University of Louisville

Background Magvad LLC is developing an innovative total artificial heart (TAH) based on a single nutating (nonrotating, “wobbling”) disc pump design to provide up to 8 L/min pulsatile flow at 100 mmHg pressure in children and adults with end‐stage heart failure (HF). We present an early‐stage in vitro study to demonstrate proof‐of‐concept of a nutating disc mechanism for future cardiovascular applications. Methods A commercially available single nutating disc water meter (Recordall, Badger Meter 25–3/4″) was modified and connected to a motor via a shaft coupler and controlled via software to regulate disc “wobbles” per minute. The nutating disc pump was integrated into static and HF‐tuned dynamic mock loops and operated at shaft rotational speeds of 25–225 rpm. Results Pressure–flow ( H – Q ) curves demonstrated the pump generated 7 L/min flow at 100 mmHg (225 rpm). Pump flow, motor work, hemodynamic work, and pump efficiency increased with increasing wobble speed. The pump restored hemodynamics in the dynamic HF mock loop by increasing mean arterial flow and pressure, augmenting pulsatility, and decreasing venous pressure with increasing wobble speed. Conclusions These results demonstrate proof‐of‐concept and very early‐stage feasibility of a single nutating disc to function as a novel low‐speed volume displacement pulsatile flow mechanism for future cardiovascular applications including the development of an innovative TAH.

Despite recognition of the penal system’s impact on HIV vulnerability and known HIV disparities among Black Americans, particularly Black gay and bisexual men, limited research has examined the relationship between incarceration and HIV risk for formerly incarcerated Black men who have sex with men and women (BMSMW). This study aims to fill that gap by exploring the role of masculinity—specifically how both hegemonic and prosocial masculinity may influence sexual risk behaviors. Using data from the Public Health Management Corporation of Philadelphia, we assessed differences in masculinity by incarceration status among BMSMW (n = 239). Multivariate regression analyses tested the relationship between types of masculinity and sexual risk behaviors that increase HIV vulnerability in this population. Results revealed significant differences in masculinity ideology between men with and without incarceration histories. Additionally, different forms of masculinity were found to have varying effects (both positive and negative) on HIV risk. Our findings provide new insights into the complex relationship between incarceration, masculinity, and HIV vulnerability in this high-risk group. The study’s implications include the need for targeted health promotion and education in correctional settings, reentry policy reform, and further research into masculinity’s role in shaping health outcomes for this population. Additionally, there should be a focus on the systemic injustices of incarceration as an area for further exploration to understand its broader impact on health disparities and inequities.

Oxcarbazepine (OXZ) is an antiepileptic drug whose pharmacological effect is primarily mediated by its active metabolite, 10-monohydroxy derivative (MHD). OXZ is approved for use in adults and children older than 2 years with an age- and body weight-tiered dosing recommendation, but dosing guidance for children with obesity is lacking. This work aimed to assess the dosing requirements of OXZ in children with obesity to support label extension. Two multicenter studies (NCT01431326 and NCT02993861) were conducted in patients receiving standard-of-care OXZ therapy. Participants ≥ 2 years of age with a body mass index ≥ 95th percentile were classified as obese. Plasma concentrations were measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. Nonlinear mixed effects modeling was performed using NONMEM 7.4 to characterize the population pharmacokinetics of OXZ and MHD simultaneously. Simulations were performed to compare MHD systemic exposure in children ≥ 2 years of age with and without obesity. One hundred study participants with a median (range) age of 9 years (44 days–20.90 years) contributed 425 plasma concentrations of OXZ (n = 212) and MHD (n = 213). Fifty-two percent of the participants had obesity. A one-compartment joint parent–metabolite model with linear input–output and bi-directional transformation between OXZ and MHD best characterized the pharmacokinetics. Body size was the only covariate affecting pharmacokinetics, and a fat-free mass–based metric termed pharmacokinetic weight (PKWT) best characterized that effect allometrically. Simulation results revealed that the current dosing regimen of OXZ can produce comparable exposure of MHD in children ≥ 2 years of age with and without obesity. A model-informed analysis confirms that the current pediatric dosing regimen of OXZ applies to children in general, regardless of their obesity status.

Background: Periodontal disease (PD) is a primary contributor to tooth loss, which negatively affects oral functionality and quality of life. This research aims to investigate the effectiveness of various machine learning (ML) classifiers in identifying PD among U.S. adults. Method: Nineteen features, selected based on prior literature and expert dentist input, were preprocessed using feature engineering techniques. Eleven machine learning classifiers, including basic and ensemble models, were evaluated to identify the best performing model. The interpretability of the model was evaluated using Shapley additive explanations and individual conditional expectation plots to determine key predictors of periodontitis. Results: The predictive efficacy of the ML classifiers is assessed using metrics such as the area under the receiver operating curve (AUC), accuracy, sensitivity, and specificity. The CatBoost classifier performed best in identifying PD. It achieved an AUC of 84.5%, an accuracy of 75.8%, a precision of 75.8%, a sensitivity of 78.8%, and a specificity of 72.5%. Having an annual dentist visit and age emerged as the most influential variables. Conclusions: The ML models utilized in this study exhibited robust predictive performance and can be further improved by incorporating additional clinical parameters. The proposed models effectively identified individuals at high risk for developing PD.

Polychlorinated biphenyls (PCBs) have been associated with sex-dependent liver disease outcomes. Current mechanisms only partially explain these sex differences and alternative mechanisms including gut-liver toxicity warrant investigation. This study aims to identify PCB-induced changes in the hepatic proteome and gut microbiome and determine their contributions to sex-specific PCB toxicity. Male and female C57BL/6J mice were exposed to Aroclor1260 (20 mg/kg) and PCB126 (20 μg/kg) via oral gavage. After two weeks, hepatic and intestinal tissues were collected for peptide measurements (LC/MS) and 16S sequencing respectively. Proteomic analysis revealed that biological sex largely drove differences seen in the hepatic proteome and dictated PCB liver responses. PCB-exposed females manifested higher abundance of aryl hydrocarbon receptor (AHR) targets including CD36 vs. PCB-exposed males. Computational analysis also demonstrated enhanced AHR and liver-X-receptor (LXR) activation (higher z-scores) in PCB-exposed females vs. males. With regards to gut microbiome, both exposure and sex impacted the composition of microbial communities. Intriguingly, only PCB-exposed males exhibited increased Dehalobacterium abundance, and decreased mRNA levels for genes encoding gut barrier and antimicrobial proteins (Ocln, Reg3g). Overall, PCB-exposed females exhibited an altered proteome relevant to AHR and LXR responses, while PCB-exposed males exhibited more distinct changes in gut microbiota coupled with altered ileal gene expression. The findings suggest that, in addition to biological sex, organ-organ interactions should be considered when predicting toxicity outcomes, particularly for persistent compounds such as PCBs that can impact multiple organs simultaneously yet have tissue-specific toxic effects. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-025-23603-w.

Elevated plasma concentration of lipoprotein(a) is a highly prevalent, independent, and causal risk factor for the development of numerous cardiovascular diseases. This review summarizes the key clinical evidence for elevated lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease, aortic stenosis, and abdominal aortic aneurysm. These data are specifically linked to ongoing developments in understanding the pathophysiological mechanisms of lipoprotein(a) in these contexts. Highly potent lipoprotein(a)-lowering therapies are being studied in cardiovascular outcomes trials for their ability to prevent major adverse coronary events and aortic stenosis progression, potentially ushering in a new era of clinical management of lipoprotein(a).

Objective Diet culture refers to the ubiquitous sociocultural system which conflates bodyweight with health, perpetuates myths about food and eating, and upholds a moral hierarchy of bodies derived from patriarchal, racist, and capitalist forms of domination. Diet culture promotes a hierarchy of bodies and weight‐based moralism that can contribute to anti‐fat bias and the development of eating disorders (EDs). Despite growing recognition of these harms, accessible interventions targeting diet culture beliefs remain limited. In this study, we evaluated a brief, single‐session digital mental health intervention (DMHI) designed to challenge diet culture beliefs (e.g., fat = unhealthy). Method A sample of 455 cisgender women (Mage = 32.6) completed the DMHI, which included psychoeducation and cognitive restructuring techniques aimed at disrupting weight stigma and misinformation about weight and health. Of the 455 participants enrolled, between 284 and 296 completed post‐intervention measures depending on the outcome. Attrition analyses indicated no significant baseline differences between completers and non‐completers on ED pathology or weight stigma variables; the only exception was the interpersonal relationships subscale of fat acceptance, where non‐completers reported slightly lower baseline scores. Pre‐ and post‐intervention assessments measured ED pathology, fat acceptance, and anticipated weight stigma. Results We found increased fat‐accepting health beliefs and decreased fear of weight stigma and ED symptoms, specifically fear of weight gain, following the intervention. However, interpersonal respect for fat individuals slightly decreased, and fat activism showed limited improvement, suggesting that certain components of fat acceptance may require more sustained or relational formats. Discussion These findings highlight the potential of DMHIs to shift belief systems related to diet culture and ED risk, particularly as scalable, low‐barrier tools for prevention and early intervention. Future work should examine the durability of effects and test enhancements targeting activism and interpersonal change. Hypotheses, variables, and analyses were pre‐registered at https://osf.io/27ym3.

Charge storage by oxide anion intercalation into oxide materials has been recently demonstrated. In an effort to further expand this field beyond 3D systems, we have investigated this effect in quasi‐2D oxides LaSrCu0.5Mn0.5O4 and LaSrZn0.5Mn0.5O4. The structure of these materials consists of octahedral (Cu/Mn)O6 or (Zn/Mn)O6 units, forming 2‐dimensional layers, while La/Sr are located in the gaps between those layers. The spaces within the structure are expected to support the intercalation of the oxide anion. We first undertook half‐cell measurements in a three‐electrode setup and analyzed the contributions from capacitive and diffusive processes to the observed current in electrochemical measurements. We then assembled symmetric full cells using these materials and conducted galvanostatic charge–discharge studies, which showed greater pseudocapacitive properties for LaSrCu0.5Mn0.5O4 compared to LaSrZn0.5Mn0.5O4. Considering that the two materials are isostructural, a correlation between pseudocapacitive activity and charge transfer resistance was demonstrated. The energy density obtained from the symmetric cell of LaSrCu0.5Mn0.5O4 was superior to that of LaSrZn0.5Mn0.5O4, as well as those reported for several previously studied systems that operate based on oxide anion intercalation. In addition, symmetric cells of both materials were tested for at least 6000 cycles to examine the stability of these materials.

OBJECTIVE To evaluate inhaled technosphere insulin (TI) in children with diabetes. RESEARCH DESIGN AND METHODS 230 youth 4–17 years old with type 1 (98%) or type 2 (2%) diabetes treated with multiple daily injections of insulin were randomly assigned 1:1 to TI or rapid-acting analog (RAA) insulin plus continuation of long-acting basal insulin and continuous glucose monitoring (CGM) for 26 weeks. The primary outcome was change in HbA1c, tested for noninferiority with margin of 0.4%. RESULTS In intent-to-treat analysis, mean HbA1c (% ± SD) was 8.22 ± 0.87 at baseline and 8.41 ± 1.38 at 26 weeks with TI and 8.21 ± 0.96 and 8.21 ± 1.10, respectively, with RAA (adjusted difference = 0.18; 95% CI −0.07, 0.43; noninferiority P = 0.091). CGM-measured time in range 70–180 mg/dL was not significantly different between groups (adjusted difference −2.2%; 95% CI −7.0, 2.7; P = 0.38). Two severe hypoglycemic events occurred in the TI group and one in the RAA group. Change in forced expiration volume in 1 s from baseline to 26 weeks did not differ comparing TI and RAA (P = 0.53). The TI group reported greater treatment satisfaction (P = 0.004) and had less gain in weight and BMI percentile (P = 0.009) than did the RAA group. CONCLUSIONS The primary analysis did not meet the prespecified criteria for HbA1c noninferiority. However, TI use was safe over 26 weeks without affecting pulmonary function and was associated with greater treatment satisfaction and less weight gain compared with RAA, supporting TI as a treatment option for some pediatric patients with type 1 diabetes.

Background Self-directed learning has been considered as an effective training method for students and professionals in the healthcare setting. This study aims to assess the level of self-directed learning readiness among paramedic students in Jordan and identify any associated factors. Methods This cross-sectional descriptive study utilized an online self-administered questionnaire. The study was conducted across three academic institutions in Jordan offering paramedic programs. A sample of paramedic students was assessed using the Self-Directed Learning Readiness Scale. All enrolled paramedic students at the three institutions were included as potential participants. Differences between group means were analyzed using a Student’s t-test and one-way analysis of variance, as appropriate. Results A total of 529 participants completed the questionnaire. The majority of participants were male (56.1%) with a mean age of 21.2 (SD ± 2.96). The overall mean score of the scale was 141.9 (SD ± 35.5) and a total of 302 (57.1%) participants had a high level of self-directed learning readiness (score > 150). Students with a high level of self-directed learning readiness were more likely to be male (p = 0.039) and have high academic performance levels (p = 0.006). Conclusions This study found that, although most participants achieved a high level of self-directed learning readiness, the overall mean score was among the lowest in the reported literature. Therefore, it is essential to develop improvement plans to encourage and enhance self-directed learning skills for both students and faculty members.

Objective We aimed to determine if omega‐3 fatty acid (FA) supplementation significantly reduces cardiovascular (CV) events in patients with established CV disease or at high CV risk. Methods We conducted a comprehensive literature search on PubMed, Embase and Cochrane CENTRAL. The results of our analyses were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and pooled using a random effects model. Meta‐regression bubble plots were generated to visualise the results of the analysis, while the detailed results were tabulated. A p‐value less than‐.05 was considered significant in all cases. Results A total of 42 studies (176 253 participants) were included in our analysis. The pooled analysis demonstrates that omega‐3 FA are associated with a significant reduction in CV mortality (p =‐.02), CV disease (p =‐.03), coronary heart disease (CHD) (p =‐.007), myocardial infarction (MI) (p =‐.008), fatal MI (p =‐.0004) and revascularisation (p =‐.003), and a significant increase in atrial fibrillation (p =‐.01), and gastrointestinal (GI) adverse events (p =‐.02). Subgroup analysis demonstrated a significant improvement with EPA monotherapy compared to EPA+DHA combination therapy in the risk of CV mortality (p = 0.01), CVD events (p <‐.00001), MACE (p < .00001), CHD (p < .00001), MI (p <‐.00001), fatal MI (p =‐.004) and revascularisation (p <‐.0001). EPA monotherapy was associated with a significant increase in the risk of atrial fibrillation (p =‐.01). Regression analysis demonstrates a dose–response relationship between omega‐3 FA (EPA or EPA+DHA) and CVD events (p =‐.001), CHD (p =‐.035), revascularisation (p =‐.035) and ischemic stroke (p =‐.003). Conclusion Our study demonstrated a significant reduction in the risk of cardiovascular outcomes with omega‐3 FA administration.

This paper proposes a novel, node-splitting support vector machine (SVM) for creating survival trees. This approach is capable of nonlinearly partitioning survival data when the data includes continuous, right-censored outcomes. Our method improves on an existing non-parametric method, which uses oblique splits to induce survival regression trees. In this prior work, these oblique splits were created via a non-SVM approach, by minimizing a piecewise linear objective function, called a dipole splitting criterion, constructed from pairs of covariates and their associated survival information. We extend this method by enabling splits from a general class of nonlinear surfaces. We achieve this by ridge regularizing the dipole-splitting criterion to enable application of kernel methods in a manner analogous to classical SVMs. The ridge regularization provides robustness and can be tuned. Using various kernels, we induce both linear and nonlinear survival trees to compare their sizes and predictive powers on real and simulated data sets. We compare traditional univariate log-rank splits, oblique splits using the original dipole-splitting criterion, and a variety of nonlinear splits enabled by our method. In these tests, trees created by nonlinear splits, using polynomial and Gaussian kernels, show similar predictive power while often being of smaller sizes compared to trees created by univariate and oblique splits. This approach provides a novel and flexible array of survival trees that can be applied to diverse survival data sets.

The approval of disease-modifying treatments for Alzheimer's disease demands a rethinking of cognitive screening. Drawing on over 180 stakeholder interviews from the NSF National I-Corps program, this perspective highlights barriers in current workflows, from time constraints in primary care to learning effects in long-term care, and presents innovation pathways centered on AI and digital biomarkers. Speech analysis, in particular, offers a scalable and cost-effective screening tool aligned with existing CPT codes. We outline implementation strategies and emphasize the urgent opportunity to align technological innovation with frontline clinical needs to ensure advances translate into meaningful patient and provider benefit.

Sphingolipids play a crucial role in gut inflammation. Neutral ceramidase (NcDase) serves as a pivotal regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of intestinal epithelial cells (IEC) NcDase to colitis is not well understood. Here, a protective mechanism by which IEC NcDase deficiency (Asah2ΔIEC) and its‐related gangliosides prevent dextran sulfate sodium (DSS)‐induced colitis in mice is described. Asah2ΔIEC mice display reduced susceptibility to DSS‐induced colitis and increase regulatory T (Treg) cells compared to Asah2fl/fl littermates. Deletion of IEC NcDase induces the upregulation of sialyltransferase ST8SIA1 and promotes the sialic‐acid‐containing ganglioside GD3 production. Siglec‐E is a sialic‐acid‐binding lectin expresses predominantly on myeloid cells. Mechanistically, it is identified that GD3 is a functional ligand for Siglec‐E on macrophages and found that GD3/Siglec‐E interaction induced a rapid metabolic rewiring of macrophages that involved the production of IL‐33, which contributes to the generation of ST2⁺Foxp3⁺ Treg cells. Finally, deletion of ST8SIA1 or administration of dietary GD3 induces or reduces mucosal inflammation, respectively. This work defines a critical role for ganglioside GD3 in the induction of colonic Treg cells and identifies an activating pathway that follows engagement of Siglec‐E.