Medicine and Health Sciences Commons^™

Letter From The Editor, Sarah Nechuta

Michigan Journal of Public Health

No abstract provided.

Endovascular Repair Of Graft-To-Graft Ascending Aortic Pseudoaneurysm, Joshua R. Chen, Vishal N. Shah, Mitchell Hirsch, Thomas Jefferson University, Gaurang Joshi, Konstadinos A. Plestis, Babak Abai

Department of Surgery Faculty Papers

No abstract provided.

Feasibility Of A Low-Intensity Intervention To Influence Antibiotic Prescribing Rates Use In Outpatient Settings: A Cluster Randomized Controlled Clinical Trial, Brigid M. Wilson, Sunah Song, Robin L.P. Jump, Federico Perez

Faculty Scholarship

Background. Primary care providers (PCPs) may modify their antibiotic prescription practices if aware of their potentially damaging impact. Methods. We conducted a cluster randomized controlled trial at 12 Veterans Affairs community-based outpatient clinics. PCPs at clinics randomized to the intervention group received quarterly antibiotic use reports with feedback about antibiotics prescribed for acute respiratory infections and adverse event letters alerting about Clostridioides difficile infection or antibiotic-resistant gram-negative bacteria among their patients. The main outcome, antibiotic prescriptions in primary care visits, was compared in the preintervention (April–September 2020), intervention (October 2020 to September 2021), and postintervention periods (September 2021 to September …

Unilateral Hemicraniectomy With Titanium Cranioplasty For The Treatment Of High Intracranial Pressure In A Pediatric Patient With Camurati-Engelmann Disease: Illustrative Case, Roboan Guillen-Arguello, Nicholas Sader, J. Gordon Mccomb

School of Medicine Faculty Publications

BACKGROUND Camurati-Engelmann disease (CED) is an extremely rare autosomal dominant genetic disorder that can cause increased intracranial pressure (ICP) secondary to cranial hyperostosis, which decreases intracranial volume. Surgical procedures to reduce ICP in medically refractory cases include intracranial volume expansion and ventriculoperitoneal shunting. OBSERVATIONS The authors present the case of a pediatric patient with CED and medically refractory increased ICP who underwent unilateral hemicraniectomy with titanium cranioplasty, resulting in a complete long-term resolution of symptoms. LESSONS Unilateral hemicraniectomy with titanium cranioplasty is a feasible surgical treatment for CED in pediatric patients with medically refractory increased ICP and papilledema.

Innovations In Genicular Outcomes Registry (Igor): Protocol For A Real-World Registry Study Of Treatments For Knee Osteoarthritis, Vinod Dasa, William Mihalko, Adam Rivadeneyra, Joshua Urban, Andrew Wickline, David Rogenmoser, Andrew Concoff, Andrew Spitzer, Michael A. Mont

School of Medicine Faculty Publications

BACKGROUND: Osteoarthritis (OA) is the leading cause of disability among US adults and most commonly affects the knee. Guidelines for knee OA treatment include behavioral, nonpharmacological, pharmacological, and surgical interventions. While emerging knee OA treatments show promise for pain control, data gaps remain regarding the efficacy, safety, comparative effectiveness, and real-world value of treatments. OBJECTIVES: The Innovations in Genicular Outcomes Registry (IGOR) is prospectively collecting real-world data to assess clinical effectiveness, safety, health-related quality of life, and healthcare resource utilization of knee OA treatments. DESIGN: The IGOR is a prospective, observational, longitudinal, multicenter registry (NCT05495334) examining knee OA pain treatment …

Patient-Reported Functional Outcomes And Treatment-Related Regret In Hispanic And Spanish-Speaking Men Following Prostate Cancer Treatment, Andrea A. Lopez, Bashir Al Awamlh, Li-Ching Huang, Zhiguo Zhao, Tatsuki Koyama, Karen E. Hoffman, Christopher J. Wallis, Kerri Cavanaugh, Ruchika Talwar, Alicia K. Morgans, Michael Goodman, Ann S. Hamilton, Xiao-Cheng Wu, Jie Li, Brock B. O'Neil, David F. Penson, Daniel A. Barocas

School of Public Health Faculty Publications

OBJECTIVES: Compare functional outcomes and treatment-related regret over 10 years in Spanish- and English-speaking Hispanic men compared to non-Hispanic men following treatment of localized prostate cancer. METHODS AND MATERIALS: Data from a prospective cohort study of men with localized prostate cancer treated with active surveillance, radical prostatectomy or radiotherapy were used to examine the effect of survey language (Spanish speaking vs. English speaking) and ethnicity (Hispanic vs. non-Hispanic) on functional outcomes and treatment-related regret over 10 years. Outcomes were measured using validated questionaries adjusting for baseline patient and disease characteristics. RESULTS: A total of 770 men were included, 12% were …

Effectiveness Of An Improved Leprosy Lakar Training On Knowledge And Skills Among Healthcare Workers In Primary Healthcare In Pahang Malaysia., Nuraihan Zafirah Zainal Abidin

Student Works (2020-2029)

Leprosy, a neglected chronic tropical disease caused by Mycobacterium leprae, poses significant health challenges due to its potential for irreversible disabilities and disfigurement. Adequate leprosy training for healthcare workers (HCWs) is crucial for early detection and prompt treatment, thereby preventing complications and reducing transmission risks. This study aimed to revise and evaluate the effectiveness of leprosy LaKAR* training on knowledge and skills of leprosy among HCWs in primary healthcare in Pahang, Malaysia. The study employed a sequential exploratory, mixed-method design consisting of two phases. Phase 1a was a qualitative study identifying gaps in current LaKAR training among HCWs at …

Correlation Of Genogroup I, Genotype 1 (Gi.1) Norovirus Neutralizing Antibody Levels With Gi.1 Histo-Blood Group Antigen-Blocking Antibody Levels, Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Background: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.

Methods: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.

Results: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.

Conclusions: Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …

Pediatric Flecainide Pharmacogenomics: A Roadmap To Delivering Precision-Based Care To Pediatrics Arrhythmias., Ronald Palmen, Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Flecainide acetate is a Class 1c anti-arrhythmic with a potent sodium voltage gated channel blockade which is utilized for the second-line treatment of tachyarrhythmias in children and adults. Given its narrow therapeutic index, the individualization of drug therapy is of utmost importance for clinicians. Despite efforts to improve anti-arrhythmic drug therapy, there remain knowledge gaps regarding the impact of variation in the genes relevant to flecainide's disposition and response. This variability is compounded in developing children whose drug disposition and response pathways may remain immature. The purpose of this comprehensive review is to outline flecainide's disposition and response pathways while …

Letter From The President, Suzanne Keep

Michigan Journal of Public Health

No abstract provided.

Reducing Detroit’S Heart Disease Risk: The Role Of Social Determinants Of Health And Health Behaviors, Caress A. Dean, Rebecca Milan, Maidah Raja, Swathi Radhakrishnan

Michigan Journal of Public Health

Introduction: The age-adjusted death rates related to heart disease have been increasing in Detroit, Michigan. Recognizing public health professionals' role in promoting and protecting community health, this study examined the relationship between cardiovascular health and health beliefs, behavior tracking, and social determinants of health among Detroit residents.

Methods: This cross-sectional study was guided by the World Health Organization's conceptual framework of social determinants of health, which classifies social determinants into structural (e.g., socioeconomic factors) and intermediary (e.g., behavioral factors) categories. From May 2019 to August 2021, 394 residents of Detroit were recruited to complete a survey about their …

Predictors Of Low Birthweight Using Data From Electronic Medical Records In Flint, Michigan, 2013 To 2016, Rie Suzuki, Neida Monroy-Sechague

Michigan Journal of Public Health

Introduction: Infant mortality continues to be a major health problem in Michigan, with low birthweight (LBW) being a leading cause. Between 2020 and 2022, Black infants were nearly twice as likely to be LBW compared to White infants. The purpose of this study was to use electronic medical records (EMR) data to assess predictors of LBW and determine whether race influenced this relationship using a unique data source of EMR in Flint, Michigan (MI).

Methods: A retrospective study from 2013 to 2016 was conducted at the Health Resources and Services Administration local health center in Flint, MI. Demographics, birth …

Enhancing Communication And Swallowing Skills In Children With Cri Du Chat Syndrome: A Comprehensive Speech Therapy Guide, Soultana Papadopoulou, Areti Anagnostopoulou, Dimitra V. Katsarou, Kalliopi Megari, Efthymia Efthymiou, Alexandros Argyriadis, Georgios Kougioumtzis, Maria Theodoratou, Maria Sofologi, Agathi Argyriadi, Efterpi Pavlidou, Eugenia I. Toki

All Works

Background: A specific deletion on the short arm of chromosome 5 (5p) is the hallmark of the rare genetic syndrome called Cri du Chat Syndrome (CdCS). It causes severe difficulty with swallowing, speech, motor skills, and cognitive deficiencies. These arise from characteristic laryngeal abnormalities and oral–motor dysfunctions. Objective: This study aims to investigate the effectiveness of speech and language intervention in addressing the multifaceted challenges of CdCS, including speech and language impairments, feeding difficulties, and social communication deficits. Methods: A narrative review was conducted to synthesize existing studies from the last 35 years on therapeutic interventions for individuals with CdCS. …

Identification Of An Early Subset Of Cerebellar Nuclei Neurons In Mice, Maryam Rahimi-Balaei, Shayan Amiri, Thomas Lamonerie, Sih-Rong Wu, Huda Y Zoghbi, G Giacomo Consalez, Daniel Goldowitz, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium. Embryos were collected at early stages of development and processed for immunohistochemistry (IHC), western blotting, in situ hybridization (ISH), embryonic culture, DiI labeling, and flow cytometry analysis (FCM). Our findings indicate that …

A Statistical Approach For Systematic Identification Of Transition Cells From Scrna-Seq Data, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li, Ken Chen

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

Changes In Reproductive Health Information-Seeking Behaviors After The Dobbs Decision: Systematic Search Of The Wikimedia Database, Mackenzie Lemieux, Cyrus Zhou, Caroline Cary, Jeannie Kelly

2020-Current year OA Pubs

BACKGROUND: After the US Supreme Court overturned Roe v. Wade, confusion followed regarding the legality of abortion in different states across the country. Recent studies found increased Google searches for abortion-related terms in restricted states after the Dobbsv. Jackson Women's Health Organization decision was leaked. As patients and providers use Wikipedia (Wikimedia Foundation) as a predominant medical information source, we hypothesized that changes in reproductive health information-seeking behavior could be better understood by examining Wikipedia article traffic.

OBJECTIVE: This study aimed to examine trends in Wikipedia usage for abortion and contraception information before and after the Dobbs decision.

METHODS: Page …

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation For B-Lineage Acute Lymphoblastic Leukemia, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li, Ken Chen

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

Detection Of Kmt2a Partial Tandem Duplication By Optical Genome Mapping In Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, And Patient Outcomes, Qing Wei, Shimin Hu, Jie Xu, Sanam Loghavi, Naval Daver, Gokce A Toruner, Wei Wang, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients …

Cutaneous Nodules Secondary To Mycobacterium Avium Complex In A Patient With Human Immunodeficiency Virus, Jay Patel, Shannon Sayyadioskoie, Hanna Siatecka, Theodore Rosen

Faculty, Staff and Students Publications

We present a patient with human immunodeficiency virus who developed multiple painful lesions that previously in the past had speciated as Cryptococcus neoformans cutaneously, and in the lung. Despite induction therapy for presumed re-infection, the patient did not improve so a biopsy was performed and this was speciated as Mycobacterium avium complex, with final diagnosis being disseminated Mycobacterium avium complex. This case highlights the importance of considering a broad differential diagnosis for any new lesions regardless of prior culture data.

Pharmacologic Blockade Of A Pioneer Transcription Factor, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

Cancers frequently co-opt lineage-specific transcription factors (TF) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new article by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute myeloid leukemia. Immobilization and sequencing of genomic DNA targeted by these compounds revealed that these inhibitors alter the genomic binding patterns of PU.1. The authors report that their strategy constrains the genomic binding preferences of PU.1, leading to redistribution of PU.1 …

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …

First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al.

2020-Current year OA Pubs

PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the rate of dose-limiting toxicities, adverse events (including immune mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of …

Preparing Spiritually Resilient Warriors In The Canadian Special Operations Forces Command, Vic Morris

Doctor of Ministry Major Applied Project

Morris, Victor E. “Preparing Spiritually Resilient Warriors in the Canadian Special Operations Forces Command.” Doctor of Ministry. Major Applied Project, Concordia Seminary, 2024. 285 pp.

The Canadian Armed Forces has outcomes and expectations for warriors to be spiritually resilient but does not have a training program that has been researched, tested, and validated to achieve this. This study investigates how chaplains can prepare spiritually resilient warriors in CANSOFCOM. A chaplain-led spiritual resilience course was created and delivered to CANSOFCOM members. The course was aligned with the holistic wellness strategy of OPF2, and designed as an inductive, experiential learning experience. An …

Navigating Caregiving: Community Resources And Support Systems For Individuals With Severe Mental Illness Living With Aging Parents, Adam Thai

DNP Qualifying Manuscripts

People with severe mental illness (SMI) who are cared for by aging parents are a growing concern within the community, due to their potential high utilization on healthcare facilities and community infrastructure. Many utilize hospitals and emergency departments to seek behavioral, social, and housing support instead of outpatient behavioral healthcare. There is a disconnect in finding social support that is a result of learned reliance and dependence on their aging parents for financial and caregiving support. Healthcare providers should be mindful of the long-term issues this population faces once they are without parental support, such as increased risks for criminality …

Tnf Prevents Establishment Of Anti-Tumor Immunity And Elucidates Toxicities Following Myxoma Virus Based Oncolytic Virotherapy, Miriam Beatriz Valenzuela Cardenas

Biomedical Sciences ETDs

Tumor Necrosis Factor Alpha (TNF) can lead to tumor regression through its direct cytolytic activity, yet it has also been implicated to facilitate tumor progression. This scenario complicates the efficacy and applicability of TNF based therapeutics as treatment for malignancies. In the context of oncolytic virotherapy (OV) which uses replicating viruses to treat tumors and acts by triggering production of pro-inflammatory cytokines, exploring such mechanisms is vital. Here we show that a Myxoma based oncolytic virus (vPD1/IL12) can induce large amounts TNF. The presence of TNF in the context of vPD1/IL12 plays a detrimental role both for tumor regression by …

Maternal Adverse Childhood Experiences And Infant Visual-Limbic White Matter Development, Catherine H. Demers, Benjamin L. Hankin, Mercedes Hoeflich Haase, Erin Todd, M. Camille Hoffman, C. Neill Epperson, Martin A. Styner, Elysia Poggi Davis

Psychology: Faculty Scholarship

Background

Maternal adverse childhood experiences (ACEs) are robust predictors of mental health for both the exposed individual and the next generation; however, the pathway through which such intergenerational risk is conferred remains unknown. The current study evaluated the association between maternal ACEs and infant brain development, including an a priori focus on circuits implicated in emotional and sensory processing.

Methods

The sample included 101 mother-infant dyads from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Questionnaire dichotomized into low (0 or 1) and high (≥2) groups. White matter microstructure, as indexed by fractional anisotropy (FA), was assessed …

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …

Corneal Transplants And Their Impact, Bianca Estrada

Honors Capstones

A corneal transplant, also called keratoplasty or corneal grafting, is a type of surgery where damaged or diseased corneal tissue is replaced by a healthy donor cornea. The first successful corneal transplant was performed in 1905 by Dr. Eduard Zirm, but since then, surgical advancements have developed greatly, leading to more beneficial outcomes. Corneal blindness is a major form of reversible blindness that is manageable with healthy donor cornea transplantation. Other recipients or possible candidates for corneal transplantation include those with keratoconus, Fuchs’ dystrophy, eye infections, or eye injuries. This remarkable surgery is now one of the most common transplant …

Effects Of Modification In Limonene And Geraniol On The Properties Of Thermal Cured Polyurethane Films, Sauravkumar Rajeshbhai Patel

Electronic Theses & Dissertations

The increasing demand for green materials has inspired in-depth research into biobased polymers; among these polymers, polyurethanes stand out because of their widest range of applications: coatings, adhesives, and biomedical devices. The subject of this paper is the preparation of bio-based polyurethane films based on the polyols synthesized from renewable feedstocks such as limonene, geraniol, and soybean oil. Limonene and geraniol were chemically modified from natural sources such as citrus fruits and essential oils to high-functionality polyols. Characterization of such polyols showed that geraniol had the highest hydroxyl (OH) value and thus geraniol-based polyurethane films were highly influencing in reactivity …