Digital Commons Network^™

Using Randomization To Compare Ai And Expert-Generated Formative Assessment Questions In Medical Education, Akshat Kumar, Katie Stinson, Litao Wang, Elizabeth Nugent, Yongsu Lee, Mark Hormann, Latanya Jones Love, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Background: AI-generated content is being used across the education spectrum and is beneficial for creating complex multiple-choice questions, such as those used in medical education. However, evaluating AI-generated content is challenging, and existing testing and evaluation methods are falling short. This study uses randomization to compare medical students' performance on and subjective evaluation of AI versus expert-generated questions. We hypothesized that there would be no difference in student performance or subjective evaluation of AI vs expert-generated questions.

Methods: We designed a single-center, randomized study where medical student participants received either one AI- or expert-generated question per day over four weeks. …

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Geoffrey A Preidis, Hania Szajewska, Marla Cunningham, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Impact Of School Nurse Education On Factors Influencing Hpv Vaccine Communication With Parents, Jihye Choi, Efrat K Gabay, Jeanette Deason, Elizabeth Baumler, Diane Santa Maria, Daisy Mullassery, Lara S Savas, Erika Thompson, Sanghamitra M Misra, Paula M Cuccaro

Faculty, Staff and Student Publications

Human papillomavirus (HPV) can cause six cancer types but can be prevented with timely vaccination in early adolescence. However, despite the wide availability of the HPV vaccine, uptake remains suboptimal among US adolescents. School nurses are invaluable resources to students and their families regarding adolescent immunization needs. As part of the All for Them vaccination program, we assessed the impact of the continued nurse education (CNE) intervention on school nurses’ HPV vaccine communication with parents. Seventy-two school nurses and nurse administrators in Texas participated in the study. Using a single-arm study design, we measured participants’ potential barriers to and self-efficacy …

Emotional Urgency And Lack Of Perseverance Are Linked To Anxiety Sensitivity And Improve During Early Recovery From Opioid Use Disorder., Breanna A. Mcnaughton-Long, Abigail J. Pleiman, Carmen Buchfink, Chrysantha B. Davis, Rayus Kuplicki, Martin P. Paulus, Hung-Wen Yeh, Maëlle C M Gueguen, Jennifer L. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

Few studies have identified how facets of impulsivity relate to recovery in opioid use disorder (OUD). Treatment-enrolled individuals with OUD (n = 167) and healthy controls (CTL; n = 46) completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale along with demographic and clinical measures at visit 1. Over the next three months, abstinence and return to use were documented for participants with OUD (via self-report, alcohol breathalyzer, urine drug screen, and secondary contact communication). Participants with OUD who returned to use (n = 59) did not complete further study visits, whereas those who remained abstinent …

Ceftaroline Pharmacokinetics On Ecmo, A Pediatric Case Report., Kathryn Pavia, Ashton Bellamy, Alaina Burns, Allison Scott, Ethan A. Poweleit

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In-vitro studies suggest that patients on extracorporeal membrane oxygenation (ECMO) may struggle to achieve therapeutic ceftaroline exposure to treat infections due to antibiotic sequestration within the ECMO oxygenator; however, there are no published data regarding ceftaroline concentrations from patients supported by ECMO.

PATIENT PRESENTATION: Here we present an analysis of ceftaroline pharmacokinetics in a 5-y-old patient supported on ECMO due to influenza-associated necrotizing pneumonia.

RESULTS: A total of nine concentrations were analyzed, including three concentrations prior to cannulation and six on ECMO. ECMO cannulation was associated with a relatively small change in the volume of distribution (0.17 L/kg to …

Early Prediction Of The Breast Cancer Response To Neoadjuvant Chemotherapy Based On Intratumoral Interstitial Fluid Pressure Using 3-D Subharmonic-Aided Pressure Estimation, Sung In Choi, Basak Dogan, Corinne E. Wessner, Jessica H. Porembka, Priscilla Machado, B. Bersu Ozcan, Nisha Unni, Maysa Abu-Khalaf, Kenneth Hoyt, Flemming Forsberg, Kibo Nam

Department of Radiology Faculty Papers

Elevated intratumoral interstitial fluid pressure (IFP) may negatively impact the efficacy of neoadjuvant chemotherapy (NAC). This study aimed to predict the breast cancer response to NAC based on intratumoral IFP using 3D contrast-enhanced ultrasound (CEUS) with subharmonic-aided pressure estimation (SHAPE). This prospective study enrolled breast cancer patients undergoing NAC from two clinical sites. 3D CEUS was performed at 0%, 10%, and 30% of NAC completion using a GE Logiq E9 with Definity. The pressure gradients between the tumor and adjacent normal tissue were estimated by SHAPE, utilizing the inverse linear relationship between the ultrasound contrast agent’s subharmonic signal amplitude and …

Streamlining Diagnosis Of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria., Jeremy J. Pomeroy, Jesse Richards, Brooke Sweeney, Seema Kumar, Katie E. Queen, Joshua Zaritsky, Carl H. Cramer, Elias I. Traboulsi, Brittni A. Scruggs, Erica E. Davis, Ekaterina Keifer, Emma Mcgibbon, Timothy Ogden, Bendert De Graaf, Tonia Hymers, Elizabeth Forsythe, Philip Beales

Manuscripts, Articles, Book Chapters and Other Papers

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals <  2 years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting ≥ 1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Individual Host Variation In Single-Cell Responses To Enteroaggregative Escherichia Coli Infection Modeled With Human Colon Organoids, Ling Qiu, Tajhal D Patel, Hannah E Jones, Cristian Coarfa, Anthony W Maresso

Faculty, Staff and Students Publications

Enteroaggregative Escherichia coli (EAEC) is a leading cause of diarrhea worldwide. Interestingly, EAEC disease outcomes vary dramatically among infected individuals, ranging from asymptomatic colonization to acute and chronic diarrhea. While previous research has focused on EAEC virulence factors, emerging evidence suggests that host genetic and cellular background may be equally important in determining disease susceptibility. To understand host-driven disease heterogeneity, we performed single-cell RNA sequencing on human colon organoids (HCOs) derived from three healthy adult donors following EAEC 042 infection. Surprisingly, despite comparable EAEC adherence across donors, we observed striking donor-specific responses to infection at multiple levels. A total of …

Strengthening Health System-Community Partnerships To Address Pediatric Social Needs: A Qualitative Study, Joy Friedman, Melissa A. Alderfer, Kelsey Higgins, Aaron Carpenter, Jennifer Sciolla, Sarah E. Wawrzynski

Department of Pediatrics Faculty Papers

IntroductionStructural and social conditions influence pediatric health outcomes. Successful implementation of social needs screening and referral programs depends on community-based organizations (CBOs) to provide resources that address health-related social needs (HRSN). We explored current practices and perspectives of health care workers and CBO representatives on improving health system-CBO partnerships.MethodsParticipants were purposively recruited from a variety of health care settings involved in HRSN screening and CBOs delivering resources in the community. Participants completed semi-structured interviews. Qualitative thematic analysis was used to summarize data.ResultsTen key informants participated (six health care workers and four CBO representatives). Four themes were identified: 1) mismatches in …

Blinatumomab Care Delivery For Pediatric B-Cell Acute Lymphoblastic Leukemia, Daniel Zheng, Katelyn Oranges, Subhash Ramakrishnan, Lingyun Ji, Melissa Beauchemin, Sarah Alexander, Allison Leahy, Kira Bona, Emi Caywood, Sharon Castellino, Sumit Gupta, Douglas Hawkins, Olga Militano, Kathleen Montgomery, Haley Newman, Rachel Rau, Susan Rheingold, Joanna Robles, Michael Roth, David Teachey, Sarah Vargas, Sue Zupanec, Susan Parsons

Department of Pediatrics Faculty Papers

IMPORTANCE: Blinatumomab, a novel immunotherapy administered as a 28-day continuous infusion, has fundamentally shifted the treatment paradigm for pediatric B-cell acute lymphoblastic leukemia (B-ALL) and is now considered a component of standard therapy for the most common childhood cancer. However, the care delivery challenges in transitioning from an experimental agent on a clinical trial to widespread clinical implementation are unknown.

OBJECTIVE: To characterize the clinical landscape of pediatric blinatumomab care-delivery practice and challenges in the US from the perspective of treating centers.

DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted from February to March 2025 among US member institutions …

Diversity Among Academic Orthopaedic Surgery Sports Medicine Faculty Across Us Residency Programs, Terence L. Thomas, Alexander Zavitsanos, Claude Regis, John Czarnicki, Harrison S. Fellheimer, Gabriel I. Onor, William Justice, Jalen Broome, Damon V. Briggs, Edward S. Chang, Meghan Bishop, Christopher C. Dodson

Rothman Institute Papers

BACKGROUND: Despite growing attention to workforce diversity in orthopaedic surgery, limited data exist describing the demographic composition of academic sports medicine faculty. This study examines the diversity of sports medicine fellowship-trained orthopaedic surgery faculty across US orthopaedic surgery residency training programs.

METHODS: A cross-sectional analysis of all ACGME-accredited orthopaedic surgery sports medicine faculty was conducted. Faculty data included sex, race, level of professorship, residency attended, year of residency graduation, and h-index. Underrepresented in Orthopaedics (URiO) was defined as non-White and non-Asian by race and all women. Descriptive statistics were performed.

RESULTS: A total of 812 sports medicine-fellowship trained faculty were …

Androgens Mediate Sexual Dimorphism In Pilarowski-Bjornsson Syndrome., Kimberley Jade Anderson, Eirny Tholl Thorolfsdottir, Ilana M. Nodelman, Sara Tholl Halldorsdottir, Stefania Benonisdottir, Malak A. Alghamdi, Naif A M Almontashiri, Brenda J. Barry, Matthias Begemann, Jacquelyn F. Britton, Sarah Burke, Benjamin Cogne, Ana S A Cohen, Carles De Diego Boguñá, Evan E. Eichler, Elizabeth C. Engle, Jill A. Fahrner, Laurence Faivre, Mélanie Fradin, Nico Fuhrmann, Christine W. Gao, Gunjan Garg, Dagmar Grečmalová, Mina Grippa, Jacqueline R. Harris, Kendra Hoekzema, Tova Hershkovitz, Sydney Hubbard, Katrien Janssens, Julie A. Jurgens, Stanislav Kmoch, Cordula Knopp, Meral Aktas Koptagel, Farah A. Ladha, Pablo Lapunzina, Tobias Lindau, Marije Meuwissen, Andreina Minicucci, Emily Neuhaus, Mathilde Nizon, Lenka Nosková, Kristen Park, Chirag Patel, Rolph Pfundt, Pankaj Prasun, Nils Rahner, Nathaniel H. Robin, Carey Ronspies, Jasmin Roohi, Jill Rosenfeld, Margarita Saenz, Carol J. Saunders, Zornitza Stark, Isabelle Thiffault, Sarah Thull, Danita Velasco, Clara Velmans, Jolijn Verseput, Antonio Vitobello, Tianyun Wang, Karin Weiss, Ingrid M. Wentzensen, Genay Pilarowski, Thor Eysteinsson, Madelyn Gillentine, Kári Stefánsson, Agnar Helgason, Gregory D. Bowman, Hans Tomas Bjornsson

Manuscripts, Articles, Book Chapters and Other Papers

Sex-specific penetrance in autosomal-dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived Chd1 missense variant (Chd1^R616Q/+) displays female-restricted phenotypes, including growth deficiency, anxiety, and hypotonia. Orchiectomy unmasks a growth-deficiency phenotype in male Chd1^R616Q/+ mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants …

Current State And Needs Of Clinical Laboratories In Selected Countries In Africa, Merih Tesfazghi, Anne E Tebo, Roa Harb, Anthony O Okorodudu, Lee Schroeder, Jeannette Guarner, Christine Bales, Jack Ladenson, Allison Targowski, Kerry Cosby, Olajumoke Oladipo

2020-Current year OA Pubs

The Africa Working Group, under the auspices of the Global Laboratory Quality Initiative of the Association for Diagnostics & Laboratory Medicine (ADLM), conducted several educational workshops in Africa to promote laboratory quality in the region. The challenges faced in maintaining quality in clinical laboratories in low-resource countries may differ from region to region and country to country. To better understand current gaps and inform our engagement with partners in Africa, a needs assessment survey was distributed to 1427 ADLM members in Africa and further disseminated through local partners, resulting in 121 responses from participants across 8 countries in the region. …

Non-Vigorous Physical Activity Associated With Reduced Hospitalization Risk With Or Without Diabetes Or Peripheral Artery Disease: Study Of Latinos., Sarah K. Alver, Carmen C. Cuthbertson, Kelly R. Evenson, Jennifer A. Schrack, Daniela Sotres-Alvarez, Natasha Z. Anita, Yasmin Mossavar-Rahmani, Linda C. Gallo, Jordan A. Carlson, Matthew Allison, Martha L. Daviglus, Olga Garcia-Bedoya, Christina Cordero, Xiaonan Xue, Jianwen Cai, Kunihiro Matsushita, Robert C. Kaplan

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study assessed whether greater physical activity (PA) and lesser sedentary behavior (SB) reduce hospitalization risk equally among those with and without prediabetes, diabetes, or peripheral artery disease (PAD).

METHODS: We studied PA, SB and hospitalizations in 12,734 adults from the Hispanic Community Health Study/Study of Latinos, who were 52.2% female with mean (standard deviation) age 41.1 (14.9) yr at baseline. Participants reported 10,025 nonpregnancy-related hospitalizations (excluding emergency room only) over 13 yr. We modeled the association between accelerometer-measured activity (SB; light intensity physical activity [LPA]; moderate physical activity [MPA]; vigorous physical activity [VPA]) and hospitalization, using Andersen-Gill proportional …

Measuring Quality Of Life In Advanced Chronic Liver Disease With Fact-Hep: Findings From The Pal Liver Trial, Manisha Verma, Binu John, Don Rockey, Sid Barritt, Victor Navarro, Linda Shaw, Andrzej Kosinski, Elliot Tapper, Archita Desai

Einstein Health Papers

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly incorporated into hepatology research, yet few have been rigorously evaluated, particularly among patients with decompensated cirrhosis. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) captures multidimensional liver disease-specific burden, while the disease-agnostic PROMIS-29 assesses physical and mental health broadly. We evaluated the performance of FACT-Hep and its relationship to PROMIS-29 among participants with cirrhosis or hepatocellular carcinoma (HCC) enrolled in a prospective multicenter clinical trial.

METHODS: Baseline data were analyzed from 935 participants enrolled in the PAL LIVER trial. This study enrolled patients with Child-Turcotte-Pugh (CTP) B/C cirrhosis and/or with HCC. Health-related quality of …

Best Practices For Supporting Occupational Therapy Students With Disabilities During Clinical Education: Results From A Three-Round Delphi Study, Courtney Gohean, Katie Mclaughlin, Aster Harrison

Department of Occupational Therapy Faculty Papers

INTRODUCTION: Disabled occupational therapy students face systemic barriers in clinical education. Although legal mandates require reasonable accommodations, implementation is often inconsistent, and few standardized guidelines exist for fieldwork education. This study is aimed at establishing best practices for supporting occupational therapy and occupational therapy assistant students with disabilities during fieldwork.

MATERIALS AND METHODS: A three-round Delphi study was conducted with a panel of 30 experts, including disabled occupational therapy students, disabled occupational therapy practitioners, academic fieldwork coordinators (AFWCs), fieldwork educators (FWEs), disability services staff, and researchers. In Round 1, participants answered open-ended questions about challenges, accommodations, and environmental supports. Responses …

How Conditions Within Immigration Removal Centres In The United Kingdom Affect The Mental Wellbeing Of Detainees: A Scoping Review, Niamh Gallagher, Tristan Price, Matthew Griggs

Peninsula Medical School

BackgroundImmigration Removal Centres (IRCs) are used to detain people for immigration control by the UK government. This scoping review aims to examine the experiences of detainees within UK IRCs, specifically how conditions within them, including the regime, affect their mental wellbeing.MethodsThe Joanna Briggs Institute guideline for scoping reviews was followed. Six bibliographic databases and additional grey literature sources were searched for quantitative and qualitative evidence. Descriptive analyses and quality assessments were conducted.ResultsFifteen research studies and nine pieces of grey literature were included, comprising a total of 1353 participants and 11 IRCs. The majority of data was qualitative in methodology and …

The American Society Of Extracorporeal Technology Standards And Guidelines For Pediatric And Congenital Perfusion Practice: 2025 Update☆., Molly Elisabeth Oldeen, Carrie Whittaker Striker, Ronald Angona, Dafne Andrea Chianella, Chelsea Capone, Ashley B Walczak, Thomas Klein

Heart and Vascular Articles

Background: In 2019, the American Society of ExtraCorporeal Technology (AmSECT) approved the inaugural Standards and Guidelines for Pediatric and Congenital Perfusion Practice. These standards and guidelines were created with the intent of periodic revision to ensure continued alignment with evolving best practices. In 2023, an AmSECT subcommittee initiated this review in consideration of current literature and contemporary clinical practices.

Methods: The subcommittee, consisting of pediatric and congenital perfusionists, conducted a systematic literature review assessing each standard and guideline to determine if current evidence supports elevation of guidelines to standards, incorporation of new guidelines or standards, or whether existing standards and …

Pda (Privacy-Preserving Distributed Algorithms) In Action: Ten Principles For High-Quality Multi-Site Clinical Evidence Generation, Yong Chen, Chongliang Luo, Et Al.

2020-Current year OA Pubs

BACKGROUND: Distributed Research Networks (DRNs) offer significant opportunities for collaborative multi-site research and have significantly advanced healthcare research based on clinical observational data. However, generating high-quality real-world evidence using fit-for-use data from multi-site studies faces important challenges, including biases associated with various types of heterogeneity within and across sites and data sharing difficulties. Over the last 10 years, Privacy-Preserving Distributed Algorithms (PDA) have been developed and utilized in numerous national and international real-world studies spanning diverse domains, from comparative effectiveness research, target trial emulation, to healthcare delivery, policy evaluation, and system performance assessment. Despite these advances, there remains a lack …

Towards Human-Centered Digital Health Interventions, Kristin M Kostick-Quenet, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

This article discusses the potential of digital health interventions (DHIs) in mental health care, emphasizing the importance of designing them to foster genuine humanistic care. It highlights current challenges in measuring engagement and outcomes, advocating for integrating human-centered endpoints such as dignity, autonomy, and therapeutic alliance into evaluation frameworks. The authors call for mechanistic research to identify effective engagement strategies and context-specific implementation approaches. Ultimately, successful DHIs should demonstrate both clinical efficacy and the preservation of humane, person-centered care, ensuring ethical and meaningful mental health support through technology.

Perioperative Depression And Anxiety Care In Older Patients: A Randomized Clinical Trial, Joanna Abraham, Katherine J Holzer, Simon Haroutounian, Bethany Pennington, Ana Baumann, Ryan Calfee, Theresa Cordner, Kenneth E Freedland, Thomas Kannampallil, Benjamin Kozower, Emily Lenard, J Philip Miller, Mary Politi, Michael Yingling, Michael S Avidan, Eric J Lenze

2020-Current year OA Pubs

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking.

OBJECTIVE: To evaluate a perioperative intervention to optimize mental health.

DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety …

Responding To Medetomidine In Philadelphia: Narrative Summary Of The Public Health Response To A New Psychoactive Substance, Tareva Warrick-Stone, Serge-Emile Simpson, Phil Durney, Dennis Goodstein, Catherine Abrams, Raymond Bobb, Kory London, Daniel Teixeira Da Silva

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Despite the emergence of medetomidine as the dominant adulterant in Philadelphia's illicit opioid supply, coordinated public health responses are limited or non-existent in the literature. Thus, we summarize a recent Summit in Philadelphia of outpatient and inpatient service providers who specialize in the care of persons who use drugs to discuss medetomidine response readiness and building ongoing community readiness for potential destabilizing drug supply changes.

PURPOSE: Describe a public health intervention that distributed information about practices across health care settings and mobilized key informants to identify and address barriers to treatment.

METHODS: Descriptive summary of the in-person Summit organized …

Crosstalk Between Upr And Mitochondria: The Triad Of Er-Mitochondria Contacts, Ca²⁺, And Ros, Ester Zito, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum (ER) stress is triggered by several cellular perturbations causing protein misfolding, and activates the unfolded protein response (UPR), an initially adaptive signaling network that aims to restore ER and cellular homeostasis. Growing evidence indicates that UPR signaling extends beyond ER proteostasis, influencing mitochondrial function and bioenergetics through ER-mitochondria contact sites (ERMCs). The CHOP-ERO1A-IP3R axis has a primary role in recruiting mitochondria to adaptive UPR. However, its sustained activation renders UPR signaling maladaptive, leading to mitochondrial dysfunction through both outer mitochondrial membrane permeabilization (OMMP) and mitochondrial permeability transition pore (mPTP) opening, ultimately contributing to irreversible cell injury and disease …

Endothelin Receptor Antagonists In Resistant Hypertension And Proteinuric Kidney Disease: Receptor Strategy And Volume Management, Corey Keith Goldman, Jesse M. Goldman

Division of Nephrology Faculty Papers

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in …

Heritable Transgenic Schistosomes As A Living Platform For Sars-Cov-2 Neutralizing Antibody Secretion, Wannaporn Ittiprasert, Bruce A Rosa, Sergej Djuranovic, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Integrative Rna-Seq Analysis Reveals Stress Type-Dependent Lncrna-Centered Co-Expression Networks Across Human Cellular Stress Contexts, Christina Anastasiadi, Aggeliki Kasapi, Ioannis Sentementes, Vasileios Gouzouasis, Margaritis Tsifintaris, Antonis Giannakakis

Computational Medicine Center Faculty Papers

Long non-coding RNAs (lncRNAs) are emerging as important regulators of cellular adaptation to environmental and molecular stress, but the extent to which their responses remain reproducible and stress-type-dependent across human stress conditions remains unclear. Here, we performed an integrative transcriptomic meta-analysis of human stress-response datasets from ASTRA and GEO, focusing on normal, non-cancerous, wild-type human cell lines exposed to oxidative stress (H2O2), hypoxia, heat stress, or UV-induced DNA damage. Gene Ontology (GO) enrichment analysis of differentially expressed (DE) protein-coding mRNAs confirmed that the resulting stress-stratified comparison captured biologically coherent transcriptional programmes to oxidative stress signaling, hypoxic and metabolic adaptation, heat-induced …

Formative Work To Guide Implementation Of An Evidence-Based Breast And Cervical Cancer Prevention And Early Detection Behavioral Health Program In Clinics: Qualitative Study Guided By The Consolidated Framework For Implementation Research, Marlyn A Allicock, Crystal Costa, Ashley Hedrick Mckenzie, Preena Loomba, Roshanda S Chenier, Ross Shegog, Angelita Alaniz, Maria E Fernandez, Lara S Savas

Faculty, Staff and Student Publications

Background: Salud en Mis Manos (SEMM) is a community health worker-delivered evidence-based intervention shown to increase breast and cervical cancer screening in medically underserved Latinas. Despite SEMM's success in community-based settings, clinic-based implementation is limited.

Objective: This study aimed to identify factors influencing the implementation of SEMM in clinic settings using the Consolidated Framework for Implementation Research (CFIR) to inform and refine implementation strategy development.

Methods: We developed theory-informed (eg, CFIR, Social Cognitive Theory, and Readiness) interview guides to elicit barriers and facilitators of SEMM clinic implementation. We conducted 12 semistructured interviews with clinic leaders, outreach coordinators, and community health …

Digital Markers For Passive Remote Monitoring Of Bipolar Disorder: Systematic Review, Thomas P Kutcher, Isha Chakraborty, Kristin Kostick-Quenet, Akane Sano, Nidal Moukaddam, Jeffrey A Herron, Wayne K Goodman, Sameer A Sheth, Ashutosh Sabharwal, Nicole R Provenza

Duncan NRI Faculty and Staff Publications

Background: Bipolar disorder (BD) features episodic shifts among mania, hypomania, depression, mixed states, and euthymia. Timely detection of mood transitions is difficult due to infrequent clinical touchpoints. Digital health technologies, including wearables and smartphones, offer a unique opportunity to passively and continuously monitor behavior and physiology that could reflect underlying mood dynamics in real-world settings.

Objective: This study aimed to systematically review passively collected digital markers for BD mood states, characterize devices/modalities and analytic approaches, appraise risk of bias, and identify design gaps and priorities for clinical translation.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

Th17 Effector Cytokines Induce Shared And Distinct Microglial And Endothelial Cell Responses In A Mouse Model For Post-Streptococcal Encephalitis, Charlotte Wayne, Uğur Akcan, Travis Faust, Violeta Durán-Laforet, Danny Jamoul, Luca Bremner, Nicole Ampatey, Büşra Akcan, Sarah Ho, Bogoljub Ciric, Shannon Delaney, Wendy Vargas, Susan Swedo, Vilas Menon, Dorothy Schafer, Tyler Cutforth, Dritan Agalliu

Department of Neurology Faculty Papers

Group A Streptococcus (GAS) infections cause neuropsychiatric complications in children, but the mechanisms linking peripheral infection to brain dysfunction remain unclear. Using mouse genetics, single-cell RNA sequencing, and spatial transcriptomics, we show that GAS infections induce inflammatory transcriptional programs in microglia and brain endothelial cells (BECs), accompanied by loss of blood-brain barrier (BBB) gene expression in female mice. Spatial transcriptomic analyses reveal that GAS-responsive microglia localize near infiltrating CD4+ T cells. Several microglial chemokines induced in mice are elevated in sera from affected patients. Deletion of GM-CSF in CD4⁺ T cells partially reduces microglial chemokine gene expression, without restoring BBB …