Digital Commons Network^™

Integrase-Deficient Lentiviral Vector As A Platform For Efficient Crispr/Cas9-Mediated Gene Editing For Mucopolysaccharidosis Iva, Fnu Nidhi, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder causing systemic skeletal dysplasia due to a deficiency of N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) enzyme activity, leading to the impaired degradation and accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate. While treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available, they have significant limitations regarding efficacy in skeletal tissues and long-term safety, highlighting the need for more effective therapies. We evaluated a novel gene therapy approach using a dual Integrase-deficient lentiviral vector (IDLV) to deliver an expression cassette that includes human GALNS cDNA and Cas9 sgRNA, …

Pi(4)P Recruits Cide Proteins To Promote The Formation Of Unilocular Lipid Droplets During Adipogenesis And Hepatic Steatosis, Jin Wu, Mingming Gao, Xiaoqin Wu, Yang Liu, Taiping Zhang, Yan Liang, Haixia Yang, Chengxin Ma, Youpi Ye, Chunmei Chang, Peng Li, Feng-Jung Chen, Hongyuan Yang

Faculty, Staff and Student Publications

Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. The composition of LD surface phospholipids and their impact on LD growth and function remain to be defined. Phosphoinositides mark cellular organelles and regulate organellar function. Here, we demonstrate that PI(4)P decorates a subset of LDs to recruit and activate CIDE proteins. Enhanced expression of ORP2 and ORP5, LD-associated lipid transfer proteins that remove PI(4)P from LDs, abolished the localization and function of CIDE proteins. Blocking the synthesis of PI(4)P on the LD surface …

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Mtor Signaling Regulates The Development Of Airway Mucous Cell Metaplasia Associated With Severe Asthma, Katrina M. Kudrna, Luis F. Vilches, Evan M. Eilers, Shailendra K. Maurya, Steven L. Brody, Amjad Horani, Kristina L. Bailey, Todd A. Wyatt, John D. Dickinson

2020-Current year OA Pubs

In asthma, airway epithelial remodeling is characterized by aberrant goblet cell metaplastic differentiation accompanied by epithelial cell hyperplasia and hypertrophy. These pathologic features in severe asthma indicate a loss of control of proliferation, cell size, differentiation, and migration. MTOR is a highly conserved pathway that regulates protein synthesis, cell size, and proliferation. We hypothesized that the balance between MTOR and autophagy regulates mucous cell metaplasia. Airways from individuals with severe asthma showed increased MTOR signaling by RPS6 phosphorylation, which was reproduced using an IL-13-activated model of primary human airway epithelial cells (hAEC). MTOR inhibition by rapamycin led to a decrease …

Overexpression Of Tsg101 Causes The Development Of Adenosquamous Mammary Carcinoma, Rayane Dennaoui, Patrick D. Rädler, Madison N. Wicker, Kerry Vistisen, Rosa-Maria Ferraiuolo, Aleata A. Triplett, Hridaya Shrestha, Tessa A. Liner, Karoline C. Manthey, Hallgeir Rui, Robert D. Cardiff, Teresa M. Gunn, Charles M. Perou, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The mammalian Tumor Susceptibility Gene 101 (TSG101) encodes a protein with diverse functions that control the proliferation and survival of cells, but its role in malignant transformation and cancer development has remained enigmatic.

METHODS: To study the pro-tumorigenic functions of TSG101, we developed a bi-transgenic mouse model that expresses exogenous TSG101 along with a luciferase reporter in a ligand-controlled manner in the mammary gland epithelium. We performed a comprehensive histopathologic, biochemical, and molecular characterization of ductal hyperplasia and mammary tumors. Unsupervised hierarchical clustering based on 1,723 intrinsic genes of ten TSG101-overexpressing cancers alongside 251 tissue samples representing 31 reference …

The Landscape Of Autosomal-Dominant Alzheimer's Disease: Global Distribution And Age Of Onset, Haiyan Liu, Thomas W Marsh, Xinyu Shi, Kevin M Bowling, Ellen Ziegemeier, Guoqiao Wang, Yuchen Cao, Alexa Dickson, Richard J Perrin, Michelle Doering, Alisha Daniels, Brian A Gordon, Tammie L S Benzinger, Jason Hassenstab, Laura Ibanez, Charlene Supnet-Bell, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Carlos Cruchaga, Eric Mcdade, Jorge J Llibre-Guerra, Et Al.

2020-Current year OA Pubs

We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying …

Coresh: A Gene Signature-Based Search Engine For Public Gene Expression Datasets, Vladimir Sukhov, Aigul Nugmanova, Yury Vorontsov, Parul Mehrotra, Maksim Kleverov, Kodi Ravichandran, Maxim Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

Public data repositories like Gene Expression Omnibus (GEO) contain an extensive amount of data from hundreds of thousands of experiments, making them a valuable resource for researchers. A common scenario for utilizing this resource is to show transcriptional similarity of one's own data to a public dataset as evidence of potentially similar biology. However, when searching for such datasets, researchers are usually limited to keyword-based search, which requires having a specific hypothesis and relies on the presence of high-quality metadata in public datasets. Here, we introduce CORESH, a web server designed to systematically find GEO datasets that match a user-provided …

Artificial Intelligence Policies In Bioethics And Health Humanities: A Comparative Analysis Of Publishers And Journals, Christopher Bobier, Daniel Rodger, Daniel Hurst

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Rapid advancements in artificial intelligence (AI) pose novel ethical and practical challenges for scholarly publishing. Although AI-related policies are emerging in many disciplines, little is known about the extent and clarity of AI guidance in bioethics and health humanities journals.

METHODS: A search of publicly available journal lists from the American Society for Bioethics and Humanities, Health Humanities Consortium, and Association for Medical Humanities was supplemented with Google Scholar's top 20 bioethics journals ranked by h5-index. This yielded 54 unique journals, of which 50 remained after excluding those without a functional website or recent publications. AI policies were reviewed …

Direct Inhibition Of Ras Reveals The Features Of Oncogenic Signaling Driven By Ras G12 And Q61 Mutations, Michelangelo Marasco, Dinesh Kumar, Santiago Garcia Borrego, Tessa Seale, Giulia Maddalena, Riccardo Mezzadra, Kylie Belanger, Soren Cole, Brayan Perez, Wei Luan, Radha Mukherjee, Ilinca Aricescu, Vladimir Markov, Yuxin Zhu, Sabrina Arena, Alberto Bardelli, Elisa De Stanchina, Scott W Lowe, Richard A Burkhart, Jacquelyn W Zimmerman, Rona Yaeger, Scott E Kopetz, Neal Rosen, Sandra Misale

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer, often at codons 12 and 61. With the recent introduction of RAS inhibitors, we can now directly investigate the effects of specific RAS mutations in cancer cells. In this study, we demonstrate that in tumors with RASG12X mutations, mutant RAS can be activated by receptor tyrosine kinases (RTK), and PI3K activation is dependent on mutant RAS. Conversely, RASQ61X mutations activate the MAPK cascade independently of RTKs, and inhibition of RASQ61X impairs MAPK pathway activation but leaves the PI3K pathway unaffected. Our characterization of these distinct features of G12X and Q61X mutations suggests that …

Amino Acid Transporter Lat1 (Slc7a5) Promotes Metabolic Rewiring In Tnbc Progression Through The L-Trp/Qprt/Nad+ Pathway, Margot Y. Fedoroff, Lei Zhao, Shaomin Wang, Alok Bhushan, Haifeng Yang, Karen M. Bussard, Stephen C. Peiper, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Cancer cells uptake excessive nutrients by expressing higher levels of glucose and/or amino acid transporters to meet their increased energy demands. L-type amino acid transporter 1 (LAT1), is regarded as a cancer-specific transporter for the uptake of large neutral amino acids such as L-tryptophan. However, the mechanism by which LAT1 rewires cellular metabolism to promote cancer progression and chemoresistance have not yet been investigated.

METHODS: The protein levels of LAT1, p-PKM2, and p-LDHA were determined in breast cancer tissue arrays by immunohistochemistry staining followed by survival analysis. The orthotopic breast cancer models in mice, syngeneic breast cancer models, and …

Hallmarks Of Stem Cell Aging, Thomas A Rando, Anne Brunet, Margaret A Goodell

Faculty, Staff and Students Publications

As organisms age, somatic stem cells progressively lose their ability to sustain tissue homeostasis and support regeneration. Although stem cells are relatively shielded from some cellular aging mechanisms compared with their differentiated progeny, they remain vulnerable to both intrinsic and extrinsic stressors. In this review, we delineate five cardinal features that characterize aged stem cells and examine how these alterations underlie functional decline across well-studied stem cell compartments. These hallmarks not only provide insight into the aging process but also serve as promising targets for therapeutic strategies aimed at rejuvenating stem cell function and extending tissue health span.

Irradiation Of Prostate Cancer Alters Circulating Small Extracellular Vesicle Functions, Aejaz Sayeed, Vaughn Garcia, Cecilia E. Verrillo, Rachel M. Derita, Md Niamat Hossain, Shiv R. Krishn, Samuel Sey, Christopher D. Shields, Adrian D. Altieri, Qin Liu, Khalid Sossey-Alaoui, William K. Kelly, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active …

Immature Acta2r179c/+ Smooth Muscle Cells Cause Moyamoya-Like Cerebrovascular Lesions In Mice Prevented By Boosting Oxphos, Anita Kaw, Suravi Majumder, Jose E Esparza Pinelo, Ting Wu, Zbigniew Starosolski, Zhen Zhou, Albert J Pedroza, Xueyan Duan, Kaveeta Kaw, Angie D Gonzalez, Ripon Sarkar, Michael P Fischbein, Philip L Lorenzi, Lin Tan, Sara A Martinez, Iqbal Mahmud, Laxman Devkota, L Maximilian Buja, Heinrich Taegtmeyer, Ketan B Ghaghada, Sean P Marrelli, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

ACTA2 pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusions of the distal internal carotid arteries, but the mechanisms of pathogenesis are unknown and no preventive treatments exist. Here we show that Acta2R179C/+ smooth muscle cells (SMCs) fail to fully differentiate and maintain stem cell-like features, including increased migration and glycolytic flux compared to wildtype (WT) SMCs. Increasing mitochondrial respiration with nicotinamide riboside (NR) drives differentiation and decreases migration of Acta2R179C/+ SMCs. Carotid artery injury of Acta2SMC-R179C/+ mice leads to premature death, intraluminal SMC accumulation leading to MMD-like occlusive lesions, neurologic symptoms, …

Evaluation Of The Feasibility And Effectiveness Of Trauma-Focused Cognitive Behavioural Therapy For Children And Youth In Ukraine During The War, Elisa Pfeiffer, Maike Garbade, Renee Beer, Anette Birgersson, Natalie Cabrera, Judith A Cohen, Esther Deblinger, Rafaela Gjini, Veronica Kirsch, Zlatina Kostova, Michael Larsson, Anthony Mannarino, Gavin Moffitt, Marja Onsjö, Tale Ostensjo, Anna Vikgren, Hanna Weyler, Vitalii Klymchuk, Cedric Sachser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The large-scale Russian invasion of Ukraine in early 2022 resulted in a humanitarian crisis with hundreds of thousands of children exposed to traumatic events. To date, trauma-focused evidence-based treatments (EBTs) for children and youth have not been systematically evaluated and implemented in Ukraine. This study aims at evaluating 1) the feasibility of a training program for Ukrainian therapists on Trauma-Focused Cognitive Behavioural Therapy (TF-CBT) and 2) the feasibility and effectiveness of the treatment for children, youth, and their families in and from Ukraine during the ongoing war.

METHODS: The project "TF-CBT Ukraine" was implemented between March 2022 and May …

Teaching Pathographies Of Mental Illness, Nathan Carlin, Angela Gomez, Margarita Ortiz

Faculty and Staff Publications

This paper describes the content and evolution of a fourth-year course for medical students on teaching pathographies of mental illness. (It is a follow-up to Nathan Carlin's Pathographies of Mental Illness that appeared as an Element in the Bioethics and Neuroethics series published by Cambridge University Press.) The course originally centered on classic (and some contemporary) memoirs; however, responding to student evaluations, newer material now ensures more diversity, with material written by women and people of color, and describes the difference that can make.

The Administrative Burden Of Medication Affordability Resources: An Environmental Scan With Implications For Health Informatics To Advance Health Equity., Marcy G Antonio, Jennylee Swallow, Rachel Richesson, Christine Carethers, Antoinette B Coe, Divya Jahagirdar, Yung-Yi Huang, Tammy Toscos, Mindy Flanagan, Tiffany C Veinot

Health Services and Informatics Research

OBJECTIVE: To characterize and demonstrate how to reduce the administrative burden experienced by patients when navigating medication affordability resources in the United States.

MATERIALS AND METHODS: Informed by administrative burden theory, we conducted an environmental scan of medication affordability resources for atrial fibrillation, and four common comorbidities (diabetes, heart failure, hypertension, and lipid disorder). We systematically searched for resources (eg, patient assistance programs, savings cards and nonprofit support) and extracted information about types, eligibility criteria, needed documentation, and application processes.

RESULTS: We identified 66 resources across 12 categories across the five conditions. The resources' varied eligibility criteria, application processes, and …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Who Reconstitutes The Chemotherapy? The Educational And Practice Needs Of Oncology Pharmacists In West Africa: A Call For Multidisciplinary Team Approach In Oncology Care., Runcie C.W. Chidebe, Ramatu M. Alabelewe, Krishna Prasad Sapkota, Darlingtina K. Esiaka, Candidus C. Nwakasi, Gloria C. Okwu, Jacinta Emejulu, Adamu A. Umar, Ndifreke Okwuegbunam, Funsho David, Toyosi Adepoju, Agha A. Agha, Ejike S. Ugwu, Simeon C. Aruah, Richard Mshelia, Rob Duncombe, Noel N. Wannang, Peace C. Babalola, R. Donald Harvey, Cindy O'Bryant, Folakemi T. Odedina

Behavioral Science Faculty Publications

PURPOSE: Oncology pharmacists (OPs) play a crucial role in cancer care, treatment, survivorship, and multidisciplinary teams (MDTs). OPs have specialized training in designing, administering, monitoring, and modifying oncology chemotherapy; managing adverse events; and evaluating clinical trials and investigational drugs. Yet, the state of OP has remained largely unknown in the clinical oncology workforce of the West African region. Therefore, this study aimed to understand who reconstitutes chemotherapy and to explain the OP educational and practice needs, challenges, and solutions in Nigeria.

MATERIALS AND METHODS: Using a concurrent embedded mixed method design, 35 OPs completed a questionnaire, and 12 others responded …

Call It When You See It: Major League Soccer Organization And Pediatric Hospital Team Up For Anti-Bullying Program., Ram Chettiar

Manuscripts, Articles, Book Chapters and Other Papers

Bullying remains a widespread social issue in the United States (US). Those who bully, are bullied, or witness bullying may experience negative emotional and physical consequences.1 To address the gap in accessible youth bullying interventions, Children's Mercy Kansas City partnered with Sporting Kansas City to develop Red Card KC, a bullying awareness program focusing on the impact of bystanders in bullying situations. The program is delivered to school and community partners through interactive assemblies educating youth on recognizing bullying, managing bullying situations, and standing up against bullying. Red Card KC has also partnered with schools to recognize and celebrate students …

Psychosocial Supports For The Physical And Mental Health Of Youth With Autism And Other Neurodevelopmental Disabilities., Melissa Campbell, Elizabeth Hastings, Paige Mcardle, Darren Olsen, Kathryn Benton, Cy Nadler

Manuscripts, Articles, Book Chapters and Other Papers

One in six youth has a neurodevelopmental disability (NDD), and autism diagnostic rates continue to rise. Before and after a diagnosis, families need trusted sources of guidance to navigate co-occurring medical and psychological conditions, and to manage unique stressors including transition to adulthood. However, medical professionals from all specialty areas struggle to identify resources to support the complex psychosocial and healthcare needs of these patients and their families. This primer on psychosocial supports for youth with autism will explore the major mental and physical health stressors faced by affected youth and families, and discuss opportunities for primary care and other …

Constantly Connected: What Healthcare Providers Need To Know About Vicarious Trauma In An Evolving Digitally Connected Global Community., Meghan Kanya, Patricia Davis, Gail Robertson

Manuscripts, Articles, Book Chapters and Other Papers

Easy access to streaming news and sensational headlines has transformed society's exposure to traumatic narratives. From personal stories on social media platforms to news articles about violence in communities, patients and their caregivers may not recognize their exposure as traumatic nor recognize their psychological sequalae as unhealthy. In addition, youth with trauma-related mental health symptoms are not consistently identified in pediatric primary care clinics. Due to the increase in proximity to traumatic stories, healthcare providers working with youth require additional skills designed to engage patients and families in conversations about exposure to violence via technology and symptoms of vicarious trauma. …

Screens Are Not The Enemy: Recommendations For Developing Healthy Digital Habits In Youth., Megan B. Bolch, Rachel Moore, Gail Robertson, Meredith J. Scafe, Libby Milkovich

Manuscripts, Articles, Book Chapters and Other Papers

With the rapid and ever-evolving growth of both digital media platforms and mental health concerns in youth, parents and practitioners are faced with the challenge of critically evaluating the effects of digital media use on youth development.1 Despite popular culture's narrow focus on the risks, research has established both positive and negative effects of youth digital media use.2,3 In contrast to interventions primarily focused on screen time limits, the goal of this article is to propose a framework for healthy digital habits rooted in a social-ecological model, called the Multisystemic Model of Digital Habits. This framework considers the intersection of …

Daily Physical Activity And Cardiorespiratory Fitness In Adults With Down Syndrome With And Without Congenital Heart Disease., Julianne G. Clina, David A. White, Joseph R. Sherman, Jessica C. Danon, Daniel Forsha, Brian C. Helsel, Richard A. Washburn, Joseph E. Donnelly, Lauren T. Ptomey

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Individuals with Down syndrome (DS) typically exhibit lower cardiorespiratory fitness and reduced moderate-to-vigorous physical activity (MVPA) compared to persons without disability. Approximately 50-55 % of individuals with DS have congenital heart disease (CHD), which is associated with cardiopulmonary deficiencies and reduced MVPA participation in non-DS populations. It is unknown if CHD related comorbidities compound with DS associated deficits in physical activity and fitness.

OBJECTIVE: To compare physical activity, cardiorespiratory fitness, and cardiovascular function, of persons with DS with and without CHD.

METHODS: Baseline data were used from a 12-month randomized controlled physical activity intervention of adults with DS. Participants …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

The Impact Of Household Dysfunction On Dating Violence Perpetration Among Adolescents In The United States: A Scoping Review, Sumaita Choudhury, Melissa F Peskin, Timothy J Walker, Emily T Hébert, Nivedhitha Parthasarathy, Kaitlyn L Zajack-Garcia, Lea Sacca, Christine M Markham

Faculty, Staff and Student Publications

Adverse childhood experiences, such as household dysfunction (HD), play a central role in how adolescents establish, experience, and navigate the challenges of relationship formation, maintenance, and dissolution. HD exposures have been independently associated with dating violence (DV) perpetration in both adolescents and adults. However, research examining the association between the concurrent effect of HD on DV perpetration, especially among adolescents remains scarce. Thus, we conducted a scoping review to accumulate and summarize existing research regarding the impact of HD on DV perpetration among adolescents aged 10 to 17 years in the United States. We used three electronic databases, Medline (Ovid), …

Dynamic Few-Shot Prompting For Clinical Note Section Classification Using Lightweight, Open-Source Large Language Models, Kurt Miller, Steven Bedrick, Qiuhao Lu, Andrew Wen, William Hersh, Kirk Roberts, Hongfang Liu

Faculty, Staff and Student Publications

Objective: Unlocking clinical information embedded in clinical notes has been hindered to a significant degree by domain-specific and context-sensitive language. Identification of note sections and structural document elements has been shown to improve information extraction and dependent downstream clinical natural language processing (NLP) tasks and applications. This study investigates the viability of a dynamic example selection prompting method to section classification using lightweight, open-source large language models (LLMs) as a practical solution for real-world healthcare clinical NLP systems.

Materials and methods: We develop a dynamic few-shot prompting approach to classifying sections where section samples are first embedded using a transformer-based …

Non-Invasive Tools For Analysis Of Plasma Membrane Protein Topology In Living Cells, Daria Savenkova, Leysan Bulatova, Vera Skripova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane protein topology studies offer guidance to membrane protein structure, folding, and function, serving as a credible scaffold for designing site-directed mutagenesis and biochemical experiments, helping to identify functionally significant extracellular and intracellular regions, modeling three-dimensional structures, and building reliable mechanistic models. Membrane protein structure as a function of given lipid composition and physiological state of the cell is best probed in whole intact cells. A described simple and advanced immunofluorescence protocol applied to the transmembrane orientation of extramembrane domains permits a topology analysis of plasma membrane proteins in their native state in living unperturbed eucaryotic cells. The accessibility of …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison B Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth F Sutton, Pamela M Simmons, George R Saade, Antonio Saad, Luis D Pacheco, Esther Park-Hwang, Antonina I Frolova, Ebony B Carter, Ai-Ris Y Collier, Daniel G Kiefer, Vincenzo Berghella, Rupsa C Boelig, Michal A Elovitz, Cynthia Gyamfi-Bannerman, Joseph R Biggio, Kara Rood, William A Grobman, Carrie Haverty, Morten Rasmussen

Faculty, Staff and Student Publications

Importance: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

Objective: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

Design, setting, and participants: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Incomplete Toxicity Reporting And Use Of Toxicity-Minimizing Language In Phase Iii Oncology Trials, Avital M Miller, Adina H Passy, Alexander D Sherry, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Gabrielle S Kupferman, Esther J Beck, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: This study aimed to determine complete toxicity reporting (CTR), and the use of subjective toxicity-minimizing language (TML) among phase III oncology trials.

Methods: Two-arm superiority-design phase III oncology trials published from 2002 to 2020 were reviewed for toxicity data. CTR was defined as reporting total adverse events (TAEs), total serious adverse events (SAEs), total deaths, and study therapy discontinuations because of toxicity. Guideline concordance was defined according to guidelines published in the BMJ (defined as reporting total SAEs, total deaths, and study therapy discontinuations because of toxicity). TML was defined as a set of terms that subjectively downplay the …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …