Digital Commons Network^™

Tbr2-Dependent Parallel Pathways Regulate The Development Of Distinct Iprgc Subtypes, Takae Kiyama, Ching-Kang Chen, Halit Y Altay, Yu-Jiun Chen, Leviette Sigala, Dan Su, Steven Eliason, Brad A Amendt, Chai-An Mao

Faculty, Staff and Student Publications

The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream …

Leveraging Large Language Models For Heuristic Usability Assessment Of Medical Software: Insights With The Radiation Planning Assistant, Laurence E Court, Jacobus Smit, Lourens Strauss, William Shaw, Andrea Marais, Christoph Trauernicht, Nanette Joubert, Elaine Smith, Shona Badre, Graeme L Lazarus, Thekiso Khotle, Lauren Netherton, Wanda Van Heerden, Carlos Cardenas, Monica Serban, Jan Seuntjens, Christine V Chung, Pavel Govyadinov, Meena Khan, Saurabh Nair, Tucker Netherton, Lifei Zhang

Faculty, Staff and Student Publications

Background: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

Methods: ChatGPT …

Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes …

Venous Thromboembolism In Aggressive B-Cell Lymphoma Patients Treated With Cd19 Car-T Therapy: Single-Institution Study, Neha Venkatesh, Kevin Milligan, Julia Parrish, Yun Qing, Ryan Sun, Paolo Strati, Jeremy Ramdial, Amy Ayers, Sairah Ahmed, Cristhiam Rojas Hernandez

Faculty, Staff and Student Publications

Background: Large B-cell lymphomas (LBCLs) are a common subtype of non-Hodgkin lymphomas. CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized LBCL treatment, with high remission rates but also significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolism (VTE) in CAR-T therapy patients is understudied.

Objective: This study aims to determine the incidence and characteristics of acute VTE in LBCL patients treated with CAR-T therapy and identify baseline clinical features associated with VTE. Methods: We retrospectively reviewed 172 adult LBCL patients treated with CAR-T therapy from January 2018 to November 2019 at MD …

Youth Development Programs Critical Analysis, Rethinking Real Sustainability Measures. Focus On Middle-Eastern And African Contexts., Rasha As Salem

Theses and Dissertations

Abstract Using a systematic review of 18 research papers, policy documents, and evaluation reports, the study examines youth development programs sustainability through four aspects. First, the review explores how definitions of marginalized youth are applied in Middle East and African contexts. Furthermore, the review focuses on how programmatic suitability is discussed and implemented through the concepts of localization and contextualization. Additionally, the importance of locally grounded evidence as much as rigorous evidence and finally the implementation tactics. The review uses frameworks of ecological systems theory and empowering management approaches to analyze the data. The findings reveal significant variation in how …

Integration Of One Health Activities Into Professional Student Education: Successes, Challenges, And Considerations, Karen Gruszynski, Mary Beth Babos, Reagan Bishop, Debra Sullivan, Laroy Brandt

All Faculty and Staff Scholarship

Interprofessional Education (IPE) creates opportunities for multiple disciplines to learn from each other and develop soft skills to improve patient care. One Health similarly emphasizes collaborative and interdisciplinary practice while recognizing the interconnectedness between human, animal, and environmental health. Despite the intersection of IPE and One Health, the meaningful integration of One Health within IPE remains uneven and difficult to operationalize. This perspective synthesizes experiences from multi-college programs implementing One Health-oriented IPE, highlighting successes, challenges, and structural requirements. We argue that for One Health to be successfully integrated into IPE for professional students, it requires extensive logistical planning, coordinated institutional …

Stimuli-Responsive Chemotherapy For Glioblastoma: Sequence-Dependent Synergy Of Cold Atmospheric Plasma And Ultrasound With Cationic Lipo-Doxo, Alessandro Cazzolla

Theses

Glioblastoma (GBM) is an aggressive, infiltrative astrocytic tumour in which pharmacotherapy remains constrained by the blood-brain barrier (BBB) and the heterogeneously altered blood brain tumour barrier, with additional limitations imposed by active efflux and the complexity of the tumour microenvironment. In this setting, externally addressable strategies that modulate transport and uptake at the site of disease are required. A stimuli-responsive chemotherapy platform was developed in which Lipo-DOXO was combined with two non-invasive physical modalities, low-frequency ultrasound (US) and cold atmospheric plasma (CAP), to enhance intratumoural delivery while limiting off-target effects. Liposomes were produced by thin-film hydration followed by a controlled, …

The Affective Economy Of Toxic Atmospheres: Sensory Governance, Ecological Intelligences And The Performative Politics Of Urban Mosquito Management, Orlando Woods, Creighton Connolly

Research Collection College of Integrative Studies

This paper considers how atmospheres can play a powerful role in troubling the management of nature in the multispecies city. It brings the cyclical nature of atmospheric effects, the affective values and il/logics that determine human responses to non-human threats, and the misguided and potentially deleterious health outcomes that ensue into one analytical frame. Drawing on the empirical case of urban mosquito management in Singapore, it considers how the creation of toxic atmospheres through fogging – blowing insecticides into the air in a bid to kill mosquitoes – is ineffective and sets in motion a cascading series of socio-environmental consequences. …

Demographic And Other Correlates Of Non-Prescription Drug Use Among College Students During The Covid-19 Pandemic, Subi Gandhi, Sidketa Fofana, Md Rafiul Islam, Tamer Oraby

School of Mathematical & Statistical Sciences Faculty Publications

Background and objectives: Substance use among college students in the U.S. remains a pressing concern and may have intensified during the COVID-19 pandemic due to increased stress, uncertainty, and academic disruptions. This study investigates the relationship between non-prescription drug use and various demographic, mental health, and behavioral factors among college students during the pandemic's early stages.

Methods: Data were collected through online and in-person surveys in the summer semester of 2021. Behavioral health was assessed using validated instruments: the Patient Health Questionnaire-9 (PHQ-9) for depression and the Drug Abuse Screening Test-20 (DAST-20) for substance use. Demographic and behavioral variables were …

Nested Ecosystems Theory For Conceptualizing Brain Tumors, Lori A Forster, David H Gutmann

2020-Current year OA Pubs

The application of advanced multi-omic methodologies to studying brain tumors has culminated in the appreciation that these cancers function as ecosystems that depend on the interactions of a diverse collection of cell types and signals. This connectivity operates not only at the level of the cancer cell, in which variants create new growth dependencies, but also between tumor cells and the immediate tumor microenvironment, between tumor cells and cell populations residing elsewhere in the brain tissue or body, and in response to extracorporeal factors. The cellular and molecular relationships within these four interrelated strata (intracellular, extracellular, intracorporeal and extracorporeal) act …

Cressent: A Bioinformatics Toolkit To Explore And Improve Ssdna Virus Annotation, Ricardo R Pavan, Matthew B Sullivan, Michael J Tisza

Faculty, Staff and Students Publications

ssDNA viruses are important components of diverse ecosystems; however, it remains challenging to systematically identify and classify them. This is partly due to their broad host range and resulting genomic diversity, structure and rapid evolutionary rates. In addition, distinguishing genuine ssDNA genomes from contaminating sequences in metagenomic datasets (e.g. from commercial kits) has been an unresolved issue for years. Here, we present CRESSENT (CRESS-DNA Extended aNnotation Toolkit), a comprehensive and modular bioinformatic pipeline focused on ssDNA virus 'genome-to-analysis' and annotation. The pipeline integrates multiple functionalities organized into several modules: sequence dereplication, decontamination, phylogenetic analysis, …

Participant Retention In A Prospective Multicenter Cohort Of Participants With Pancreatitis And Factors Associated With Attrition, Radmila Choate, Jun Xu, Jeffrey J Easler, Samuel Han, Anna E Phillips, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Liang Li, Darwin L Conwell, Dhiraj Yadav

Faculty, Staff and Students Publications

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP).

Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate …

Controlled Antibiotic Release From Emulsion-Loaded Alginate And Fibrin Hydrogels Using Ultrasound, Ziba Ghareh Nazi Fam, Asia Winslow, Mario Fabiilli, Sam Varghese, Brian Oeffinger, Flemming Forsberg, Noreen Hickok, Lauren Delaney

Department of Radiology Faculty Papers

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and …

Cytotoxicity Of Ammonia- And Water-Based Silver Fluoride Treatments, Merve Uctasli, Roda Seseogullari-Dirihan, Mustafa Murat Mutluay, Arzu Tezvergil-Mutluay

School of Dentistry Faculty Research and Publications

This study aims to investigate the trans-dentinal and direct cell viability of ammonia- and water-based silver fluoride treatments. Deep dentin discs were prepared, balanced for permeability and autoclaved. Three-dimensional cultures of odontoblast-like cells were transferred to the pulpal aspect of the dentin slices inside perfusion split chambers designed for dentin-barrier cytotoxicity test, following ISO 7405. An experimental resin-based glass ionomer cement and a polyvinylsiloxane impression material served as positive and negative controls, respectively. The experimental treatments included: (i) ammonia-based silver fluoride = SDF, (ii) SDF + potassium iodide = KI, (iii) water-based silver fluoride = SF, and (iv) SF + …

Phenofit: A Framework For Determining Computable Phenotyping Algorithm Fitness For Purpose And Reuse, Laura K Wiley, Luke V Rasmussen, Rebecca T Levinson, Jennnifer Malinowski, Sheila M Manemann, Melissa P Wilson, Martin Chapman, Jennifer A Pacheco, Theresa L Walunas, Justin B Starren, Suzette J Bielinski, Rachel L Richesson

2020-Current year OA Pubs

BACKGROUND: Computational phenotyping from electronic health records (EHRs) is essential for clinical research, decision support, and quality/population health assessment, but the proliferation of algorithms for the same conditions makes it difficult to identify which algorithm is most appropriate for reuse.

OBJECTIVE: To develop a framework for assessing phenotyping algorithm fitness for purpose and reuse.

FITNESS FOR PURPOSE: Phenotyping algorithms are fit for purpose when they identify the intended population with performance characteristics appropriate for the intended application.

FITNESS FOR REUSE: Phenotyping algorithms are fit for reuse when the algorithm is implementable and generalizable-that is, it identifies the same intended population …

Plasma Ceramides Levels In Severe Covid-19 Disease: Correlations With Survival, Tri Pham, Andrea M Heredia Castillo, Andrew Atkinson, Linda R Peterson, M Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Dysregulated inflammatory processes have been associated with severe COVID-19 disease. Ceramides, bioactive lipids involved in inflammatory signaling, have been utilized to predict outcomes in chronic cardiometabolic diseases and pancreatic cancer, but their role in COVID-19 remains unknown.

METHODS: This observational study prospectively enrolled patients with COVID-19 disease who required intubation and mechanical ventilation at a Midwestern academic hospital between August 2020 and March 2021. Plasma ceramides 16:0 (C16), 22:0 (C22), and 24:0 (C24) and inflammatory markers (CRP, ESR, D-Dimer, and ferritin) were collected and organized weekly from symptom onset for up to 6 weeks. Patients were grouped by in-hospital …

The Sport Publication Observational Research Tool (Sport): An Objective Tool To Score The Methodological Quality Of Observational Clinical Sports Medicine Research, Andrew W Kuhn, Paul M Inclan, Ameer A Haider, Michele N Christy, Robert Brophy, Matthew Smith, Matthew J Matava, Et Al.

2020-Current year OA Pubs

BACKGROUND: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases.

PURPOSE: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research.

STUDY DESIGN: Consensus statement.

METHODS: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

Multi-Modal Pediatric Critical Care Datamart For Extracorporeal Support Prediction And Decision Support, Miranda Edmunds, Aditi Gupta, Inez Oh, Levi Kaster, Jonathan Sagel, Andrew Michelson, Yuyao Zhuge, Philip Payne, Ahmed Said

2020-Current year OA Pubs

OBJECTIVES: To develop a multimodal pediatric critical care datamart supporting predictive modeling and decision support tool development, integrating high-resolution physiologic and clinical data and future clinical deployment.

MATERIALS AND METHODS: We developed a continuously expanding datamart integrating electronic health record data, high-resolution telemetry, and extracorporeal membrane oxygenation (ECMO)-domain datasets. The platform links static and longitudinal time-series variables with expert-curated neurologic outcomes for both ECMO and non-ECMO patients, enabling trajectory-based analyses.

RESULTS: The datamart currently includes 25 762 pediatric patients, of whom 395 received ECMO support. The datamart captures granular longitudinal physiologic, laboratory, medication, and telemetry data suitable for dynamic predictive …

Associations Of Child Amygdala Development With Borderline Personality Symptoms During Adolescence, Anna Constantino-Pettit, Kirsten Gilbert, Kiran Boone, Katherine Luking, Benjamin Geselowitz, Rebecca Tillman, Diana Whalen, Joan Luby, Deanna M Barch, Alecia Vogel

2020-Current year OA Pubs

BACKGROUND: The current understanding of the neural correlates of borderline personality disorder (BPD) is limited, but some evidence suggests that alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared to other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. In the current study, we examined childhood trajectories of 2 limbic regions that have been implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms compared to MDD symptoms.

METHODS: Participants (n = …

How To Measure, Analyze, And Interpret Age-Related Changes In Caenorhabditis Elegans: Lessons For Mechanistic And Evolutionary Theories Of Aging, Zuzana Kocsisova, Brian M Egan, Andrea Scharf, Xavier Anderson, Franziska Pohl, Aaron Anderson, Kerry Kornfeld

2020-Current year OA Pubs

Aging is characterized by progressive degenerative changes in tissue organization and function, some of which increase the probability of mortality. Major goals of aging research are to elucidate the series of events that cause degenerative changes, and to identify environmental, pharmacological, and genetic factors that influence these changes; this information might lead to new strategies to extend health span and lifespan. Mechanistic studies of aging depend on accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here, we review studies that describe age-related changes in C. elegans, including measurements of integrated functions such as behavior …

Sequence And Chemical Specificity Define The Functional Landscape Of Intrinsically Disordered Regions, Iris Langstein-Skora, Ryan J Emenecker, Alex S Holehouse, Et Al.

2020-Current year OA Pubs

Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. Whereas sequence specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. …

Seeg-Guided Responsive Neurostimulation To Treat Neocortical Epilepsy: A Multicenter Retrospective Study Of The Efficacy And Safety Of Depth Electrode-Mediated Neuromodulation, Sina Sadeghzadeh, Jon T Willie, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)-guided depth leads to provide responsive stimulation to neocortical gray matter.

METHODS: Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti-responders (≤0%) based on percent seizure reduction at 1 year post-implant (1-Y). …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

Association Of Sleep Disturbance With Survival After Colorectal Cancer Diagnosis: Results From The Colocare Study, Anita R Peoples, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sleep problems are common among cancer patients. The relationship between sleep disruption and clinical outcomes after colorectal cancer (CRC) diagnosis remains poorly understood. We investigated associations of sleep disruption with survival and recurrence in patients with CRC.

METHODS: CRC patients with stages I-IV (N = 895) were included in this study. Self-reported sleep disturbance was assessed presurgery using the sleep item from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core-30 and classified into "no/mild" or "moderate/severe" sleep disturbance. Cox-proportional hazard models were computed (HRs and 95% confidence intervals) to investigate associations of sleep disturbance …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

A Systemic Selective Modified Mrna Delivery Platform For Preventing Chemotherapy-Induced Cardiotoxicity, Jimeen Yoo, Mengcheng Shen, Et Al.

2020-Current year OA Pubs

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac …

Loss Of Beta-Cell Identity And Function As A Mechanism Of Secondary Failure Of Sulfonylurea Therapy In Diabetes, Sumit Patel, Zihan Yan, Maria S Remedi

2020-Current year OA Pubs

Sulfonylureas, commonly used to treat type 2 diabetes (T2D), often lose effectiveness over time when used as monotherapy; however, the underlying mechanisms remain unclear. To investigate the mechanisms of sulfonylurea failure, glibenclamide-releasing pellets were implanted in KK mice, a polygenic model that spontaneously develops T2D. KK mice receiving placebo pellets (KK-Placebo) developed hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Notably, KK mice implanted with glibenclamide (KK-Glib) showed improved blood glucose levels during the first 7 days, returning to KK-Placebo levels thereafter. KK-Glib mice exhibited reduced plasma insulin levels and insulin secretion in response to a glucose challenge compared with the …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

The Tool/Weapon Duality Of Mathematics, Alexandre Borovik

Journal of Humanistic Mathematics

This paper outlines the principal moral and ethical issues of mathematics and existential choices a mathematician may face in his professional life. My text is a manifesto; it is a list of declarations rather than a systematic development of the theme. Indeed each section could be expanded into a paper on its own. I hope to write fairly soon a more detailed exposition.