Digital Commons Network^™

Cryptic Bacterial Pathogens Of Diatoms Peak During Senescence Of A Winter Diatom Bloom, Laura Branscombe, Ellen L. Harrison, Zhi Yi Daniel Choong, Courtney Swink, Matthew Keys, Claire Widdicombe, William H. Wilson, Michael Cunliffe, Katherine Helliwell

School of Biological and Marine Sciences

Summary.Diatoms are globally abundant microalgae that form extensive blooms in aquatic ecosystems. Certain bacteria behave antagonistically towards diatoms, killing or inhibiting their growth. Despite their crucial implications to diatom bloom and population health, knowledge of diatom antagonists in the environment is fundamentally lacking. We report systematic characterisation of the diversity and seasonal dynamics of bacterial antagonists of diatoms via plaque assay sampling in the Western English Channel, where diatoms frequently bloom. Unexpectedly, peaks in detection did not occur during characteristic spring diatom blooms, but coincided with a winter bloom of Coscinodiscus, suggesting that these bacteria likely influence distinct diatom host …

Anticoagulation For Atrial Fibrillation After Cardiac Surgery: Do Guidelines Reflect The Evidence?, Subhasis Chatterjee, Niv Ad, Vinay Badhwar, A Marc Gillinov, John H Alexander, Marc R Moon

Faculty, Staff and Students Publications

No abstract provided.

February 1, 2024, James Madison University

The Breeze, 2020-

The Breeze is the student newspaper of James Madison University in Harrisonburg, Virginia.

Envy Influences Interpersonal Dynamics And Team Performance: Roles Of Gender Congruence And Collective Team Identification, Kenneth Tai, Sejin Keem, Ki Young Lee, Eugene Kim

Research Collection Lee Kong Chian School Of Business

Our research extends past envy research by considering how envy and gender congruence shape interpersonal dynamics at the dyadic level and their bottom-up effects for team performance. Integrating social comparison theory and social identity theory, we examine when and how dyadic level envy influences team performance. Using time-lagged data from 428 dyads of 161 employees in 51 teams, our results show that envious employees are likely to engage in interpersonal deviance directed toward envied team members and that envied employees are likely to seek advice from envious team members. Gender congruence further influences these relationships, with different patterns for males …

Association Between Hba1c And Deep Sternal Wound Infection After Coronary Artery Bypass: A Systematic Review And Meta-Analysis, Wenyu Zhao, Jingui Xie, Zhichao Zheng, Han Zhou, Oon Cheong Ooi, Haidong Luo

Research Collection Lee Kong Chian School Of Business

Background: Deep sternal wound infection (DSWI) constitutes a serious complication after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the dose-response relationship between glycated hemoglobin (HbA1c) level and the risk of DSWI after CABG. Methods: PubMed, Scopus, and Cochrane Library databases were searched to identify potentially relevant articles. According to rigorous inclusion and exclusion criteria, fourteen studies including 15,570 patients were finally enrolled in our meta-analysis. Odds ratio (OR) with 95% confidence intervals (CIs) was used as the summary statistic. The robust-error meta-regression model was used to synthesize the dose-response relationship. Results: Our meta-analysis …

Vaccine Immunogenicity Versus Gastrointestinal Microbiome Status: Implications For Poultry Production, Chrysta N. Beck, Jiangchao Zhao, Gisela F. Erf

Poultry Science Faculty Publications and Presentations

At the turn of the 21st century, the importance of maintaining a balanced microbiome was brought to the forefront of the microbiology, immunology, and physiology research fields. Exploring the complex interactions between vaccine administration, mucosal microbiome, oral tolerance, and enteric inflammation in health and disease is challenging since environmental factors (such as diet and sanitation) have major influences on gut microbiota composition. High enteric pathogen load has been shown to contribute to dampened cell-mediated and humoral immune responses to vaccines in human case studies, either through elevated enteric inflammation or increased tolerance to environmental microbes. Although antibiotic and probiotic interventions …

Antimicrobial Tolerance In Salmonella: Contributions To Survival And Persistence In Processing Environments, Tomi Obe, Aaron S. Kiess, Ramakrishna Nannapaneni

Poultry Science Faculty Publications and Presentations

Salmonella remains a top bacterial pathogen implicated in several food-borne outbreaks, despite the use of antimicrobials and sanitizers during production and processing. While these chemicals have been effective, Salmonella has shown the ability to survive and persist in poultry processing environments. This can be credited to its microbial ability to adapt and develop/acquire tolerance and/or resistance to different antimicrobial agents including oxidizers, acids (organic and inorganic), phenols, and surfactants. Moreover, there are several factors in processing environments that can limit the efficacy of these antimicrobials, thus allowing survival and persistence. This mini-review examines the antimicrobial activity of common disinfectants/sanitizers used …

Accelerating Neurotechnology Development Using An Agile Methodology, Anil Kumar Thota, Ranu Jung

Biomedical Engineering Faculty Publications and Presentations

Novel bioelectronic medical devices that target neural control of visceral organs (e.g., liver, gut, spleen) or inflammatory reflex pathways are innovative class III medical devices like implantable cardiac pacemakers that are lifesaving and life-sustaining medical devices. Bringing innovative neurotechnologies early into the market and the hands of treatment providers would benefit a large population of patients inflicted with autonomic and chronic immune disorders. Medical device manufacturers and software developers widely use the Waterfall methodology to implement design controls through verification and validation. In the Waterfall methodology, after identifying user needs, a functional unit is fabricated following the verification loop (design, …

Effects Of Environmental Enrichments On Welfare And Hepatic Metabolic Regulation Of Broiler Chickens, Seong W. Kang, Karen D. Christensen, Michael T. Kidd, Sara K. Orlowski

Poultry Science Faculty Publications and Presentations

The aims of this study were to find suitable environmental enrichment (EE) and evaluate the combined effect of two EEs, variable light intensity (VL) lighting program and EH, on mental health and hepatic metabolic regulation in commercial broilers. To find the advantageous EEs for broilers, three different EEs (board, hut, and ramp) were tested in trial 1. EEs were placed and the engagement of birds to EEs, dustbathing behavior, and daily physical activity were observed. Birds treated with huts showed higher engagement than the board- or ramp-treated birds (p < 0.05). The results of dustbathing behavior and daily physical activity indicated that the environmental hut (EH) is the most favorable enrichment for broilers. In the second trial, to test the effect of EHs on mental health and hepatic metabolic conditions, the brain and liver were sampled from the four treatment birds (20 lx_Con, 20 lx_Hut, VL_Con and VL_Hut) on day 42. The lower expression of TPH2 (tryptophan hydroxylase 2) of VL_Hut birds than those of VL_Con and 20 lx_Hut treated birds suggests the combining effect of EHs with the VL lighting program on the central serotonergic homeostasis of broilers. Reduced expressions of TH (tyrosine hydroxylase), GR (glucocorticoid receptor), BDNF (brain-derived neurotrophic factor) of VL_Hut treated birds compared to those of VL_Con and 20 lx_Hut birds suggest lower stress, stress susceptibility, and chronic social stress in VL_Hut treated birds. The expression of CPT1A (carnitine palmitoyl transferase 1) increased over three-fold in the liver of VL_Con birds compared to 20 lx_Con birds (p < 0.05). EHs treatment in VL birds (VL_Hut) significantly decreased CPT1A but not in 20 lx birds (20 lx_Hut). The expression of ACCα (acetyl-CoA carboxylase alpha) was significantly decreased in VL_Con birds compared to 20 lx_Con birds. There was no significant difference in the hepatic FBPase (fructose-1,6-bisphosphatase), GR, and 11β-HSD1 (11 β-hydroxysteroid dehydrogenease-1) expression between 20 lx_Con and VL_Con birds, but EHs significantly stimulated GR in 20 lx_Hut birds, and stimulated FBPase and 11β-HSD1 expression in the VL_Hut birds compared to 20 lx_Con birds, suggesting that the VL lighting program reduced fatty acid synthesis and increased fatty acid β-oxidation in the broilers’ liver and VL_Hut improved the hepatic de novo glucose production. Taken together, the results suggest that the stimulated voluntary activity by EHs in the light-enriched broiler house improved mental health and hepatic metabolic function of broilers and may indicate that the improved hepatic metabolic function contributes to efficient nutritional support for broilers.

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Antiviral Potency Of Long-Acting Islatravir Subdermal Implant In Shiv-Infected Macaques, Fernanda P Pons-Faudoa, Nicola Di Trani, Simone Capuani, Ilaria Facchi, Anthony M Wood, Bharti Nehete, Ashley Delise, Suman Sharma, Kathryn A Shelton, Lane R Bushman, Corrine Ying Xuan Chua, Michael M Ittmann, Jason T Kimata, Peter L Anderson, Pramod N Nehete, Roberto C Arduino, Alessandro Grattoni

Faculty, Staff and Student Publications

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded …

Should Secondary Pharmacogenomic Variants Be Actively Screened And Reported When Diagnostic Genome-Wide Sequencing Is Performed In A Child?, Jan M Friedman, Yvonne Bombard, Bruce Carleton, Amalia M Issa, Bartha Knoppers, Sharon E Plon, Vasiliki Rahimzadeh, Mary V Relling, Marc S Williams, Clara Van Karnebeek, Danya Vears, Martina C Cornel

Center for Medical Ethics and Health Policy Staff Publications

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over …

Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Mark P Hamilton, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Zika virus congenital infection evades double-stranded RNA detection and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. Understanding how viruses can persist and replicate in the placenta without causing overt cellular or tissue damage is fundamental to deciphering mechanisms of maternal-fetal vertical transmission.

OBJECTIVE: Placenta-specific microRNAs are believed to be a tenet of viral resistance at the maternal-fetal interface. We aimed to test the hypothesis that the Zika virus functionally disrupts placental microRNAs, enabling viral persistence and fetal pathogenesis.

STUDY DESIGN: To test this hypothesis, we used orthogonal approaches in human and …

The Curious Case Of A Painful Leg Ulcer, Jay R Patel, Rubi Montejano, Christina Hopkins, Hanna Siatecka, Theodore Rosen

Faculty, Staff and Students Publications

Sickle cell disease is a condition that can involve numerous organ systems secondary to vascular occlusion. Herein, we present a case of a 21-year-old male with sickle cell disease requiring long-term hydroxyurea therapy. Upon migrating to the United States from Yemen, the patient developed a rapidly progressive, exquisitely painful ulcer on his right lower extremity. Given his country of origin, a broad differential, including select infectious diseases, was essential. Moreover, establishing the unequivocally correct diagnosis was crucial to determine proper and safe therapy. Ultimately, a lesional biopsy demonstrated numerous sickled red blood cells occluding blood vessels, leading to the diagnosis …

Offloading And Adherence Through Technological Advancements: Modern Approaches For Better Foot Care In Diabetes, Sicco A Bus, Neil D Reeves, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Objective: This manuscript aims to provide a review and synthesis of contemporary advancements in footwear, sensor technology for remote monitoring, and digital health, with a focus on improving offloading and measuring and enhancing adherence to offloading in diabetic foot care.

Methods: A narrative literature review was conducted by sourcing peer-reviewed articles, clinical studies, and technological innovations. This paper includes a review of various strategies, from specifically designed footwear, smart insoles and boots to using digital health interventions, which aim to offload plantar pressure and help prevent and manage wounds more effectively by improving the adherence to such offloading.

Results: In-house …

Brief Report: Comprehensive Clinicogenomic Profiling Of Small Cell Transformation From Egfr-Mutant Nsclc Informs Potential Therapeutic Targets, Bingnan Zhang, Whitney Lewis, C Allison Stewart, Benjamin B Morris, Luisa M Solis, Alejandra Serrano, Yuanxin Xi, Qi Wang, Elyse R Lopez, Kyle Concannon, Simon Heeke, Ximing Tang, Gabriela Raso, Robert J Cardnell, Natalie Vokes, George Blumenschein, Yasir Elamin, Frank Fosella, Anne Tsao, Ferdinandos Skoulidis, Celyne Bueno Hume, Koji Sasak, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Hai Tran, Jianjun Zhang, Don Gibbons, Ara Vaporciyan, Jing Wang, Keunchil Park, John V Heymach, Lauren A Byers, Carl M Gay, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION: NSCLC transformation to SCLC has been best characterized with

METHODS: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with

RESULTS: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC …

Association Between Circulating Inflammatory Markers And Adult Cancer Risk: A Mendelian Randomization Analysis, James Yarmolinsky, Jamie W Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Niki Dimou, Neil Murphy, Kimberley Burrows, Emmanouil Bouras, Karl Smith-Byrne, Sarah J Lewis, Tessel E Galesloot, Lambertus A Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A Newcomb, Emily White, Alicja Wolk, Anna H Wu, Loïc Le Marchand, Amanda I Phipps, Daniel D Buchanan, International Lung Cancer Consortium, Practical Consortium, Sizheng Steven Zhao, Dipender Gill, Stephen J Chanock, Mark P Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I Amos, Rayjean J Hung, Abbas Dehghan, Mattias Johansson, Marc J Gunter, Kostas K Tsilidis, Richard M Martin

Faculty, Staff and Student Publications

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were …

Implementation And Evaluation Of A Mhealth-Based Community Health Worker Feedback Loop For Hispanics With And At Risk For Diabetes, Elizabeth M Vaughan, Victor J Cardenas, Wenyaw Chan, Amber B Amspoker, Craig A Johnston, Salim S Virani, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Gaps in accessibility and communication hinder diabetes care in poor communities. Combining mobile health (mHealth) and community health workers (CHWs) into models to bridge these gaps has great potential but needs evaluation.

OBJECTIVE: To evaluate a mHealth-based, Participant-CHW-Clinician feedback loop in a real-world setting.

DESIGN: Quasi-experimental feasibility study with intervention and usual care (UC) groups.

PARTICIPANTS: A total of 134 participants (n = 67/group) who were all low-income, uninsured Hispanics with or at-risk for type 2 diabetes.

INTERVENTION: A 15-month study with a weekly to semimonthly mHealth Participant-CHW-Clinician feedback loop to identify participant issues and provide participants monthly diabetes …

Novel Hemizygous Single-Nucleotide Duplication In Rpgr In A Patient With Retinal Dystrophy And Sensorineural Hearing Loss, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Nichole Owen, Richard A Lewis, Lisa Saba, Texome Project, Michael F Wangler, Sandesh Nagamani

Duncan NRI Faculty and Staff Publications

Background: The RPGR gene has been associated with X-linked cone-rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel-based testing and thus genome-wide tests such as ES may be required for accurate diagnosis.

Methods: The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care.

Results: A 58-year-old male presented with retinitis pigmentosa, sensorineural hearing loss, and …

Matr3 Pathogenic Variants Differentially Impair Its Cryptic Splicing Repression Function, Mashiat Khan, Xiao Xiao Lily Chen, Michelle Dias, Jhune Rizsan Santos, Sukhleen Kour, Justin You, Rebekah Van Bruggen, Mohieldin M M Youssef, Ying-Wooi Wan, Zhandong Liu, Jill A Rosenfeld, Qiumin Tan, Udai Bhan Pandey, Hari Krishna Yalamanchili, Jeehye Park

Duncan NRI Faculty and Staff Publications

Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research …

Determinants Of Referral Network Size For Screening Colonoscopies In The Veterans Health Administration After The Implementation Of The Mission Act, Chase S Eck, Vivian Ho, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To measure key characteristics of the Veterans Health Administration's (VHA) Community Care (CC) referral network for screening colonoscopy and identify market and institutional factors associated with network size.

Data sources: VHA electronic health records, CC claim data, and National Plan and Provider Enumeration System.

Study design: In this retrospective cross-sectional study, we measure the size of the VHA's CC referral networks over time and by VHA parent facility (n = 137). We used a multivariable linear regression to identify factors associated with network size at the market-year level. Network size was measured as the number of physicians who performed …

Left Main Coronary Artery Disease: A Contemporary Review Of Diagnosis And Management, Muzamil Khawaja, Michael Britt, Muhammad Asad Khan, Uzair Munaf, Hassaan Arshad, Rehma Siddiqui, Hafeez Ul Hassan Virk, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Significant left main coronary artery disease is a very high-risk subgroup of coronary artery disease that is a crucial indicator of heightened morbidity and mortality rates. Despite its clinical significance, uncertainties persist regarding the optimal management strategy for patients, particularly given its phenotypic variations. Existing evidence-based guidelines offer insights into revascularization options, yet questions remain regarding long-term prognoses and clinical outcomes when comparing percutaneous coronary intervention to coronary artery bypass grafting. This comprehensive review aims to provide an in-depth analysis of contemporary strategies for the diagnosis, assessment, and treatment of left main coronary artery disease. By synthesizing current literature and …

Gene-Specific Acmg/Amp Classification Criteria For Germline Apc Variants: Recommendations From The Clingen Insight Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel\, Isabel Spier, Xiaoyu Yin, Marcy Richardson, Marta Pineda, Andreas Laner, Deborah Ritter, Julie Boyle, Pilar Mur, Thomas V O Hansen, Xuemei Shi, Khalid Mahmood, John-Paul Plazzer, Elisabet Ognedal, Margareta Nordling, Susan M Farrington, Gou Yamamoto, Stéphanie Baert-Desurmont, Alexandra Martins, Ester Borras, Carli Tops, Erica Webb, Victoria Beshay, Maurizio Genuardi, Tina Pesaran, Gabriel Capellá, Sean V Tavtigian, Andrew Latchford, Ian M Frayling, Sharon E Plon, Marc Greenblatt, Finlay A Macrae, Stefan Aretz, Insight-Clingen Hereditary Colon Cancer/Polyposis Variant Curation Expert Panel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome.

Methods: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants.

Results: The APC-specific criteria …

Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention.

METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, …

Utility Of A Low-Cost 3-D Printed Microscope For Evaluating Esophageal Biopsies, Daniel G Rosen, Evandro Sobroza De Mello, Sadhna Dhingra, Sanford M Dawsey, Joe Knapper, Richard Bowman, Sharmila Anandasabapathy

Center for Medical Ethics and Health Policy Staff Publications

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost …

Veterans Health Administration Enrollees’ Choice Of Care Setting Relates To The Expansion Of Care Options: Evidence From Screening Colonoscopies Before And After The Mission Act, Chase S Eck, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To estimate whether those enrolled in the Veterans Health Administration (VHA) were less likely to use VHA-delivered colorectal cancer screening colonoscopies after the MISSION Act.

Data sources and study setting: Secondary data were collected on VHA-enrolled Veterans from FY2017-FY2021.

Study design: This retrospective cross-sectional study measured the volume and share of screening colonoscopies that were VHA-delivered over time and by drive time eligibility-defined as living more than 60 min away from the nearest VHA specialty-care clinic. We used a multivariable logistic regression to adjust for patient and facility factors.

Data extraction: Data were extracted for VHA enrollees (n = …

Personalized Roadmaps For Returning Results From Digital Phenotyping, Kristin Marie Kostick-Quenet, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Sirt1 Safeguards Adipogenic Differentiation By Orchestrating Anti-Oxidative Responses And Suppressing Cellular Senescence, An Yu, Ruofan Yu, Haiying Liu, Chenliang Ge, Weiwei Dang

Faculty, Staff and Students Publications

Adipose tissue is an important endocrine organ that regulates metabolism, immune response and aging in mammals. Healthy adipocytes promote tissue homeostasis and longevity. SIRT1, a conserved NAD⁺-dependent deacetylase, negatively regulates adipogenic differentiation by deacetylating and inhibiting PPAR-γ. However, knocking out SIRT1 in mesenchymal stem cells (MSCs) in mice not only causes defects in osteogenesis, but also results in the loss of adipose tissues, suggesting that SIRT1 is also important for adipogenic differentiation.

Here, we report that severe impairment of SIRT1 function in MSCs caused significant defects and cellular senescence during adipogenic differentiation. These were observed only when inhibiting …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …