Des Moines University

Hematologic malignancies remain a significant public health concern in the United States, affecting over 1.5 million individuals. Although chemotherapy remains a foundational component of treatment, the emergence of novel therapeutic strategies has transformed the treatment landscape. This review examines the development, mechanism of action, expanding clinical applications, and barriers to care associated with chimeric antigen receptor T-cell (CAR T-cell) therapy. Relevant data was found via a literature search across major biomedical databases focusing on current clinical implementation of CAR T-cell therapies. To date, seven CAR T-cell therapies have received U.S. Food and Drug Administration approval, demonstrating robust response rates and effective clearance of malignant cells in hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia. Despite these promising outcomes, CAR T-cell therapy faces significant challenges, including manufacturing timelines, geographic access limitations, and substantial financial burden. As the field continues to evolve, this review aims to provide clinicians with an updated synthesis of clinical outcomes, treatment-related toxicities, and persistent barriers to equitable access.

Bladder cancer is one of the most common urological malignancies, with 5-year survival rates below 40% in advanced cases. Oncologic immunotherapy has become a popular approach to treating cancer and programmed death ligand 1 (PDL1), programmed death ligand 2 (PDL2), intercellular adhesion molecule 2 (ICAM2) and 4-1BB ligand (4-1BBL) are key costimulatory molecules in oncologic immunotherapy. Previous research has shown plant phytochemicals can act as immunomodulators by regulating costimulatory functions to increase T-cell activation and thus to inhibit malignant proliferation. However, the role of Aloe vera in the growth of bladder cancer and in the expression of these key costimulatory molecules has not been elucidated yet. This study is designed to investigate if Aloe vera could have a role in the growth of bladder cancer and if it has any effect on the expression of these key costimulatory molecules in bladder cancer. Clonogenic survival assay and immunohistochemistry (IHC) for PCNA staining were used to evaluate growth of a widely used bladder cancer cell line, T24, in the presence or absence of Aloe vera extract (AE). RT-PCR and IHC were performed to investigate the expression of important costimulatory molecules PDL1, PDL2, ICAM2, and 4-1BBL. Clonogenic survival assay showed a reduction in the percentage of bladder cancer cell colonies, and this result was supported by decreased PCNA staining intensity upon treatment with AE. RT-PCR revealed decreased expression levels of PDL1 and PDL2, which are pro-oncogenic costimulatory molecules and increased expression levels of ICAM2 and 4-1BBL, which are anti-oncogenic costimulatory molecules. Their expression levels were further supported by IHC staining. Aloe vera inhibits bladder cancer growth. Aloe vera upregulates the expression of ICAM2 and 4-1BBL and downregulates the expression of PDL1 and PDL2.

We propose a finite, probabilistic, and algebraic formulation of quantum gravity based on the Chrono-Emergence (CE) emergence law and the Discrete-State Time Density (DTD) field ˆt. This framework reinterprets gravity as being driven by elastic strain in the ˆt field. We derive a finite critical time density, ˆt crit = 2π/c, at which spacetime enters a dense-time phase, suppressing coherent wave transport and black body radiation. This mechanism defines the Chrono-Quantum Mirror (CQM), a finite phase boundary that replaces the classical event horizon and supplants the evaporation paradigm. We define the Timeon Lattice Potential (TLP) and the Chrono-Emergent Tunneling (CET) mechanism as the microscopic drivers for matter-confinement within this field. Cosmologically, we propose a multiverse lattice of interacting domains, where the Lattice Gravitational Strain (LGS) from causal bleed manifests as dark matter, and the expansionary momentum from a cyclical Chrono-Shear Event manifests as dark energy. This cycle culminates in a final, acausal deconfinement and reconvergence of matter-energy that seeds the next domain’s causal onset phase. We propose distinct, falsifiable experiments to test the theory. The result is a unitary, thermodynamically closed, and observationally-grounded ecosystem of solutions for foundational physics termed Timeon Lattice Multiverse Cosmology

Traumatic injuries represent a significant public health challenge, affecting millions worldwide annually and necessitating acute pain management that frequently involves the use of opioid analgesics to mitigate discomfort and facilitate recovery. Although opioids remain an integral part of post-traumatic injury pain management, their use exposes trauma survivors to the risk of developing persistent use, misuse, or opioid use disorder (OUD). Pre-injury health determinants, such as age, gender, psychiatric conditions, medical conditions, and substance use history, may interact with injury-related factors to acutely escalate the risk for misuse and addiction. Despite the growing recognition of these potential vulnerabilities, there remains a lack of evidence-based clinical decision support on modifiable and non-modifiable risk factors specific to post-traumatic injury opioid risk trajectories. This review summarizes the literature related to the multifactorial contributors to opioid misuse and addiction following traumatic injury such as patient-level (e.g., demographics, behavioral health), injury-related (e.g., severity, type), and system-level (e.g., prescribing patterns) characteristics. A comprehensive literature search, inclusive of the literature from 1995 to November 2025, was performed in PubMed/MEDLINE, Scopus, and Google Scholar using combinations of terms related to "opioids," "misuse," "addiction," "trauma," and "injury." Search keywords and operators were developed in collaboration with a university librarian. Reference lists of articles were searched and synthesized. Case reports, case series, editorials, mini-reviews, letters to editor without original data, and qualitative studies were excluded. The findings of the review are expected to provide insight into clinical-decision making as it relates to the management of pain, pain-related distress and functional impact, and co-occurring conditions that may impact injury-related outcomes and the potential likelihood of substance misuse and addiction.

To develop a proof-of-concept automated framework for integrated intraoperative transesophageal echocardiography (TEE) interpretation, encompassing view classification, left ventricular ejection fraction (LVEF) and right ventricular systolic function (RVSF) assessment, and tricuspid regurgitation (TR) grading. This cross-sectional study used TEE video clips and reports from patients undergoing cardiac surgery from 2018 to 2023. Two hospitals within the University of Pennsylvania Healthcare System. Study participants were ≥18 years of age and undergoing any cardiac surgery in which an intraoperative TEE was performed. We used 6,900 intraoperative TEE studies from 6,016 unique patients. Receipt of intraoperative TEE examination during cardiac surgery. The view classification model was trained on TEE clips from 1,432 studies, and the diagnostic model was trained on clips from 6,400 studies, for a total of more than 700,000 individual TEE clips for training. Performance was evaluated on 945 test clips from 8 studies for view classification and 500 studies for diagnostic prediction. No external testing was performed. The view classifier achieved 86% accuracy compared to the expert agreement top-1 weighted accuracy of 74%. The diagnostic model differentiated LVEF >55% versus ≤55% (area under the receiver operating characteristic curve [AUROC] = 0.86) and LVEF >30% versus ≤30% (AUROC = 0.95). Continuous LVEF prediction was assessed (Pearson r = 0.79, mean absolute error = 7.8). The model differentiated normal versus abnormal RVSF (AUROC = 0.82) and differentiated less-than-moderate versus moderate-or-greater right ventricular dysfunction (AUROC = 0.92). Additionally, the model differentiated no TR versus any TR (AUROC = 0.69) and differentiated less-than-moderate versus moderate-or-greater TR (AUROC = 0.79). This proof-of-concept automated approach showed encouraging results for view classification and quantification tasks, suggesting potential for further development toward intraoperative utility.

Dysregulated enhancer activity disrupts gene expression, contributing to disease. However, the structural and functional complexity of enhancers hinders their characterization. Here, we investigate a cis-regulatory element upstream of matrix metalloproteinase-9 (MMP9), a gene implicated in cancer, cardiovascular disease, inflammation, and pregnancy complications. Using luciferase assays and CRISPR-Cas9 mediated knockout in a human placental cell line, we define a one kilobase segment that enhances MMP9 expression. Further dissection reveals two activating sub-segments and, unexpectedly, one repressive sub-segment. Molecular assays suggest transcription factors that mediate these opposing effects. This work adds to the growing understanding that enhancers can integrate both activation and repression, revealing a more complex regulatory architecture than previously appreciated. Together, these findings underscore the importance of enhancer dissection for understanding gene regulation across tissues and diseases.

Abstract Quality modern colorectal surgery education demands more than simply teaching technical skills; it requires a deep understanding of how surgeons learn. This article explores foundational pedagogical theories that support effective instruction across all stages of surgical training. Cognitive load theory, behaviorist models, and constructivist approaches such as experiential and social learning are examined for their relevance to surgical education. Deliberate practice and mastery learning frameworks offer structured methods for developing procedural expertise. Teaching strategies such as simulation and feedback models are discussed to promote competence and autonomy. Additionally, the article considers emotional and motivational components of learning, highlighting the roles of self-efficacy, feedback, and reflective practice. By aligning educational practice with established theory, colorectal surgeons can more effectively train future colleagues and elevate standards of care, professionalism, and continuous learning in a dynamic healthcare landscape.

ABSTRACTImportancePlantar heel pain (PHP) contributes to reduced quality of life and is costly to manage. Persons with PHP are infrequently referred to a physical therapist after presenting to primary care or podiatry.ObjectiveThe study objective was to compare the cost-effectiveness of usual podiatry care (uPOD) plus physical therapist treatment with that of uPOD alone in the management of PHP.DesignA cost-effectiveness analysis from societal and health care sector perspectives and a 3-year time horizon was performed alongside a randomized clinical trial. Intention to treat was used as the base case, and sensitivity analyses were used to assess the impact of adherence to treatment (ie, per protocol) and PHP-specific costs.SettingThe setting was a multidisciplinary outpatient clinic in the United States.ParticipantsParticipants were 95 eligible patients with PHP.InterventionsuPOD consisted of a stretching handout, medication, injections, and orthotics; uPOD plus physical therapist treatment also included physical therapist intervention consisting of manual therapy, exercise, foot taping, and iontophoresis.Main Outcomes and MeasuresCost-effectiveness was determined by between-group differences in costs relative to quality-adjusted life-years (QALYs). Cost-effectiveness at different thresholds of decision maker willingness to pay was illustrated using the cost-effectiveness acceptability curve.ResultsuPOD plus physical therapist treatment reduced societal costs by $2708 (95% CI = −$294 to $5709) relative to uPOD and increased QALYs by 0.09 (95% CI = −0.01 to 0.18). The cost-effectiveness acceptability curve demonstrated 98%, 99%, and 97% probabilities of cost-effectiveness of uPOD plus physical therapist treatment in the base-case, per-protocol, and PHP-specific cost analyses using a willingness-to-pay threshold of $50,000 per QALY.ConclusionsAdding physical therapist treatment to uPOD lowered total costs and improved quality of life despite increased short-term health care utilization. Results were not altered when considering adherence to treatment or PHP-specific costs.RelevanceThis study informs shared decision-making between providers and patients with PHP about the costs and benefits of adding physical therapist treatment and provides support for the economic value of physical therapist treatment for PHP.