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White Supremacist Beliefs Predict Discrimination but Not Implicit Bias Towards Perceived Arab Middle Eastern Muslim Men
Full text linkIn recent decades, prejudices against Arab/Middle Eastern Muslim individuals have risen alongside surging white supremacist hate speech and violence. Perpetrators often subscribe to white supremacist ideology, which overtly supports hate against Arab/Middle Eastern Muslim individuals and attracts followers worldwide. However, research exploring biases against Arab/Middle Eastern Muslim individuals remains limited, leaving gaps in understanding these prejudices and the potential role of white supremacist beliefs. In a pre-registered study involving White non-Hispanic Americans varying in white supremacist beliefs, we examined if these beliefs influenced spontaneous evaluations and hiring bias towards perceived Arab/Middle Eastern Muslim and non-Muslim White men. Results showed negative spontaneous evaluations of perceived Arab/Middle Eastern compared to White men, regardless of white supremacist beliefs. However, those endorsing such beliefs exhibited more explicit hiring biases against Arab/Middle Eastern men, even after accounting for spontaneous evaluations. Thus, while white supremacist beliefs may not heighten implicit biases, they predict explicit biases against perceived Arab/Middle Eastern Muslim individuals
A Meta-analysis of Technology Usage in Word Problem Solving Interventions for Elementary Students: An Application of the SAMR Model
Full text linkThis meta-analysis assessed the effect of the usage of technology in math interventions on the math achievement of students in kindergarten to the fifth grade. The SAMR (Substitution, Augmentation, Modification, Redefinition) (Puentedura, 2006) model was applied to evaluate the degree of technology integration within the math intervention. Twelve group studies met the criteria for inclusion in this meta-analysis. Overall, technology interventions yielded a significant positive effect on the math achievement of elementary-aged students with learning disabilities (LD) (ES = 1.34). While no significant differences in effect sizes were found by function of the SAMR model, the studies that utilize technology as substitutions yielded the highest effect sizes. These findings support the need for continued study into the effects of technology-mediated strategies in word problem solving interventions
Unsettled Ground: How Jewish Undergraduates are Negotiating Identity Shifts and (Un)civil Campus Discourse after October 7
Full text linkThe post–October 7th period has been a period of redefinition for many Jewish American undergraduates and particularly for those who identify as politically left-of-center and who found themselves encountering anti-Israel and antisemitic attitudes among peers and organizations they had been part of previously. Via in-depth interviews with Jewish American undergraduates and their non-Jewish peers, this study documents undergraduates’ realignments of their Jewish and political identities and examines how those identity changes explain the students’ decisions to engage in, or avoid, discussions with peers about October 7, the war in Gaza and the broader Middle East conflict, and/or rising U.S. antisemitism
Effects of Liver Surgery on Drug Transporters in the Liver and Remote Organs
Full text linkAlterations in drug transporters in acute liver failure and chronic liver diseases, such as cirrhosis, have been reviewed before. However, there is a lack of comprehensive reviews on how liver surgery, including transplantation and partial hepatectomy, affects drug transporters. Because ischemia–reperfusion (IR) injury is a hallmark of liver transplantation and most other surgical procedures of the liver, this review focuses on the effects of IR injury, in addition to liver resection, on the expression and function of transporters in the liver and remote organs. Most of the reported studies in this area are carried out in animal models of liver surgeries, with relatively limited data in humans. The results indicate that the effects of IR injury and partial hepatectomy on drug transporters are complex and depend on many variables, such as the species, length and type of ischemia, reperfusion time, and the extent of liver resection. However, for a few major transporters, clear trends have emerged based on both animal and human studies. A major trend is that warm (normothermic) hepatic IR injury or liver transplantation causes overexpression of P-glycoprotein in the liver and remote organs, affecting the pharmacokinetics of substrate drugs. Another observed trend is the relocalization of the liver MRP2/Mrp2 from the canalicular membranes to the cytoplasmic area, reducing the function of the transporter even in the absence of a change in its protein. Alterations in transporter function, such as P-glycoprotein, may significantly impact the pharmacokinetics and pharmacodynamics of drugs in patients undergoing liver surgeries
Generating Predictive Gene Expression Signatures for Alzheimer\u27s Disease Using Postmortem Brain Tissue
No full textBackground: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and tau protein aggregates. These pathological features develop in specific brain regions, but why some areas are more vulnerable to early AD-related changes remains unclear. To address this, predictive gene expression signatures were developed to explore the molecular mechanisms underlying regional susceptibility to AD pathology.
Methods: This was performed using postmortem brain (PMB) tissue from participants in the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) to generate gene expression signatures from six brain regions affected at different stages of AD. These regions included the temporal and frontal lobes, as well as the cerebellum in which differential gene expression analysis identified genes with altered expression patterns. Next, gene expression signatures were developed using the Adaptive Signature Selection and InteGratioN (ASSIGN) toolkit to predict AD activity. These predictions were validated against established neuropathological clinical markers, cognitive assessments, and clinical diagnoses. Dysregulation of key biological pathways was then analyzed using g:Profiler and ClueGO while genetic and sociodemographic factors influence on AD pathology was assessed and drug repurposing candidates were identified using the Connectivity Map (CMAP).
Results: As a result of this analysis, predictive gene expression signatures from six AD-affected brain regions were developed with the ability to distinguish AD activity in control and AD PMB tissue, correlating with clinical disease markers. These signatures revealed common mechanisms underlying regional vulnerability, including upregulation of extracellular matrix (ECM)-related processes and downregulation of hormonal signaling pathways. Notably, upregulation of S100A4 was revealed across all regions, while CRH was downregulated in all but the cerebellum. Additionally, apolipoprotein E (APOE) genotype e3/e4 and male sex influenced disease progression while drug repurposing analysis identified FGFR inhibitors, specifically orantinib, and bromodomain inhibitors as promising therapeutic candidates.
Conclusion: In all, this study highlights molecular signatures associated with regional vulnerability to AD and provides an understanding of genetic and systemic factors influencing disease progression. Key molecular pathways, including ECM-related processes and hormonal regulation, play critical roles in AD susceptibility. The identified drug repurposing candidates offer potential therapeutic avenues for further investigation
Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Remimazolam
No full textRemimazolam, an ultrashort-acting benzodiazepine, has emerged as a promising sedative agent for procedural sedation and general anesthesia. It combines the favorable properties of traditional benzodiazepines with a rapid onset and offset of action, largely due to its unique metabolism via hepatic carboxylesterases rather than cytochrome P450 enzymes. This metabolism allows for predictable pharmacokinetics, reducing the risk of prolonged sedation and drug accumulation, particularly in patients with hepatic or renal impairment. Clinically, remimazolam demonstrates non-inferiority to midazolam and propofol, with advantages including a lower incidence of hypotension and respiratory depression. Multiple randomized controlled trials have shown its efficacy in various procedural settings, including endoscopy and bronchoscopy, with high procedural success rates and faster recovery times compared to midazolam. Additionally, remimazolam is reversible with flumazenil, further enhancing its safety profile. Pharmacokinetic studies indicate a rapid distribution phase, a short terminal half-life of approximately 37–53 min, and a clearance rate significantly higher than midazolam. Pharmacodynamic analyses confirm dose-dependent sedation effects, making remimazolam suitable for tailored sedation levels across patient populations. Special population studies suggest minimal impact of age, renal function, or mild-to-moderate hepatic impairment on drug disposition. However, rare cases of anaphylaxis and re-sedation following flumazenil administration have been reported. Given its rapid onset, predictable clearance, and favorable safety profile, remimazolam represents a valuable alternative to existing sedatives in procedural and anesthetic applications. Further research is warranted to explore its long-term safety, expanded clinical applications, and potential role in high-risk populations
Modeling-based Prediction of Current Oscillation with the Josephson Frequency in Voltage-biased Phase-slip Center Filaments
Full text linkIn this article, we demonstrate that the voltage-biased phase-slip center (PSC) can act as a direct equivalent (not merely an analogy) of the Josephson effect in Josephson junctions (JJs). We analyze the behavior of PSCs in the case when a constant voltage V is applied to the superconducting filament. The analysis is performed using finite element modeling on the basis of time-dependent Ginzburg–Landau (TDGL) equations. It reveals that the current in the filament oscillates with the Josephson frequency ω = 2eV/h. This fact may have important corollaries in practice
Editorial: Molecular Mechanisms of Ion Channel Activation and Modulation
Full text linkIon channels are integral membrane proteins that regulate the passage of ions across cell membranes, thereby shaping processes as diverse as neuronal signaling, muscle contraction, and hormone secretion. Channel activation is typically initiated by a stimulus such as voltage, ligand binding, or mechanical stress that induces conformational changes and opens the channel pore. Beyond activation, channels are subject to fine-tuned modulation by a wide range of endogenous and exogenous agents, from lipids and neurotransmitters to pharmacological drugs. Modulators can stabilize the open, closed, or inactivated states, shift ligand affinities, or alter gating kinetics. Dissecting the structural and dynamic basis of these processes remains central to understanding ion channel physiology and to exploiting channels as therapeutic targets.
This Research Topic brings together studies that illuminate distinct aspects of ion channel activation and modulation, with a particular focus on ligand- and lipid-mediated regulation, redox modulation, and macromolecular channel complexes