolled cardiometabolic comorbidities to reduce morbidity in HF.