Duquesne University

There are no cures for neurodegenerative diseases. The biggest hurdle to treating these disorders is that their clinical manifestation is rooted in multiple physiological processes. Therefore, efficacious pharmaceutical options will likely require two or more agents with different mechanisms of action. However, drug combinations have significant drawbacks, including overlapping toxicities and unique pharmacokinetic properties, particularly the rate and extent of central nervous system (CNS) penetration. A single agent with multiple mechanisms of action could overcome these drawbacks. We have recently discovered first-in-class novel single agents (compounds 1 and 2) that mildly inhibit clinically important kinases and subtly favor microtubule stability at concentrations that show no evidence of neuronal toxicity in primary neurons, while maintaining their ability to penetrate the CNS in vivo. It is important to note that the effects of these analogs are mild and are predicated on avoiding neurotoxicity. These multitargeting single agents provide a new structural modality with the potential to influence treatments for Parkinson's and Alzheimer's disease and serve as lead compounds for further optimization.

Higher education institutions (HEIs) are increasingly tasked with meeting the needs of students who hold intersecting identities. Although research has explored support for lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ+) students and autistic students separately, little attention has been given to faculty-level support for individuals who identify as both within HEIs. Because of their direct involvement in students’ academic and personal development, faculty are uniquely positioned to support autistic LGBTQ+ students as they navigate barriers, challenges, and stressors throughout their educational experiences. This article uses a critical narrative review to identify existing research that discuss the barriers, challenges, and stressors faced by each group. Findings are interpreted through a social relational model of disability and frameworks of intersectionality and psychological safety. Practical, faculty-level strategies to promote inclusion and supportive classroom environments for autistic LGBTQ+ students in HEIs are discussed.

Interest in Main Group metal hydrides remains high because of their potential use as hydrogen storage materials and as green catalysts. However, the high reactivity of metal hydrides along with the solvent effects and complex equilibria of condensed phase studies makes study of their intrinsic chemistry a challenge. In principle, the challenge can be overcome by using ion preparation methods such as collision-induced dissociation to synthesize species within the relatively inert gas-phase environment of ion-trapping mass spectrometers. In this study, preparative (ion trap) tandem mass spectrometry (PTMS n ) was used to generate a series of binary, gas-phase metal hydride cations. In particular, we show that the relatively inert environment of a quadrupole ion trap permits (a) the synthesis of discrete, group II metal hydride cations, [MetH] + (Met = Ca, Sr, Ba) and (b) allows for monitoring of intrinsic reactions with neutral species such as H 2 O and CH 2 Cl 2 . When exposed to H 2 O, the [MetH] + cations undergo a hydrolysis reaction to form the respective cationic, metal hydroxides. When allowed to react with CH 2 Cl 2 , two reaction pathways are observed, one leading to formation of [Met(CHCl 2 )] + (with elimination of neutral H 2 ) and the other producing [MetCl] + (by elimination of CH 3 Cl). The reactions to generate the [MetH] + cations, and the ion-molecule reactions with H 2 O and CH 2 Cl 2 , were modeled using density functional theory (DFT) and 2nd – order Moller-Plesset (MP2) calculations to provide optimized structures of reactants, intermediates, products and transition states. In general, the computed enthalpies and free energies for the reactions are in good qualitative agreement with the experimental outcomes. • Preparative tandem mass spectrometry (PTMS n ) is used to generate gas-phase metal hydride cations by collision-induced dissociation of [Met(O 2 C-H)(H 2 O) 2 ] + (Met = Ca, Sr, Ba). • [MetH] + cations hydrolyze to metal hydroxides. With CH 2 Cl 2 , they yield [Met(CHCl 2 )] + via H 2 loss or [MetCl] + via CH 3 Cl elimination. • In general, computed enthalpies and free energies (DFT and MP2) for the reactions are in good qualitative agreement with the experimental outcomes.

Ketamine has emerged as a promising intervention for treatment-resistant mental health disorders, such as depression, anxiety, and posttraumatic stress disorder. With rising global mental health burdens and the limitations of existing pharmacological treatments, ketamine's novel mechanism of action provides a potential alternative for individuals who have not responded to traditional therapies. Ketamine was initially approved by the U.S. Food and Drug Administration in 1970 for use as an anesthetic, and over the past two decades, has increasingly been investigated and used as an off-label treatment for mental health disorders. Additionally, the S-ketamine enantiomer of ketamine, esketamine (marketed as Spravato), received approval for treatment-resistant depression in 2019. Clinical applications of ketamine in the treatment of mental health disorders include intranasal administration (esketamine), IV infusions, ketamine-assisted psychotherapy, and at-home therapy, with varying levels of oversight. The current ketamine landscape has created a perfect storm in which the regulation of ketamine's use in mental health treatment remains fragmented, the evidence is constantly evolving, and a vulnerable population of individuals who are struggling with treatment-resistant mental health symptoms are desperate for relief. This article addresses these considerations by providing a foundation of clinical information that nurses should understand as they advise patients who are receiving, or curious about ketamine, as well as by discussing the regulatory, ethical, and nursing implications of using ketamine in the treatment of mental health disorders.

This paper explores the importance of fidelity in strengthening clinical translation and implementation of rehabilitation research interventions and in reducing unwarranted variation in practice patterns. Fidelity, or accurate and faithful delivery of an intervention, is critical for all aspects of the clinical translational research continuum. Fidelity intentionally defines and tracks the key or active ingredients of a research intervention, ensures adherence to and dose of these key ingredients across therapists and research sites, and clearly establishes what is new or different about an intervention as compared to usual or standard practice. Measurement and reporting standards for fidelity in rehabilitation research vary widely. Historically, rehabilitation researchers have not reported their fidelity process clearly, if at all. This reporting gap creates a multi-faceted conundrum for replication of research findings and eventual clinical implementation of rehabilitation interventions. Without clear fidelity metrics, researchers fail to establish what is novel or unique about an intervention and fail to differentiate a new intervention from other established approaches. Without seeking and applying fidelity metrics, clinicians have no way of replicating a new intervention or understanding which key ingredients replace or supersede old practice habits. Thus, failure of researchers to transparently communicate and of clinicians to understand and apply fidelity metrics widens unwarranted practice variations rather than improving our precision with rehabilitation interventions. Using 2 recent pediatric clinical trials as exemplars, we describe how the development and tracking of metrics defining fidelity for the Sitting Together and Reaching to Play (START-Play) intervention informed key ingredients and program differentiation as researchers moved from an efficacy to an effectiveness trial; and then propose how clinicians might use these same metrics to inform implementation of START-Play. This example will demonstrate how robust fidelity might serve as a common language for successful implementation of and improved precision with rehabilitation research interventions.

Evolving interdependencies across institutions and markets drive systemic financial risk, yet most forecasting models either treat assets independently or rely on static correlation structures. This limitation becomes particularly salient as cryptocurrency markets increasingly interact with traditional banking systems amid financial stress. Ignoring time-varying cross-market network structure risks understating tail risk ‎precisely during periods when accurate systemic risk assessment is most critical. This study proposes a dynamic graph neural network ‎‎(GNN) framework for systemic risk forecasting that models time-varying financial networks spanning banking institutions and major cryptocurrency assets. Nodes represent financial entities, while edges are constructed using rolling-window dependency measures that adapt to ‎changing market conditions. Node dynamics are modeled through temporal neural architectures, and stress regimes are explicitly identified ‎to evaluate performance under market turmoil. The empirical design includes strong temporal baselines, static-graph ablations, and cross-market removal experiments to isolate the contribution of network dynamics and crypto-market integration. Results indicate that a strong ‎LSTM baseline achieves superior volatility forecasting accuracy in both overall and stress-period evaluations, demonstrating the competitiveness of purely temporal models. However, within the class of graph-based models, dynamic GNNs substantially outperform static-graph variants during stress periods, demonstrating the importance of time-varying network structure for capturing volatility amplification. ‎Bank-only and full-system dynamic GNNs exhibit comparable stress-period performance, suggesting that cryptocurrency assets contribute ‎limited incremental information to bank-specific forecasts, while remaining informative for system-level stress characterization. The findings ‎suggest that dynamic graph representations enhance stress sensitivity and structural interpretability relative to static network models, even ‎when they do not surpass strong temporal baselines in raw predictive accuracy. The results support a restrained view of crypto–banking ‎contagion, emphasizing its conditional relevance during periods of market stress rather than unconditional systemic dominance.

This article argues that Friedrich Nietzsche offers a generative contribution to communication ethics through his conception of self-knowledge as a rhetorical and symbolic practice. Drawing especially on The Gay Science and On the Genealogy of Morality , the article interprets Nietzsche’s aesthetic ideal not as moral relativism, but as an ethical demand to become the kind of self who can relate justly. In contrast to rationalist or rule-based ethics, Nietzsche offers a model of intrapersonal justice grounded in coherence, stylistic integrity and symbolic self-formation. The article places Nietzsche in dialogue with communication ethics scholars, rhetorical theorists and the continental tradition, developing a view of justice as responsive presence rather than prescriptive conformity. By doing this, it advances an existential-ethical account of communication as the space where the self becomes answerable to the other. Nietzsche emerges not as an enemy of ethics, but as a thinker of moral formation whose insights deepen our understanding of rhetorical subjectivity and interpersonal responsibility.

Background: Idiopathic developmental intellectual disability (IDID) is a neurodevelopmental disorder that leads to poor health status. This study analyzes the burden of IDID attributed to lead (Pb) exposure in the United States of America (USA) from 1990 to 2023 and projects trends through 2050. Methods: Measurements on Disability-adjusted life years (DALYs) and Years lived with disability (YLDs) were downloaded from the Institute for Health Metrics and Evaluation (IHME). A joinpoint regression model was employed to assess the epidemiological change in this disease. The age-period-cohort (APC) model was used to examine the age, period, and birth cohort effects on DALYs. Decomposition analysis was applied to analyze the role of population, aging, and epidemiological factors in driving changes to DALYs. Bayesian age-period-cohort (BAPC) analysis was conducted to forecast sex-specific burden trends through 2050. Results: From 1990 to 2023, DALYs and age-standardized DALY rate (ASDR) showed an overall decreasing trend. Males bore a higher disease burden than females. In the USA, the average annual percentage change (AAPC) in ASDR was -1.41 (95% CI: -1.45 to -1.37), indicating an overall decline. BAPC analysis predicted that the ASDR will continue to decline for both females and males through 2050, with males showing a faster decline. Conclusions: Consistent efforts have led to significant progress in reducing lead exposure-related IDID in the USA. Prevention strategies focus on continuing to reduce lead exposure and minimize its impact on IDID.

Glycerophosphocholine (GPC) and glycerophosphoinositol (GPI) are phospholipid metabolites generated by phospholipase-mediated deacylation. In budding yeast, they enter cells via the Git1 permease; in fission yeast, the homolog is Tgp1. This study investigates why GPC is toxic to asp1-STF mutants, where Tgp1 is upregulated due to loss of Asp1 pyrophosphatase, resulting in elevated inositol pyrophosphate 1,5-IP8. We show that S. pombe Tgp1 specifically transports GPC, explaining why GPC, but not GPI, impairs growth. Increased GPC uptake slows doubling time but does not reduce viability. Toxicity is relieved by deletion of Gde1, a phosphodiesterase that hydrolyzes GPC to choline and glycerol-3-phosphate. Mutations in either the Gde1 active site or SPX domain also suppress toxicity, and radiolabeling confirms both domains are required for enzymatic activity. GPC is toxic in cells vastly overexpressing Tgp1 even without elevated IP8, but Gde1 loss does not suppress this effect. Similarly, in S. cerevisiae overexpressing the Candida albicans Git3 transporter, GPC provision causes toxicity independent of Gde1. Loss of Gpc1, the acyltransferase converting GPC to lysophosphatidylcholine, does not alter toxicity in either yeast. These findings highlight a conserved process by which GPC regulates growth and reveal a role for IP8 in modulating this process.