bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Network Pharmacology and Transcriptome Sequencing to Investigate the Mechanism of Action of Luteolin and Quercetin in Treating Obesity
Authors: Liu Ruoshuang , Wang Zhaoxiang , Shi Kangru , Shen Yirong , Yu Xiawen , Cheng Caiqin , Xia Yue , Dai Guoyu , Zhao Zhicong , Xiong Yuyun , Wang Dong , Yang Ling , Yuan Guoyue , Jia Jue 
Published: February 2025

ABSTRACTLuteolin and quercetin, which are flavonoids, are present in various traditional Chinese medicines. Although they have been shown to improve obesity, the specific mechanisms of action remain unclear. This study aimed to determine pivotal targets and major regulatory pathways involved in their mechanisms of action using network pharmacology and transcriptome sequencing. Data on luteolin/quercetin‐related targets were acquired from the PharmMapper platform, and data on known obesity‐related targets were collected from the OMIM and GeneCards databases. Differentially expressed genes (DEGs) involved in luteolin and quercetin action that regulate adipogenic differentiation were identified using RNA sequencing (RNA‐seq). Bioinformatic analyses were performed to identify potential target genes and pathways regulated by luteolin/quercetin during adipogenesis. Finally, key genes and pathways were validated through quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting. Network pharmacology showed that luteolin/quercetin was closely associated with anti‐obesity targets. The related pathways were metabolic, PI3K/AKT, and MAPK pathways. RNA‐seq revealed 91 common DEGs involved in luteolin/quercetin regulation of adipogenic differentiation. Finally, nine potential target genes (including CIDEC, Mgll, Slc2a4, Pck1, and PNPLA3) were identified, and the AMPK and AKT signaling pathways were verified. The present study provides novel information regarding the molecular mechanism of luteolin and quercetin action in treating obesity and demonstrates their therapeutic effects through multiple targets and pathways.
Electrophysiological Alterations in the Progression of Parkinson's Disease and the Therapeutic Effect of Tetrabenazine on Rats With Levodopa‐Induced Dyskinesia
Authors: Bi Yuewei , Wang Pengfei , Li Min , Wang Zhuyong , Lv Siyuan , Yang Yong , Zhang Wangming 
Published: February 2025

ABSTRACTAimsDopamine replacement therapy is the backbone of Parkinson's disease (PD) treatment. However, long‐term levodopa (L‐DOPA) administration can lead to the severely disabling motor complication L‐DOPA‐induced dyskinesia (LID), for which standard, effective therapy is currently lacking. This study was conducted to characterize the distinct neural electrophysiological patterns involved in the progression of PD and to examine the efficacy of tetrabenazine, a vesicular monoamine transporter‐2 inhibitor, in alleviating dyskinesia and its underlying electrophysiological mechanism.MethodsElectrophysiological analysis was performed to obtain power spectrum density and functional connectivity information from local field potential (LFP) data recorded from the primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states in PD model rats. Behavioral tests and abnormal involuntary movements (AIMs) scoring were conducted to confirm PD model establishment and assess LID severity.ResultsIncreased beta oscillations and abnormally strengthened beta causality in the M1 → DLS direction and exaggerated beta‐band M1–DLS functional connectivity were observed in the PD state. L‐DOPA administration suppressed beta activity and augmented gamma power in the M1 and DLS, with increased gamma causality in the M1 → DLS direction and beta causality in the DLS → M1 direction, as well as elevated gamma‐band M1–DLS functional connectivity. Tetrabenazine strongly ameliorated dyskinetic manifestations. It suppressed gamma power in the M1 and DLS, reduced gamma causality and increased beta causality in the M1 → DLS direction, reduced beta causality in the DLS → M1 direction, and reduced gamma‐band M1–DLS functional connectivity.ConclusionTetrabenazine abrogated aberrant gamma activity to improve LID symptoms, which provides compelling evidence for its future clinical application in LID therapy.
Lung Transplant in Patients With Human Immunodeficiency Virus: A Case Series
Authors: Ganguly Paulamy , Varadarajan Ramya , Adelman Max W. , Arunachalam Priya , Yau Simon , Youssef Jihad G. , Goodarzi Ahmad 
Published: February 2025

ABSTRACTBackgroundHistorically, patients with human immunodeficiency virus (PWH) were at higher risk for pulmonary morbidities than patients without HIV. Lung transplantation in PWH has been limited by uncertain outcomes and a lack of guidelines for transplantation and immunosuppression. However, several case reports in the United States and Europe have demonstrated that lung transplantation in PWH is feasible. Although there remain concerns regarding these patients as higher‐risk recipients, lung transplantation is feasible with careful modification of immunosuppression and close monitoring.MethodsWe performed lung transplantation on three PWHs and analyzed their post‐transplant outcomes to determine the feasibility of lung transplant in PWH.ResultsWe found that all three patients (mean age 59, SD 10.98) with HIV underwent lung transplantation. Two of the three patients experienced acute cellular rejection that resolved with intravenous corticosteroids. None had long‐term complications including chronic rejection, antibody‐mediated rejection, or infections. All three patients maintained baseline HIV therapy following transplantation with adequate HIV disease control.ConclusionAlthough PWH has an increased risk of pulmonary comorbidities compared to the general population, lung transplantation appears to be a feasible treatment option supported by the growing body of literature and the three cases described here.
Safety and Tolerability of SGLT‐2 Inhibitors Following Lung Transplantation
Authors: Wilcox Peter , Walter Krysta , Troost Jonathan , Belloli Elizabeth 
Published: February 2025

ABSTRACTSodium‐glucose cotransporter‐2 inhibitors (SGLT2i's) are frequently prescribed for T2DM control, with additional efficacy in congestive heart failure therapy and preserving renal function in CKD. Despite their potential to mitigate comorbidities, prescribing of SGLT2i's following solid organ transplantation has been limited due to safety concerns regarding infection, renal function, and diabetic ketoacidosis. SGLT2i prescription following transplantation of other solid organs has been evaluated, but only one study included a limited number of lung transplant recipients. We performed a retrospective case control study of all patients in Michigan Medicine clinics with a prior lung transplant who were prescribed an SGLT2i between January, 2010 and March, 2023. We collected demographic information, medical history pertaining to transplant, SGLT2i prescription history, and abstracted safety, tolerability, and efficacy outcomes for comparison between the SGLT2i cohort and a control population. Among 20 patients who met inclusion criteria, median SGLT2i prescription duration was 372 days. There were no UTI's or GU infections, and severe AKI occurred in five patients. There was a median reduction of 0.6% in hemoglobin A1c within the SGLT2i group not observed in controls (p = 0.09). Our findings demonstrate safety and tolerability of SGLT2i's following lung transplantation and suggest efficacy in controlling T2DM or PTDM.
Associations of Mid‐ and Late‐Life Fasting Blood Glucose Levels With Dementia Risk Among Patients With Diabetes: Framingham Heart Study
Authors: Li Jinlei , Liu Chunyu , Ang Ting Fang Alvin , Au Rhoda 
Published: February 2025

ABSTRACTBackgroundDiabetes is an established risk factor for dementia. However, the association has been less consistent at the population level and may vary over the lifespan. The impacts may be influenced by glucose fluctuation over lifetime.MethodsWe used data from the Framingham Offspring cohort to evaluate the dementia risk associated with fasting blood glucose (FBG) across age ranges. Cox proportional hazards regression models were fitted to investigate the association of diabetes status at each examination with dementia risk, and the associations between FBG levels and dementia across age spans. Group‐based trajectory models were used to create FBG trajectories from mid to late‐life for comparison.ResultsHigher FBG level at midlife was not associated with an increased risk of dementia. For participants with diabetes, higher FBG at age 60 and 70 years was associated with subsequent dementia (HR: 1.72, 95% CI: 1.07–2.75; HR: 1.91, 95% CI: 1.24–2.91). Diabetic participants with first midlife increasing and then late‐life declining patterns of FBG were at greater increased risk of dementia compared to participant without diabetes. (HR: 2.00, 95% CI: 1.04–3.85).ConclusionThe relationship between FBG and dementia risk was heterogeneous across the adult age range. Diabetes at midlife is a risk factor for dementia, but high glucose levels at 60–70 years followed by a decline suggests that less controlled diabetes during high age risk for dementia onset may represent another prodromal risk factor and presymptomatic metabolic indicator of dementia.
The role of electroencephalography in epilepsy research—From seizures to interictal activity and comorbidities
Authors: Lisgaras Christos Panagiotis , de la Prida Liset M. , Bertram Edward , Cunningham Mark , Henshall David , Liu Anli A. , Gnatkovsky Vadym , Balestrini Simona , de Curtis Marco , Galanopoulou Aristea S. , Jacobs Julia , Jefferys John G. R. , Mantegazza Massimo , Reschke Cristina R. , Jiruska Premysl 
Published: February 2025

AbstractElectroencephalography (EEG) has been instrumental in epilepsy research for the past century, both for basic and translational studies. Its contributions have advanced our understanding of epilepsy, shedding light on the pathophysiology and functional organization of epileptic networks, and the mechanisms underlying seizures. Here we re‐examine the historical significance, ongoing relevance, and future trajectories of EEG in epilepsy research. We describe traditional approaches to record brain electrical activity and discuss novel cutting‐edge, large‐scale techniques using micro‐electrode arrays. Contemporary EEG studies explore brain potentials beyond the traditional Berger frequencies to uncover underexplored mechanisms operating at ultra‐slow and high frequencies, which have proven valuable in understanding the principles of ictogenesis, epileptogenesis, and endogenous epileptogenicity. Integrating EEG with modern techniques such as optogenetics, chemogenetics, and imaging provides a more comprehensive understanding of epilepsy. EEG has become an integral element in a powerful suite of tools for capturing epileptic network dynamics across various temporal and spatial scales, ranging from rapid pathological synchronization to the long‐term processes of epileptogenesis or seizure cycles. Advancements in EEG recording techniques parallel the application of sophisticated mathematical analyses and algorithms, significantly augmenting the information yield of EEG recordings. Beyond seizures and interictal activity, EEG has been instrumental in elucidating the mechanisms underlying epilepsy‐related cognitive deficits and other comorbidities. Although EEG remains a cornerstone in epilepsy research, persistent challenges such as limited spatial resolution, artifacts, and the difficulty of long‐term recording highlight the ongoing need for refinement. Despite these challenges, EEG continues to be a fundamental research tool, playing a central role in unraveling disease mechanisms and drug discovery.
Ceramides and Skin Health: New Insights
Authors: Yong Tze Lek , Zaman Rahela , Rehman Navedur , Tan Chung Keat 
Published: February 2025

ABSTRACTCeramide has transitioned from an incidental discovery to a vital element in skincare, becoming a thoroughly studied compound in the quest to treat skin conditions. Creating a moisture barrier, preserving hydration, regulating pH, controlling inflammation, and enhancing skin functions and appearance are among its established benefits. It is often used medically to repair skin barrier defects, as observed in inflammatory skin conditions like atopic dermatitis (AD) and dry skin types. Furthermore, ceramide and its metabolites are commonly used as predictors before disease manifestation and for prognostication processes, thus can be used as biomarker for clinical diagnosis as well. In the last couple of decades, momentum was also seen in the pre‐clinical studies involving anti‐cancer and nanotechnology field, whereby ceramide was also used as a drug, a carrier, or even adjunct formulation to increase efficacy of treatment such as chemotherapy. Approaches to increase ceramide levels include directly replenishing lost ceramides with natural extracts, synthetic pseudo‐ceramides, or ceramide‐like analogues, as well as using supplements that stimulate the body's natural ceramide production. Although ceramide is a well‐known treatment in skincare and for common skin conditions like AD and psoriasis, its development and related pharmacology for severe skin conditions, such as skin cancer, remain in pre‐clinical stages. Hence, the purpose of this research is to explore the role of ceramide in skin health and its application in common skin diseases.
Changes in Relationship Skills and Parenting Stress Among Vulnerable Couples Participating in Couple Relationship Education Before Versus During the COVID‐19 Pandemic
Authors: Campbell Avery R. , Futris Ted G. , Richardson Evin W. , Gilbert Abigail Scott 
Published: February 2025

ABSTRACTThe COVID‐19 pandemic marked sudden changes for many parenting couples that heightened levels of parenting stress. A strong couple relationship can serve as a protective buffer against parenting stress, especially during acute stress resulting from the COVID‐19 pandemic. Couple relationship education (CRE) teaches couple relationship skills (CRS) that can promote positive couple functioning and, in turn, lower levels of parenting stress. Guided by the Vulnerability‐Stress‐Adaptation model and the spillover hypothesis, multigroup latent growth curve modeling (LGCM) was used to compare trajectories of change in CRS and parenting stress for 859 parents receiving child welfare services who attended CRE programming prior to the COVID‐19 pandemic versus 144 parents who attended CRE during the COVID‐19 pandemic. Although both samples reported significant positive change in CRS, only the pre‐COVID sample showed significant declines in parenting stress over time. Additionally, findings showed a significant association between increases in CRS and a decrease in parenting stress in the pre‐COVID sample only. These findings suggest that couples who attend CRE may experience benefits in their couple relationship that spillover to their roles as parents. However, the association between positive changes in CRS and decreases in parenting stress may not be as strong when parents are experiencing an acute stressor (i.e., pandemic‐related stressors).
Real‐world interpatient variability in the pharmacokinetics of levetiracetam
Authors: Chykharivska Alina , Kagan Leonid , Wagner Mary , Brunetti Luigi 
Published: February 2025

AbstractBackgroundLevetiracetam (LEV) is an antiepileptic drug (AED) used to treat a variety of seizures in adult and pediatric populations. It is an ideal AED due to its favorable pharmacokinetic (PK) and pharmacodynamic profile and lack of interactions with other AEDs.MethodsThis retrospective cohort study was designed to identify covariates that affect LEV clearance and volume of distribution and to generate a population PK model. Adults with a seizure history receiving LEV during hospital admission with a minimum of one serum LEV concentration available were included in the study. Population PK modeling and covariate testing was performed with MONOLIX Suite 2020R1 (Lixoft, France).ResultsA total of 162 serum concentrations were collected from 143 patients. Age, sex, body weight descriptors, serum creatinine, creatinine clearance (CrCL), serum albumin, liver enzymes, and total bilirubin were evaluated. Body surface area (BSA) was a significant covariate for the apparent volume of distribution (V/F). The exclusion of BSA as a covariate of V/F increased the objective function value (OFV) 5.6. CrCL was a significant covariate of apparent plasma clearance (CL/F). The exclusion of CrCL increased the OFV by 18.16 and significantly increased the root square error (RSE) % of the between‐subject variabilities of the parameters.ConclusionLEV clearance is an effective predictor of serum concentration. CrCL was a significant covariate influencing LEV clearance, and BSA was found to influence the volume of distribution. Further studies are needed to determine the effect of body weight descriptors on LEV clearance and, ultimately, outcomes.
“Don't Work for Soyciety:” Involuntary Celibacy and Unemployment
Authors: Beckett‐Herbert AnnaRose , Shor Eran 
Published: February 2025

ABSTRACTSurveys of involuntary celibates (“incels”) suggest that they tend to be not in education, employment or training (NEET) at disproportionately high rates. However, it remains unclear whether and how being NEET is connected to incels' ideology and life circumstances. To investigate this, we conducted a qualitative thematic analysis of over a thousand comments posted on the main incel forum, incels.is. We found that many users promoted unemployment and social disengagement as a form of retaliation against a society they feel has harmed them. These users often encouraged other incels to embrace a life of isolation and used employment status as an assessment of commitment to the incel identity. Users also reported experiences of discrimination, bullying, and feeling incompetent at workplaces and educational institutions. We conclude that, for incels, being unemployed can be both an ideological stance and a consequence of their experienced or perceived marginalization.
HISTORICAL ANTIFASCISM AND THE GLOBAL LEFT
Authors: RENAUD TERENCE 
Published: February 2025

ABSTRACTJoseph Fronczak's Everything Is Possible: Antifascism and the Left in the Age of Fascism presents antifascism in the 1920s and 1930s as a universal cause that united people across social and ideological divides, creating the discursive framework for the global Left we know today. It revises standard accounts according to which the Left originated either with the Atlantic revolutions circa 1800 or with the international workers’ movement that took shape in the late nineteenth century. This article accepts the weak form of the book's argument that the antifascist era was remarkably creative and essential for understanding the development of today's Left. However, it rejects the strong form of the argument that dissociates the Left from any prior history in the revolutionary tradition or the workers’ movement. To complement the book's discursive analysis of languages of the Left, this article outlines a structural analysis of antisystemic opposition in the contexts of global capitalism, imperialism, and mass politics. What results is a long‐term concept of the Left that, among other things, highlights the promise and pitfalls of antifascist populism. The core problem of defining the Left is accounting for the historical disjuncture between unity of antisystemic consciousness and unity of organized action.
ALDOB suppresses the activity of CD8+ T cells in colorectal cancer via the WNT signaling pathway
Authors: Liu Jinwei , Hu Chao , Jin Yuan 
Published: February 2025

AbstractThe glycolytic enzyme, fructose‐1,6‐bisphosphate aldolase B (ALDOB), is recognized for its key role in shaping tthe umor immune microenvironment. However, the precise ways in which it influences the CD8+ T cell immune response in colorectal cancer (CRC) are still largely unknown. This study is designed to elucidate the interplay between ALDOB and the immune system in CRC. We analyzed the high expression of ALDOB in CRC tissues and cells through bioinformatics, clinical samples and in vitro experiments, finding that it promoted tumor progression. Its high expression was negatively correlated with CD8 expression and positively correlated with PDL1 expression. Further cell experiments revealed that ALDOB overexpression enhanced the expression of WNT signaling pathway‐related proteins (β‐catenin and c‐myc), which in turn promoted PDL1 expression in CRC cells, inhibiting the proliferation and killing effect of CD8+ T cells in co‐culture systems. Our findings disclose how ALDOB influences CD8+ T cell recruitment and antitumor immune function, proposing it as a potential target for the treatment of CRC.
Impact of violence on work morale on Taiwanese nurses: The moderator of perceived organizational support
Authors: Chen Kuan‐Yang , Wu Hsuan‐Man , Wu Hsiu‐Chuan 
Published: February 2025

AbstractAimThis study aimed to investigate the impact of workplace violence on work morale, of nurses specifically focusing on work satisfaction and work commitment, and whether perceived organizational support moderates this relationship.BackgroundPrior research on this topic has predominantly explored the effects of workplace violence on the emotional antecedents of nurses’ turnover intentions, with limited attention given to organizational factors. The literature and evidence on this subject are inconsistent and often contradictory. Moreover, studies that address contingency factors within the dynamics of this relationship are lacking.MethodsA sample of 550 nurses at a medical center in Taiwan provided the initial data collection pool, from which 300 respondents were selected for further analysis. To evaluate the proposed hypotheses, partial least squares structural equation modeling was applied.FindingsWhen considered in the context of affective events theory and social support theory, the findings confirm workplace violence has significant effects on both work satisfaction and work commitment. Additionally, perceived organizational support acted as a moderating factor in this relationship.ConclusionThis study aligns with the Sustainable Development Goals established by the United Nations, particularly those concerning addressing gender equality (key themes addressed by goal 5: workplace violence and harassment) to foster a supportive work environment for women. This research contributes to the literature by elucidating the specific moderating mechanisms through which perceived organizational support influences the relationship between workplace violence and work morale.Implications for nursing and nursing policyThe results of this study have a significant impact on international nursing policies focused on enhancing the safety and involvement of female nurses in the workplace, especially regarding workplace violence issues. Hospital administrators should create a positive nursing work environment that maintains nurses’ morale and reduces the negative effects of workplace violence. Additionally, organizations should provide nurses with supportive resources or establish policies to enhance nurses’ work morale.