bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Lipotoxicity‐Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis
Authors: Nie Han , Yang Huan , Cheng Lidan , Yu Jianxin 
Published: May 2024

Objective: This study is aimed at investigating diagnostic biomarkers associated with lipotoxicity and the molecular mechanisms underlying diabetic nephropathy (DN).Methods: The GSE96804 dataset from the Gene Expression Omnibus (GEO) database was utilized to identify differentially expressed genes (DEGs) in DN patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the DEGs. A protein–protein interaction (PPI) network was established to identify key genes linked to lipotoxicity in DN. Immune infiltration analysis was employed to identify immune cells with differential expression in DN and to assess the correlation between these immune cells and lipotoxicity‐related hub genes. The findings were validated using the external dataset GSE104954. ROC analysis was performed to assess the diagnostic performance of the hub genes. The Gene set enrichment analysis (GSEA) enrichment method was utilized to analyze the key genes associated with lipotoxicity as mentioned above.Result: In this study, a total of 544 DEGs were identified. Among them, extracellular matrix (ECM), fatty acid metabolism, AGE‐RAGE, and PI3K‐Akt signaling pathways were significantly enriched. Combining the PPI network and lipotoxicity‐related genes (LRGS), LUM and ALB were identified as lipotoxicity‐related diagnostic biomarkers for DN. ROC analysis showed that the AUC values for LUM and ALB were 0.882 and 0.885, respectively. The AUC values for LUM and ALB validated in external datasets were 0.98 and 0.82, respectively. Immune infiltration analysis revealed significant changes in various immune cells during disease progression. Macrophages M2, mast cells activated, and neutrophils were significantly associated with all lipotoxicity‐related hub genes. These key genes were enriched in fatty acid metabolism and extracellular matrix‐related pathways.Conclusion: The identified lipotoxicity‐related hub genes provide a deeper understanding of the development mechanisms of DN, potentially offering new theoretical foundations for the development of diagnostic biomarkers and therapeutic targets related to lipotoxicity in DN.
MYC Family Amplification Dictates Sensitivity to BET Bromodomain Protein Inhibitor Mivebresib (ABBV075) in Small-Cell Lung Cancer
Authors: Plotnik Joshua P. , Zha Zheng , Feng Weiguo , Lee Irene , Riehm Jacob , McClure Ryan A. , Sandoval Stephanie , Uziel Tamar , Murphy Erin , Lu Xin , Lam Lloyd T. 
Published: May 2024

Abstract
Small-cell lung cancer (SCLC) accounts for nearly 15% of all lung cancers. Although patients respond to first-line therapy readily, rapid relapse is inevitable, with few treatment options in the second-line setting. Here, we describe SCLC cell lines harboring amplification of MYC and MYCN but not MYCL1 or non-amplified MYC cell lines exhibit superior sensitivity to treatment with the pan-BET bromodomain protein inhibitor mivebresib (ABBV075). Silencing MYC and MYCN partially rescued SCLC cell lines harboring these respective amplifications from the antiproliferative effects of mivebresib. Further characterization of genome-wide binding of MYC, MYCN, and MYCL1 uncovered unique enhancer and epigenetic preferences.
Implications: Our study suggests that chromatin landscapes can establish cell states with unique gene expression programs, conveying sensitivity to epigenetic inhibitors such as mivebresib.
Single-Cell Dissection of the Immune Response After Acute Myocardial Infarction
Authors: van Blokland Irene V. , Oelen Roy , Groot Hilde E. , Benjamins Jan Walter , Pekayvaz Kami , Losert Corinna , Knottenberg Viktoria , Heinig Matthias , Nicolai Leo , Stark Konstantin , van der Harst Pim , Franke Lude , van der Wijst Monique G.P. 
Published: May 2024

BACKGROUND:
The immune system’s role in ST-segment–elevated myocardial infarction (STEMI) remains poorly characterized but is an important driver of recurrent cardiovascular events. While anti-inflammatory drugs show promise in reducing recurrence risk, their broad immune system impairment may induce severe side effects. To overcome these challenges, a nuanced understanding of the immune response to STEMI is needed.

METHODS:
For this, we compared peripheral blood mononuclear single-cell RNA-sequencing (scRNA-seq) and plasma protein expression over time (hospital admission, 24 hours, and 6–8 weeks post-STEMI) in 38 patients and 38 controls (95 995 diseased and 33 878 control peripheral blood mononuclear cells).

RESULTS:

Compared with controls, classical monocytes were increased and CD56
dim
natural killer cells were decreased in patients with STEMI at admission and persisted until 24 hours post-STEMI. The largest gene expression changes were observed in monocytes, associating with changes in toll-like receptor, interferon, and interleukin signaling activity. Finally, a targeted cardiovascular biomarker panel revealed expression changes in 33/92 plasma proteins post-STEMI. Interestingly, interleukin-6R, MMP9 (matrix metalloproteinase-9), and LDLR (low-density lipoprotein receptor) were affected by coronary artery disease–associated genetic risk variation, disease status, and time post-STEMI, indicating the importance of considering these aspects when defining potential future therapies.

CONCLUSIONS:
Our analyses revealed the immunologic pathways disturbed by STEMI, specifying affected cell types and disease stages. Additionally, we provide insights into patients expected to benefit most from anti-inflammatory treatments by identifying the genetic variants and disease stage at which these variants affect the outcome of these (drug-targeted) pathways. These findings advance our knowledge of the immune response post-STEMI and provide guidance for future therapeutic studies.
The Effects of Housing Price Declines on Children's Educational Outcomes
Authors: Been Vicki , Ellen Ingrid , Figlio David , Nelson Ashlyn Aiko , Ross Stephen L. , Schwartz Amy Ellen , Stiefel Leanna 
Published: May 2024

Abstract
We examine the effects that household exposure to housing price declines, captured by measures of negative equity, have on children's academic performance, using data on public school students and housing transactions from the State of Florida. Our empirical strategy exploits variation over time in the timing of family moves to account for household sorting into neighborhoods and schools and selection into initial mortgage terms. In contrast to the existing literature on the effects of foreclosure, we find that students with the highest risk of negative equity exhibit significantly higher test score growth, with the largest effects among Black students and students qualifying for free or reduced-priced lunch. We find evidence supporting two underlying mechanisms: (1) families in negative equity may reduce the impact of income losses on consumption by forgoing mortgage payments, and (2) families exposed to high levels of negative equity may move to schools that received higher average school report card grades. While negative equity and foreclosure are undesirable, negative equity may have encouraged homeowners to forgo mortgage payments to mitigate the impact of the Great Recession, and temporarily reduced the housing market barriers low-income households faced in accessing educational opportunities.
Assessing School District Decision Making: In-Person Schooling and COVID-19 Transmission
Authors: Christian Alvin , Jacob Brian , Singleton John D. 
Published: May 2024

Abstract
Recent controversies have highlighted the importance of local school district governance, but little empirical evidence exists evaluating the quality of district policy makers or policies. In this paper, we take a novel approach to assessing school district decision making. We posit a model of rational decision making under uncertainty that emphasizes districts learning over time. We test the predictions from the model using data on a set of highly visible and consequential decisions facing school district leaders—the choice of learning mode during the 2020–21 school year. We find that district behavior is consistent with a Bayesian learning process in several key respects. Districts respond on the margin to health risks: All else equal, a marginal increase in new cases reduces the probability that a district offers in-person instruction the next week. This negative response is magnified when the district was in-person the prior week and attenuates in magnitude over the school year, suggesting that districts learn from experience about the effect of in-person learning on disease transmission in schools. We also find evidence that districts are influenced by the learning mode decisions of peer districts, but not their peers' experiences with in-person instruction and disease transmission, which implies that some important frictions exist.
The Impact of Theology on Disaffiliation, Disengagement, and Disbelief
Authors: Raymond Christopher D. 
Published: May 2024

Abstract
While the reasons for the differences in the growth rates of conservative and liberal churches are well studied, one important potential reason for this difference has received little attention. The argument that liberal theology undermines the basis of belief implies that those with liberal theological views may be more likely to lose faith and disaffiliate than those holding conservative theologies that reinforce adherents’ religious faith and practice. Using a nationally representative panel survey of the American public, the analysis performed here shows that those with liberal theologies were significantly more likely to disaffiliate from Christianity, attend church less often, and cease believing in God between the two waves of the survey than those with more conservative theologies. On the basis of these findings, more attention should be given to the role that theology may play in understanding patterns of secularization.
‘They Will Shoot You to a Pulp!’ The Racialisation of Migrant Workers in the Emotive Cyberspace of ptt
Authors: Cockel Isabelle 
Published: May 2024

Abstract
This article analyses how social media users ‘reimagined’ the death of an undocumented Vietnamese migrant worker in 2017 in Taiwan and revealed their views on ethnic hierarchy and the judicial system as a public institution. By conceptualising posting on ptt, a Chinese-language bbs platform likened to Reddit, as a racialising process, this article finds posters’ reimagination of this event being characterised by criminalisation, dehumanisation, and distrust of the judicial system. Laden with emotions, some users displayed racial othering of migrant workers through militant masculinity, whereas others called for intersubjectivity and respect for life and rights. Some users equated being pro-police with being pro-violence, in contrast to others’ demand to regulate the police’s use of firearms. The totality of these views suggests that ptt is a volatile sociopolitical space facilitating antagonistic views. The racialising discourse echoes the exclusionary guest worker system adopted in Taiwan that regards migrant workers as the disposable and inferior other.
Listening to Stakeholders III: Potential Users Evaluate Product Content and Design for Subseasonal Extreme Precipitation Forecasts
Authors: Schroers Melanie A. , Dickinson Ty A. , Ćwik Paulina , McPherson Renee A. , Martin Elinor R. 
Published: May 2024

Abstract
Extreme precipitation over a 2-week period can cause significant impacts to life and property. Trustworthy and easy-to-understand forecasts of these extreme periods on the subseasonal-to-seasonal time frame may provide additional time for planning. The Prediction of Rainfall Extremes at Subseasonal to Seasonal Periods (PRES2iP) project team conducted three workshops over 6 years to engage with stakeholders to learn what is needed for decision-making for subseasonal precipitation. In this study, experimental subseasonal-to-seasonal (S2S) forecast products were designed, using knowledge gained from previous stakeholder workshops, and shown to decision-makers to evaluate the products for two 14-day extreme precipitation period scenarios. Our stakeholders preferred a combination of products that covered the spatial extent, regional daily values, with associated uncertainty, and text narratives with anticipated impacts for planning within the S2S time frame. When targeting longer extremes, having information regarding timing of expected impacts was seen as crucial for planning. We found that there is increased uncertainty tolerance with stakeholders when using products at longer lead times that typical skill metrics, such as critical success index or anomaly correlation coefficient, do not capture. Therefore, the use of object-oriented verification that allows for more flexibility in spatial uncertainty might be beneficial for evaluating S2S forecasts. These results help to create a foundation for the design, verification, and implementation of future operational forecast products with longer lead times, while also providing an example for future workshops that engage both researchers and decision-makers.
The Impact of Palliative Care Consultation on Aggressive Medical Interventions in End-of-life Among Patients with Metastatic Breast Cancer: Insights from the U.S. National Patient Sample
Authors: Zhang Zidong , Lovell Alexandria , Subramaniam Divya S. , Hinyard Leslie 
Published: May 2024

Background Advancement in treatment has led to prolonged survival and a rising number of women living with metastatic breast cancer (MBC) in the United States. Due to its high symptom burden, it is recommended that palliative care be integrated into the standard care to help improve quality of life. However, little is known about the use of palliative care among MBC patients in the nation. Objectives To determine utilization of palliative care consult (PCC) after metastasis and the influence of PCC on healthcare utilization in the end of life among women living with MBC in the US. Methods This retrospective cohort study examined a national electronic health record database to quantify the PCC use after metastasis diagnosis until death and the associations of PCC with Emergency Department (ED), Intensive Care Unit (ICU), and chemotherapies in the end-of-life women (age ≥ 18 years) living with MBC. Results From a cohort of 2615 deceased MBC patients, 37% received PCC in the last 6 months of life. Patients who had received PCC in the end-of-life were more likely to be hospitalized, admitted to ED and ICU, and receive chemotherapies in the last 60 days before death. However, patients who had received end-of-life PCC had less hospital and ED visits and received less chemotherapies after PCC initiated. Conclusion While PCC can reduce end-of-life aggressive interventions, it was underutilized among patients with MBC in the end-of-life. A myriad of clinical and patient factors may still challenge timely consultation. We urge for future endeavors in developing strategies to remove barriers in the implementation, especially earlier in the disease course, to assure timely PC treatments and reduce discomfort amid aggressive interventions for MBC.
The Contribution of Psychological Symptoms to Cognitive Difficulties in Youth With Postural Orthostatic Tachycardia Syndrome and Chronic Pain
Authors: Tsai Owens Michele , Fischer Philip R. , Sim Leslie , Kirsch Alexandra , Homan Kendra , Zaccariello Michael , Sawchuk Nicholas , LeMahieu Allison , Geske Jennifer , Harbeck-Weber Cynthia 
Published: May 2024

Introduction Subjectively experienced cognitive difficulties are common in youth with postural orthostatic tachycardia syndrome. The pathophysiological and psychological contributions of these cognitive impairments remain unclear. Method Participants were 96 adolescents and young adults diagnosed with postural orthostatic tachycardia syndrome and admitted to an intensive pain treatment program. Participants completed cognitive assessment and measures of postural orthostatic tachycardia syndrome symptoms, pain intensity, pain catastrophizing, anxiety, depression, and functional disability. Results Self-reported autonomic symptom intensity, but not severity of heart rate change, was associated with cognitive performance. Symptoms of depression were associated with decreases in most measures of cognitive functioning. Pain intensity, pain catastrophizing, and depression but not cognitive scores and physiological measures, were significant predictors of disability. Conclusion Depression appears to be a significant contributor to the cognitive difficulties in youth with postural orthostatic tachycardia syndrome. These findings highlight the importance of assessing and treating affective symptoms in this population along with medical and lifestyle approaches to treating postural orthostatic tachycardia syndrome symptoms.
Ferritin Levels on Hospital Admission Predict Hypoxic-Ischemic Encephalopathy in Patients After Out-of-Hospital Cardiac Arrest: A Prospective Observational Single-Center Study
Authors: Nickelsen Swantje , Grosse Darrelmann Eleonore , Seidlmayer Lea , Fink Katrin , Britsch Simone , Duerschmied Daniel , Scharf Ruediger E. , Elsaesser Albrecht , Helbing Thomas 
Published: May 2024

Aim Out-of-hospital cardiac arrest (OHCA) is a major health concern in Western societies. Poor outcome after OHCA is determined by the extent of hypoxic-ischemic encephalopathy (HIE). Dysregulation of iron metabolism has prognostic relevance in patients with ischemic stroke and sepsis. The aim of this study was to determine whether serum iron parameters help to estimate outcomes after OHCA. Methods In this prospective single-center study, 70 adult OHCA patients were analyzed. Serum ferritin, iron, transferrin (TRF), and TRF saturation (TRFS) were measured in blood samples drawn on day 0 (admission), day 2, day 4, and 6 months after the return of spontaneous circulation (ROSC). The association of 4 iron parameters with in-hospital mortality, neurological outcome (cerebral performance category [CPC]), and HIE was investigated by receiver operating characteristics and multivariate regression analyses. Results OHCA subjects displayed significantly increased serum ferritin levels on day 0 and lowered iron, TRF, and TRFS on days 2 and 4 after ROSC, as compared to concentrations measured at a 6-month follow-up. Iron parameters were not associated with in-hospital mortality or neurological outcomes according to the CPC. Ferritin on admission was an independent predictor of features of HIE on cranial computed tomography and death due to HIE. Conclusion OHCA is associated with alterations in iron metabolism that persist for several days after ROSC. Ferritin on admission can help to predict HIE.
A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy
Authors: Guan Qingxia , Liu Yumeng , Xia Zhaorui , Zhang Yue , Wang Liping , Wang Yanhong , Zou Shujun , Lv Shaowa , Zhou Xiaoying 
Published: May 2024

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3’-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.
Low-Income Participants’ Preference Between Financial Incentives for Behavioral Goals vs Weight Loss Targets and Associations With Behavioral Goal Adherence
Authors: Adhiyaman Akshitha , Jay Melanie , Chung Un Young Rebecca , Gronda Andres N. , Tseng Chi-Hong , Wylie-Rosett Judith , Wittleder Sandra , Wali Soma , Ladapo Joseph A. , Orstad Stephanie L. 
Published: May 2024

Purpose Examine associations between whether participants’ were matched to their preferred financial incentive design and behavioral goal adherence in a weight management intervention. Design Secondary quantitative analysis incorporating qualitative survey data. Setting Primary care clinics in socioeconomically disadvantaged communities in New York City and Los Angeles. Subjects 668 participants (mean age 47.7 years, 81.0% female, 72.6% Hispanic) with obesity were enrolled in the Financial Incentives foR Weight Reduction (FIReWoRk) intervention. Measures We explored qualitatively participant’s reasons for hypothetically choosing a behavioral goal-directed vs a weight loss outcome-based financial incentive program. Additionally, behavioral adherence to different goals was collected at the 6-month timepoint, categorized by match to preferred financial incentive design. Analysis Logistic regression was used to examine if participants with certain demographic and higher psychosocial factors were more likely to choose goal-directed over outcome-based incentives. Additionally, logistic regression was used to test for associations between preference and behavioral adherence, using incentive type as an interaction term. Results 60.2% of participants preferred the goal-directed incentive, with the majority stating that it was more structured. Married participants were more likely to prefer goal-directed incentives (OR = 1.57, CI = 1.06-2.33, P = .025). Moderation analysis revealed that participants who preferred goal-directed and were matched to goal-directed had greater rates of behavioral adherence for program attendance and self-weighing, but not dietary tracking and physical activity tracking, compared to those who preferred outcome-based and were matched to outcome-based. Conclusion Receiving one’s preferred incentive design may not play a strong role in behavioral goal adherence during financially incentivized weight loss interventions.