Medicine and Health Sciences Commons^™

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Proteomics Analysis Of Plasma For Risk Of Sepsis: Findings From The Atherosclerosis Risk In Communities Study, Junichi Ishigami, Xiao Hu, Pascal Schlosser, Thomas R Austin, Jingsha Chen, Bruce M Psaty, David Dowdy, Christie M Ballantyne, Morgan E Grams, Josef Coresh, James S Floyd, Kunihiro Matsushita

Faculty, Staff and Students Publications

Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.

Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.

Results: At ARIC visit three, 669 proteins were associated with the risk …

Characteristics And Incidence Of Gastric Cancer Among Patients With Autoimmune And Non-Autoimmune Atrophic Gastritis In A U.S. Population, Mimi C Tan, Kadon N Caskey, Irene Jeong-Ah Lee, Yan Liu, Juan Gomez Cifuentes, Shilpa Jain, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Autoimmune gastritis (AIG) is a risk factor for gastric neuroendocrine tumor (NET). We compared risk factors between AIG cases, non-autoimmune atrophic gastritis (NAIG) cases, and normal controls and determined the incidence of gastric malignancy, including adenocarcinoma and NET.

Methods: We included patients who underwent endoscopy with gastric biopsy between 3/2006 and 9/2021 in Harris Health (Houston, Texas). We identified AIG cases, NAIG cases (gastric atrophy or intestinal metaplasia [GIM] without autoimmune features), and normal controls (without AIG, NIAG, and GIM). A GI pathologist confirmed AIG diagnosis on histopathology report or slide. We determined risk factors of AIG compared to …

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Pharmacologic And Oncohistone Inhibition Of Setd2 Converge On Genomic Instability, Alyssa T Paparella, Ashley G Boice, In Young Park, Rajkishor Nishad, Durga Tripathi, Seth A Nelson, Edward W Pietryk, H Josh Jang, Ian J Frew, W Kimryn Rathmell, Frank M Mason, Cristian Coarfa, Ruhee Dere, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Background/objectives: SETD2 is a dual-function methyltransferase important for methylation of histone H3 at lysine 36 and α-tubulin in spindle microtubules. Genetic inactivation of SETD2 during oncogenesis drives loss of H3K36me3, genomic instability, and cancer progression. This study asked if disruption of genomic stability was a canonical feature of SETD2 inactivation via different pathways.

Methods: We evaluated the impact of EPZ-719, a pharmacologic SETD2 inhibitor, and an H3.3K36M mutant histone ("oncohistone") that binds and sequesters SETD2, on methylation activity and genomic stability in human cell lines. SETD2 activity was measured using in vitro methylation assays, H3K36me3 loss confirmed by Western analysis, …

Ten Years Real-World Experience With Sacubitril/Valsartan In Patients With Heart Failure With Reduced Ejection Fraction, Gianluigi Savarese, Christian Basile, Alexandre Mebazaa, Antoni Bayes-Genis, Seok Min Kang, Byung-Su Yoo, Carlos Eid, Biykem Bozkurt, Javed Butler

Faculty, Staff and Students Publications

Introduction: Sacubitril/valsartan (Sac/Val) represents a cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. This systematic review provides a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sac/Val in patients with HFrEF.

Methods: A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines.

Results: The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac …

Regulating Ai In Pediatrics-Is Transparency Enough?, R Brandon Hunter, Kolaleh Eskandanian, Chester J Koh

Faculty, Staff and Students Publications

No abstract provided.

Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Wenqiang Yin, Kazuo Okamoto, Asuka Terashima, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi

Faculty, Staff and Students Publications

The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we identified Mrep (Ly6ChiCX3CR1loPDPN+CD9+) as a crucial subset of macrophages for muscle regeneration after muscle injury. Muscle regeneration required Mrep-derived activin A, which was produced via the TLR4/TIR domain-containing adapter-inducing interferon-β/TANK-binding kinase 1/interferon regulatory factor 3/7 signaling pathway in response to muscle injury. Mrep exerted pathological effects by secreting activin A in a model of genetically …

Incidence Of Cancers Among Children Living With Hiv In Malawi After Widespread Availability Of Antiretroviral Therapy: A Population-Based Study, Casey L Mcatee, Fatsani Manase, William Kamiyango, Jimmy Villiera, Mark Zobeck, Joseph Mhango, Allison Silverstein, Samuel Maloya, Apatsa Matatiyo, Eluness Simwela, Honour Mhango, Desire Hellings, Brigid O'Brien, Claudia Wallrauch, Tom Heller, Matthew Painschab, Kate Westmoreland, Atupele Mpasa, Rizine Mzikamanda, Nmazuo Ozuah, Joseph Lubega, Nader Kim El-Mallawany, Carl E Allen, Michael E Scheurer

Faculty, Staff and Students Publications

Purpose: Few data describe the modern epidemiology of pediatric HIV-associated cancers in sub-Saharan Africa, home to over 80% of the world's children living with HIV. This study evaluated the incidence of cancers among these children over 15 years after widespread antiretroviral therapy (ART) adoption in Malawi.

Methods: We conducted a retrospective population-based cohort study leveraging multiple independent data sources comprehensive of all cancer diagnoses among children living with HIV in Northern and Central Malawi between 2010 and 2024. HIV-associated cancers were defined as those cancers with well-established epidemiologic associations with HIV. Cumulative incidence and average annual percent change were estimated …

Histone Demethylase Jmjd1a Protects Mice From Enteric Bacterial Infection By Upregulating Ccl8 Expression To Recruit Macrophages And Cd4+ T Cells, Guifang Lin, Lichun Yang, Shuyan Jiang, Yong Zhang, Ping Luo, Weihua Li, Jianming Xu, Gongpeng Xiong, Chundong Yu, Wenbo Chen

Faculty, Staff and Students Publications

Jumonji domain-containing 1A (JMJD1A, also known as KDM3A) is a histone demethylase that specifically demethylates H3K9me1/2 to enhance gene expression. The roles of JMJD1A in many physiological and pathological processes have been revealed. However, it is unclear whether JMJD1A is involved in host defense against enteric pathogen infection. In this study, we found that enteric infection with C. rodentium induced JMJD1A expression in colonic epithelial cells at the transcriptional level partly mediated by IRF1. After C. rodentium infection, JMJD1A-/- mice exhibited increased mortality, colonic injury, and C. rodentium load and systemic spread, suggesting that JMJD1A protects host against C. rodentium …

Online Tutorial On Survival Analysis For Biomarker Discovery, Jaka Kokošar, Ela Praznik, Martin Špendl, Nancy P Moreno, Alana Newell, Gad Shaulsky, Blaž Zupan

Faculty, Staff and Students Publications

In biomedicine, survival analysis addresses time-to-event data to study outcomes like patient survival and treatment response, and supports biomarker discovery. Yet, teaching this analysis is often hindered by mathematical and programming barriers. We present a structured, hands-on tutorial that goes beyond a typical online guide-offering integrated video lectures, literature, quizzes, and practical exercises. Built around Orange Data Mining, an open and free no-code visual analytics platform, the tutorial covers key concepts such as censoring, Kaplan-Meier curves, group comparisons, and biomarker discovery through real-world datasets. Organized in four pedagogical units, it progresses from basic survival data analysis to gene and gene-set …

Examining Sleep-Related Problems In Youth With Misophonia, Kevin M Wagner, Matti Cervin, Catherine E Rast, Mered Parnes, Nicholas Murphy, Samuel Spencer, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

The relationship between misophonia and sleep-related problems (SRPs) in youth is underexplored. This paucity of research is concerning because SRPs might be elevated among youth with misophonia. If left untreated, SRPs can contribute to long-term health consequences. Thus, in this study we examined the link between misophonia and SRPs in youth aged 8 to 17. In this study, we compared SRPs in 102 children and adolescents with clinically significant misophonia to SRPs in a normative youth sample and a sample of 94 youth with anxiety disorders. We also examined the extent to which SRPs were associated with misophonia severity. Approximately …

Risk Factors For Acute Rejection In Pediatric Lung Transplantation And Its Impact On Graft Failure, Sophie Li, Spoorthi Kamepalli, David Moreno Mcneill, Selena Li, Abbas Rana

Faculty, Staff and Students Publications

Background: Although acute rejection is a common complication of lung transplantation, few studies have analyzed risk factors for acute rejection in pediatric lung transplant patients. The purpose of this study was to examine risk and protective factors for acute rejection in pediatric lung transplantation and its impact on graft failure.

Methods: A retrospective analysis was performed on lung transplant data for a cohort of 906 pediatric patients from the Organ Procurement and Transplantation Network (OPTN) Database between October 1, 1987, and June 30, 2023. Multivariable logistic regression was conducted to identify risk and protective factors for acute rejection, adjusting for …

Simulation-Free Spine Palliative Radiotherapy Enabled By Ai-Adapted Diagnostic Ct, Yiding Han, Alexander Nicola Hanania, Zaid Ali Siddiqui, Vincent Ugarte, Boran Zhou, Abdallah S R Mohamed, Piyush Pathak, Daniel Allen Hamstra, Baozhou Sun

Faculty, Staff and Students Publications

Background: Radiotherapy planning traditionally requires a dedicated simulation CT (sCT), which can introduce delays in initiating treatment. This is particularly impactful in spinal palliative care, where timely treatment is often important for symptom control and prevention of neurological deterioration. Although diagnostic CT (dCT) is frequently available earlier in the workflow, it can lead to geometric and dosimetric inaccuracies when used directly for treatment planning due to discrepancies in patient positioning, vertebral alignment, and table curvature.

Purpose: To develop and evaluate an AI-based method that transforms dCT into a simulation-equivalent planning CT (AI-pCT), enabling a clinically feasible simulation-free workflow for spinal …

How Does Frailty Impact Peri-Operative And Speech Recognition Outcomes For Cochlear Implants In Veterans?, Kaitlyn A Brooks, Benjamin D Lovin, Alex D Sweeney, Angela S Peng, Nathan R Lindquist

Faculty, Staff and Students Publications

Objective: To investigate the association of frailty with post-cochlear implant (CI) admission, morbidity, and CI-aided word recognition outcomes in veterans.

Study design: Retrospective cohort.

Setting: Single-institution tertiary care Veterans Health Administration (VHA) hospital.

Methods: Veterans who underwent cochlear implantation between 1998 to 2024 were included. The Modified 5-Item Frailty Index (mFI-5) score was used to characterize preoperative frailty. Outcomes of interest were admission from post-anesthesia care unit (PACU), relative risk (RR) of admission among frail patients, and relationship between frailty and post-CI word recognition score (WRS). Ordinal data were analyzed via logistic regression and Chi square tests; a multivariate linear …

Lean On Me: Social Factors And Diabetes Outcomes Among Young Adults With Type 1 Diabetes Prior To Transitioning To Adult Care, Caroline M Roberts, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Randi Streisand, Barbara J Anderson, Tricia S Tang, Siripoom Mckay, Katherine Gallagher, Sridevi Devaraj, Marisa E Hilliard

Faculty, Staff and Students Publications

Aims: Little is known about how different aspects of social relationships relate to diabetes self-management and glycaemic outcomes in young adults with type 1 diabetes (T1D). We examined relationships of general and diabetes-specific social variables with diabetes self-management and HbA1c. We hypothesized diabetes-specific factors would more strongly associate with self-management and HbA1c than general social factors.

Methods: We analysed baseline data from 100 young adults with T1D (Mage = 19.9 ± 1.3 years) enrolled in a randomized controlled trial of a paediatric to adult care transition intervention. We examined associations of self-reported general and diabetes-specific social factors with self-reported self-management …

Concurrent Vulvar Vitiligo And Lichen Sclerosus: The Importance Of Melanocyte-Specific Immunostains In Resolving Diagnostic Ambiguity, Nabor S Mireles, Kaitlyn Levett, Annie Dai, Abdul Hafeez Diwan, Omid Jalali

Faculty, Staff and Students Publications

Vitiligo and lichen sclerosus (LS) are autoimmune dermatoses that may share overlapping clinical and histopathologic features, posing diagnostic challenges when they occur concurrently. We report a biopsy-confirmed case of vulvar vitiligo and LS in a 61-year-old woman presenting with pruritic, depigmented patches on the labia majora and minora. Histopathologic examination showed epidermal thinning with papillary dermal hyalinization and a dense, band-like lymphocytic infiltrate consistent with LS. Melan-A immunostaining demonstrated a complete absence of epidermal melanocytes, confirming concurrent vitiligo rather than LS-related post-inflammatory hypopigmentation. This case underscores the importance of correlating subtle clinical clues with melanocyte-specific immunostains to distinguish coexistent vitiligo …

Cardiac Catheterization In American Indian/Alaska Native Populations: Empowering Communities, Providers, And Systems Toward Equity, Joseph Burns, Daniel J Penny, Keila N Lopez, Lindsay F Eilers, Athar M Qureshi, Christine J Chung, Jason F Deen

Faculty, Staff and Students Publications

American Indian/Alaska Native (AI/AN) people face numerous health disparities, including alarming rates of cardiovascular morbidity and mortality. These inequities are closely tied to unique social, political, and economic circumstances due to the ongoing consequences of systemic racism. Although poorly described, these cardiovascular inequities extend to adult and pediatric interventional cardiology. AI/AN adults are less likely to undergo cardiac catheterization and are more likely to experience complications. There are no published studies on pediatric interventional cardiology outcomes in AI/AN children. The scarcity of available data underscores the need for novel studies to investigate the epidemiology, sociodemographic associations, and outcomes of AI/AN …

Hes V2.0 Validation And Performance Compared To Galad And Asap In The Heds Cohort, Hashem B El-Serag, Camden Lopez, Michelle Luster, K Rajender Reddy, Neehar Parikh, Amit G Singal, Jorge A Marrero, Aaron P Thrift, Jagpreet Chhatwal, Ziding Feng, Stephanie Page-Lester, Qingchun Jin, Nabihah Tayob, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: We previously developed HES V2.0, a biomarker panel (age, ALT, platelets, etiology, AFP, AFP-L3, DCP, and their 1-year gradients) for early detection of hepatocellular carcinoma (HCC) among patients with cirrhosis. We externally validated HES V2.0 and compared its performance with HES V1.0, GALAD, and ASAP.

Methods: We conducted a PRoBE (prospective specimen-collection, retrospective blinded-evaluation) cohort study in the HEDS (Hepatocellular Carcinoma Early Detection Strategy) cohort of 1,485 patients with cirrhosis, of whom 119 developed HCC. Patient- and test-level true positive rates (TPR) for HCC were calculated at 6, 12, and 24 months before diagnosis, using thresholds at …

Health Care Worker-Reported Barriers And Potential Facilitators Of Acute Lower Respiratory Infection Care Deliver For Children At Mchinji District Hospital In Malawi, Shubhada Hooli, Beatwil Zadutsa, Everlisto Phiri, Karina Hofstee, Nichole Davis, Eric D Mccollum, Charles Makwenda, Carina King

Faculty, Staff and Students Publications

Objectives: We sought to understand barriers to high-quality hospital-based child acute lower respiratory infection (ALRI) care at Mchinji District Hospital in Malawi.

Methods: In 2020, we conducted focus group discussions (FGDs) with clinical officers (COs) who provided direct clinical care after a half-day refresher course on pediatric ALRI case management. The underpinning research methodology of the FGDs was phenomenology, and they were analyzed using inductive and deductive thematic analysis.

Results: We recruited 16 COs to participate in three FGDs. Five themes emerged: lack of confidence in ALRI diagnosis and management, high clinical burden with understaffing, dysfunctional team dynamics, limited physical …

Defining The Society Of Pediatric Liver Transplantation (Split) Research Agenda: A Delphi Consensus Project, Sharad I Wadhwani, Pooja Reddy Spector, Amy G Feldman, Katryn N Furuya, Kayla Hartjes, Chaowapong Jarasvaraparn, Beau Kelly, Stacee M Lerret, Krupa Mysore, Arti Pawaria, Philip Rosenthal, Amy Shui, Voytek Slowik, Sarah Taylor, Jennifer Vittorio, Pamela L Valentino

Faculty, Staff and Students Publications

Background: Despite major advances in surgical and medical management, only one-third of pediatric liver transplant (LT) recipients remain morbidity-free at 10 years. The Society of Pediatric Liver Transplantation (SPLIT) published a research agenda over 10 years ago, and much progress has been made since then. An updated consensus-driven SPLIT research agenda could guide future research and funding priorities. We aimed to identify and prioritize key research needs across the continuum of pediatric LT care using a modified Delphi consensus approach.

Methods: We conducted a three-round modified Delphi process among SPLIT members. In round 1, participants submitted open-ended research priorities. In …

Adenovirus Disease Following Pediatric Liver Transplantation: 10-Year Experience From A Large Pediatric Transplant Program, Anna M Banc-Husu, Sara Hassan, N Thao N Galvan, Elizabeth A Moulton, Jeremy M Schraw, Kathleen Hosek, Dana Cerminara, Flor M Munoz, Krupa Mysore

Faculty, Staff and Students Publications

Background: Human adenovirus in immunocompromised patients can be life-threatening. We describe the prevalence, clinical presentation, and treatment of adenovirus after pediatric liver transplantation at a large transplant center.

Methods: We performed a retrospective cohort study of adenovirus infection in children from 2013 to 2022. We compared incidence, clinical characteristics, and outcomes of post-transplant children by adenovirus treatment status.

Results: Adenovirus disease developed in 26% (84/320) children after liver transplant. Median age at liver transplant was 17.5 months, 48% were female; 50% had biliary atresia. Fever (53%), gastrointestinal symptoms (48%), and hepatitis (41%) were the most common clinical presentations at diagnosis. …

Comparing Observed With Self-Reported Hand Hygiene Adherence Among Bedside Nurses And Physicians At Two Hospitals In The United States, Prathit A Kulkarni, M Todd Greene, Sanjay Saint, Karen E Fowler, Serene Jacob, Laura Dillon, Michelle Espiritu, Nathan Houchens, Huberta T Cozart, Barbara W Trautner

Faculty, Staff and Students Publications

Background: Hand hygiene is a core component of infection prevention in healthcare settings. One potential reason for lack of adherence to recommended hand hygiene practices is erroneous self-perception. We aimed to compare perceptions about hand hygiene compliance with objective data.

Methods: Direct observations of hand hygiene performance by nurses and physicians during typical workflow in inpatient general medicine wards were conducted from 12 September 2022 to 27 October 2022 at two academic Veterans Affairs medical centers. Participants were surveyed regarding perceptions about their hand hygiene performance relative to recommended practices.

Results: Among nurses, hand hygiene was performed in 1,397/3,690 (37.9%) …

Rounding Styles On Inpatient Infectious Disease Consult Services: Impact On Education And Patient-Care Delivery, Melanie Kiener, Vanessa Ku, Prathit A Kulkarni

Faculty, Staff and Students Publications

Inpatient infectious disease (ID) consult services have recently been experiencing increased patient volumes due to a variety of factors, including higher patient complexity, increased patient turnover, growing rates of antimicrobial resistant infections, population aging, and ID outbreaks. As a result, increased time and resources have been required to continue to deliver high-quality medical care to patients. At academic teaching hospitals, providing patient care in the context of increased volumes must be balanced with the educational mission for trainees. Rounding is a central component of ID clinical work which brings together patient care and education. In this narrative review, we aim …

Distributed Battery-Free Bioelectronic Implants With Improved Network Power Transfer Efficiency Via Magnetoelectrics, Joshua E Woods, Fatima Alrashdan, Ellie C Chen, Wendy Tan, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Alexander G Steele, Sean M Barber, Philip J Horner, Amir H Faraji, Dimitry G Sayenko, Mehdi Razavi, Jacob T Robinson

Faculty, Staff and Students Publications

Networks of miniature implants could enable simultaneous sensing and stimulation at different locations in the body, such as the heart and central or peripheral nervous system. This capability would support precise disease tracking and treatment or enable prosthetic technologies with many degrees of freedom. However, wireless power and data transfer are often inefficient through biological tissues, particularly as the number of implanted devices increases. Here we show that magnetoelectric wireless data and power transfer supports a network of millimetre-sized bioelectronic implants in which system efficiency improves with additional devices. We demonstrate wireless, battery-free networks ranging from one to six implants, …

Interpretable Ensemble Machine Learning Prediction Of Nonadherence And The Risk Of Nonpersistence Of Targeted Disease-Modifying Antirheumatic Agents In Older Adults With Rheumatoid Arthritis, Yinan Huang, Sandeep K Agarwal

Faculty, Staff and Students Publications

Purpose: Ensemble machine learning (ML) demonstrated potential for improving predictions based on big health care data. We developed and validated interpretable ensemble ML models in evaluating the nonadherence and nonpersistence of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA).

Methods: This retrospective study used 5% Medicare claims data including older (aged ≥65 years) patients initiating b/tsDMARDs (the index date) between 2013 and 2019, who were diagnosed with RA (the International Classification of Diseases, Ninth and Tenth revision codes). Nonadherence, defined as medication possession ratio < 80%, was evaluated during the 12-month follow-up. Nonpersistence was defined as duration (in days) from the index date until treatment gap ≥60 days during the follow-up period, with death and insurance disenrollment as censoring criteria. Data were split into 75% for model training and 25% for evaluation, with patients' demographics and clinical characteristics measured in the baseline period. Machine learning ensemble classification models (random forest, eXtreme Gradient Boosting [XGBoost], and prediction rule ensembles [PRE]) evaluated the binary nonadherence outcome and ML ensemble survival models (random survival forest, XGBoost survival, and PRE survival) assessed time until nonpersistence. Using the testing cohort, concordance index (C-index) was reported for the ML survival models and AUC was reported for ML classification models.

Findings: We identified 3927 eligible patients with RA (mean age 73 ± …

Comparison Of Opioid Utilization In Older Adults With Rheumatoid Arthritis Before And After Initiating Biological Or Targeted Synthetic Disease-Modifying Antirheumatic Drugs, Yinan Huang, Shadi Bazzazzadehgan, Liang-Yuan Lin, Omkar Ghodke, Sebastian Bruera, Kaustuv Bhattacharya, Sujith Ramachandran, John P Bentley, Sandeep K Agarwal, Yi Yang

Faculty, Staff and Students Publications

Introduction: Opioid use is common in rheumatoid arthritis (RA) for pain management; however, evidence of opioid-associated adverse events is increasing. While biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) improve functional outcomes such as pain, little is known about their impact on opioid utilization patterns. This study investigated opioid utilization before and after b/tsDMARD initiation and assessed effect modification by sex.

Methods: Using 5% Medicare claims data from 2012 to 2020, this cohort study included older adults (≥ 65 years) with RA who initiated b/tsDMARDs (first prescription = index date), and had continuous Medicare Parts A, B, and …

Segmental And Multifocal Isolated Dystonias: Similarities And Differences, Hyder A Jinnah, Vittorio Velucci, Daniele Belvisi, Gamze Kilic-Berkmen, Joel S Perlmutter, Laura J Wright, Christine Klein, Jeanne S Feuerstein, Steven Bellows, Joseph Jankovic, Cynthia Comella, Richard L Barbano, Aparna Wagle Shukla, Stephen G Reich, Mark S Ledoux, Alberto J Espay, Kevin R Duque, Florence C F Chang, Victor S C Fung, Sarah Pirio-Richardson, Carmen Terranova, Emile S Moukheiber, Sarah Idrissi, Barbara Vitucci, Susan H Fox, Samuel Frank, Natividad Stover, Brian D Berman, Rachel Saunders-Pullman, William G Ondo, Christopher L Groth, Marcello Esposito, Laura Avanzino, Francesco Bono, Roberto Erro, Marcello Mario Mascia, Antonella Muroni, Alfredo Berardelli, Giovanni Defazio

Faculty, Staff and Students Publications

Background: Whether the traditional distinction between segmental and multifocal dystonia is clinically or scientifically useful remains unclear.

Objective: To evaluate whether idiopathic isolated adult-onset segmental and multifocal dystonia can be differentiated based on clinical features other than the contiguity of affected body regions.

Methods: We compared data on segmental and multifocal dystonia from two large dystonia databases established in the USA and Italy that used similar criteria for patient recruitment and assessment.

Results: Compared to segmental dystonia, multifocal dystonia was characterized by a higher proportion of men, a younger age at dystonia onset, a greater frequency of upper limb dystonia, …

Impulsivity In Cerebellar Ataxia: An Online, Multidimensional Assessment, Brooke Chasalow, Yakov Flaumenhaft, Yael De Picciotto, Chi-Ying R Lin, Leila Montaser-Kouhsari, William Saban

Faculty, Staff and Students Publications

While considered a motor control structure, the cerebellum contributes to non-motor functions, including impulsivity. However, whether it contributes to impulsivity in a domain-specific manner remains unknown. Studies on cerebellar ataxia (CA), a common model for cerebellar dysfunction, typically have small sample sizes, limiting robustness. In a multicenter cross-sectional study, we investigated the cerebellum's role in various forms of impulsivity by comparing large cohorts of CA to age- and education-matched neurotypical healthy (NH) controls. Additionally, to examine the ability to identify individuals with CA using impulsivity features alone, we developed supervised machine learning (ML) models. In experiment 1 (CA = 140, …

Pharmacodynamics, Efficacy, And Safety Of Intraputaminal Eladocagene Exuparvovec Administered To Pediatric Patients With Aromatic L-Amino Acid Decarboxylase Deficiency Using An Mr-Compatible Cannula: 48 Weeks Of Follow-Up, Daniel J Curry, Phillip L Pearl, Scellig S D Stone, Donald L Gilbert, Sudhakar Vadivelu, Bruria Ben-Zeev, Matthew Vestal, Muhammad Zafar, Chun-Hwei Tai, Sheng-Che Chou, Zion Zibly, Lior Ungar, Mered Parnes, Mariam Hull, Lisa Emrick, Christian Werner, Alexis Krolick, Vinay Penematsa, Antonia Wang, Rezwanur Rahman, Lee Golden, Yin-Hsiu Chien, Paul Wuh-Liang Hwu

Faculty, Staff and Students Publications

Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT‐002 (NCT04903288) is a phase 2, multicenter, open‐label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)‐compatible cannula. Patients received eladocagene exuparvovec at 1.8 × 1011 vector genomes via the SmartFlow MR‐compatible cannula in a single operative session. Endpoints include the change from baseline in …