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Selenium And Liver Steatosis And Fibrosis: Opposing Direct And Steatosis-Mediated Associations In A Large Cohort, Neda Rehan, Jubilee Benedict, Rehan Qayyum

Department of Medicine Faculty Publications

Background and Aims

Epidemiologic studies have reported conflicting associations between selenium exposure and liver disease. Whether selenium exerts opposing direct and steatosis-mediated effects on liver fibrosis is unknown. To evaluate the associations of blood selenium with elastography-defined hepatic steatosis and fibrosis and to determine whether hepatic steatosis mediates the relationship between selenium and fibrosis.

Methods

We conducted a cross-sectional analysis of adults aged >= 18 years in NHANES 2017-2023. Hepatic steatosis was assessed using the controlled attenuation parameter (CAP) and fibrosis using liver stiffness measurement (LSM). Blood selenium was categorized into quartiles. Survey-weighted multivariable linear regression and structural equation modeling …

Seasonal And Geographic Patterns Of Gastroschisis In Canada: Protective Effect Of Periconceptional Sunlight Exposure, Shiliang Liu, Shin Jie Yong, Dunjin Chen, Gavin C. Hughes, Claude L. Hughes

Department of Medicine Faculty Publications

Background: Gastroschisis is a right-sided, full-thickness defect with extra-amnionic herniation of abdominal contents directly into the amniotic cavity. The causes of gastroschisis remain obscure. We hypothesized that limited periconceptional sunlight exposure might lead to insufficient vitamin D during fetal development and play a role in gastroschisis etiology.

Methods: We conducted a population-based cohort study of infants conceived in Canada between April 2006 and March 2020. We used winter months (i.e., November and December) and northern geographic latitudes as indicators of insufficient sunlight exposure, while summer months (July and August) and southern geographic latitudes were considered as reference. We examined the …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …

An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis

Department of Medicine Faculty Publications

Background: Cancer and heart failure (HF) are highly prevalent in the population and can co-exist, due to shared risk factors and an aging population. The HF-related mortality burden in cancer patients across in the United States (US) remains poorly understood. The goal of this study is to evaluate the patterns of HF-related deaths among cancer patients in the United States.

Methods: A retrospective analysis was performed using the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death database between years 1999 and 2020. HF-related deaths were defined as death certificates listing HF as a contributing cause of …

Dampak Peraturan Daerah Terkait Kesehatan Terhadap Prevalensi Stunting Tingkat Kabupaten/Kota Di Indonesia, Cakra Yudi Putra, Teguh Dartanto

Jurnal Ekonomi dan Pembangunan Indonesia

Stunting remains a major public health challenge in Indonesia with long-term impacts on health, cognition, and productivity. This study examines whether health-related regional regulations (Peraturan Daerah or Perda) reduce stunting prevalence across 338 districts/municipalities in 2007 and 2013. Using Difference-in-Differences (DiD) and DiD with Propensity Score Matching (DiD-PSM) on secondary data from Riskesdas, Statistics Indonesia (BPS), and the Legal Documentation and Information Network (JDIH), we find no statistically significant causal effect of cumulative health Perda on stunting reduction, although OLS shows a negative association. Sanitation significantly reduces stunting in eastern Indonesia. Findings highlight the need for evidence-based, multisectoral, measurable, implementable, …

Markov Chain Wave Generative Adversarial Network For Bee Bioacoustic Signal Synthesis, Kumudu Samarappuli, Iman Ardekani, Mahsa Mohaghegh, Abdolhossein Sarrafzadeh

Electrical & Computer Engineering Faculty Publications

This paper presents a framework for synthesizing bee bioacoustic signals associated with hive events. While existing approaches like WaveGAN have shown promise in audio generation, they often fail to preserve the subtle temporal and spectral features of bioacoustic signals critical for event-specific classification. The proposed method, MCWaveGAN, extends WaveGAN with a Markov Chain refinement stage, producing synthetic signals that more closely match the distribution of real bioacoustic data. Experimental results show that this method captures signal characteristics more effectively than WaveGAN alone. Furthermore, when integrated into a classifier, synthesized signals improved hive status prediction accuracy. These results highlight the potential …

Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality. Sorafenib is the current first-line oral therapy; however, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and gastrointestinal instability. This study aimed to develop a pH-responsive nano-in-microparticle delivery system using a single-step droplet-based microfluidic process to protect sorafenib in the gastric environment and achieve controlled release for enhanced oral chemotherapy. Sorafenib-loaded ZIF-8 nanoparticles (SZ NPs) were synthesized and characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD), exhibiting a mean diameter of about 72 nm and …

Mtl_Tx: A Multi-Task Transformer Model For Improved Radiation Time-Series Estimation, Hongfang Zhang, Adam Stavola, Hal Ferguson, Bence Budavari, Hongyi Wu, Chiman Kwan, Jiang Li

Electrical & Computer Engineering Faculty Publications

Controlling radiation doses at potential radioactive facilities is critical to ensuring the safety of both personnel and the public. At the Thomas Jefferson National Accelerator Facility (JLab), multiple sensors are deployed around the three experimental halls to monitor key parameters, including single-beam current, energy levels, current leakage, and radiation values during accelerator operations. In this study, we developed a Multi-task Transformer model, MTL_TX, to accurately estimate radiation doses at sensor locations based on historical data, with the aim of enhancing safety in accelerator facilities and surrounding public areas. To improve estimation accuracy, we integrated two innovative components into the proposed …

Pin-Plane Electrical Discharge Driven By A Mosfet Dc Current Source, Myles Perry, Sidmar Holoman, Daniel Wozniak, Shirshak Kumar Dhali

Electrical & Computer Engineering Faculty Publications

The generation of atmospheric pressure nonequilibrium plasma using electrical discharges is an active area of research due to its significance in a wide spectrum of applications including medicine, combustion, and manufacturing. In our attempt to create a helium plasma jet in a pin-plane discharge with a constant current source, we observed self-pulsating behavior. We present the results of the electrical, optical, and spectroscopic measurements carried out to characterize the discharge. The duration of the discharge is a few tens of nanoseconds, and the repetition rate is in the few tens of kHz. The effect of the gap distance and gas …

An Explainable Cs-Mitigation Triangular (Ecsmt) Framework To Secure Graph Neural Networks, Sabah Ettahri, Sergio Pallas Enguita, Chung-Hao Chen, Wen-Chao Yang

Electrical & Computer Engineering Faculty Publications

This research addresses cyber risk by defending against backdoor attacks on Graph Neural Networks (GNNs). We propose the Explainable Complex System-Mitigation Triangular (ECSMT) Framework, which integrates Robust Training, Graph Regularization, and Data Sanitization into a lightweight, hardware-efficient defense layer. To evaluate structural generalizability, we conducted empirical evaluations across three distinct benchmark domains (AIDS, MUTAG, and PROTEINS) using a Graph Isomorphism Network (GIN) backbone. Under a baseline 5% backdoor subgraph trigger injection ratio, ECSMT achieves excellent utility retention, securing a Clean Accuracy (CA) of 97.33% (±0.62%) while reducing the Attack Success Rate (ASR) from 97.00% down to 69.45% on the primary …

Application Of A Hyaluronic Acid-Based Lotions Containing Hydroxyapatite Nano-Particles Approach For Treatment Of Initial Dental Caries, Zahra Gharavi, Zahra Namazi, Fatemehsadat Pishbin, Helia Givian, Maryam Torshabi, Farhood Najafi, Parisa Amdjadi

Electrical & Computer Engineering Faculty Publications

This study evaluated the remineralization potential of a ceramic–polyelectrolyte system, based on a novel combination of hydroxyapatite nanoparticles (HAp NPs) and a hyaluronic acid (HY) matrix, for dental enamel, a tissue that remains challenging to repair in clinical dentistry. Nano-Hydroxyapatite (nanoHAp) powder was synthesized and characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and zeta potential analysis to confirm their crystalline structure, functional groups, morphology, particle size distribution, and colloidal stability. HY-based suspensions (remineralizing lotions) containing 5, 10, and 12 wt% of the synthesized nanoHAp particles were formulated via a …

First Report Of A Trematode Infection In An Invasive Population Of Pomacea Maculata: Evidence Of A Phaneropsolid (Trematoda: Microphalloidea) And Recommended Methods For Surveillance, Jonah A. Nguyen, Lori Tolley-Jordan, Annie P. Slayton, Bradley M. Richardson, Thomas G. Rosser

Research, Publications & Creative Work

Giant apple snails, Pomacea maculata (Caenogastropoda: Ampullariidae), are native to South America but are now invasively established in subtropical freshwater habitats worldwide. In May 2017, P. maculata from an urban pond in Mobile, Alabama, USA were found infected with a larval trematode, prompting further collections to determine prevalence and investigate effects of infection by snail sex and size. In total, 284 snails (n = 184 female, n = 100 male) were collected in May, August, and October of 2017 and 2018. Of these, 60 females and 23 males were infected with prevalence per sampling event ranging from 4 to …

Skin Type Diversity In Image Datasets, Neda Alipour

Doctoral

Image-based AI systems that analyse human skin are increasingly used in healthcare and computer vision applications. However, many human skin-based image datasets do not provide reliable information about skin type, making it difficult to assess whether these systems perform consistently across the full spectrum of skin colour. The objective of this thesis is to examine how skin type diversity is represented and measured in image datasets, and to evaluate the reliability of image-based skin type measurement methods under different imaging conditions. Using publicly available skin lesion image datasets as a well-defined and widely used sub-class of skin image datasets, this …

Will They Be More Honest With An (External) Proctor? Evaluating Ufc Match Performance Before And After The Adoption Of The Usada Doping Program, Moonsup Hyun, Wonsok (Frank) Jee, Sehwon Kang, Yohan Lee

Human Movement Studies & Special Education Faculty Publications

Over the eight years from 2015 to 2023, the Ultimate Fighting Championship (UFC) partnered with the United States Anti-Doping Agency (USADA) to institute comprehensive external oversight of doping controls. This study investigates the effects of transitioning from internally administered anti-doping protocols to exclusive external governance by comparing UFC performance metrics before and during the USADA partnership. Using a Difference-in-Differences (DiD) approach with data from 2012 to 2018, we find that match duration significantly increased, while the likelihood of extreme outcomes, knockouts (KO), technical knockouts (TKO), and submissions, decreased during the USADA period. These results suggest that performance-enhancing drugs (PEDs) could …

Joint Associations Of Meditation And Physical Activity With Depression And Anxiety Symptoms In Us Adults: Nhis 2022, Yubing Wang

Human Movement Studies & Special Education Faculty Publications

Objectives

Physical activity and meditation may each relate to mental health, but their joint associations in U.S. adults are unclear. We examined the separate and joint associations of any past-year meditation and meeting physical activity (PA) guidelines with depression and anxiety symptoms.

Method

We analyzed data from the 2022 National Health Interview Survey Sample Adult file (n = 24,927). Exposures were meeting PA guidelines, any past-year meditation, and their four-level combination (Neither, PA only, Meditation only, Both). Outcomes were moderate-to-severe depressive and anxiety symptoms (PHQ-8/GAD-7 >= 10). Survey-weighted modified Poisson models estimated prevalence ratios (PRs), with interaction, sensitivity, and post …

Mapping The Uk Commercial Fishing Network: A Knowledge-Based Framework For Sustainable Technology Adoption And Environmental Decision-Making, Matthew Prowse

School of Engineering, Computing and Mathematics Theses

The UK commercial fishing industry operates within a complex web of stakeholders, technologies, and environmental pressures that challenge traditional approaches to sustainability and resource management. This research develops a comprehensive framework for understanding how technological advancement in UK fisheries creates unintended consequences that threaten long-term sustainability. Through a mixed-methods approach combining PESTLE analysis, grounded theory methodology, stakeholder mapping, case study investigation, this study introduces the "By-Product and Excess" theoretical framework to explain how fishing technologies generate two critical outcomes: by-products (undesirable environmental impacts such as CO₂ emissions, microplastics, and ecosystem damage) and excess (enhanced capacity to harvest beyond sustainable limits).The …

Investigating The Biocompatibility Of Nanosilver Hydroxyapatite Coatings With Human Gingival Fibroblasts To Enhance Abutment Integrity For Periodontal Health, Sian Morgan

School of Engineering, Computing and Mathematics Theses

Dental implants are susceptible to bacterial colonisation, which can initiate peri-implant inflammation and ultimately lead to peri-implantitis and implant failure. Antimicrobial surface modifications represent a promising strategy to mitigate bacterial infection however, such approaches must preserve biocompatibility with peri-implant soft tissue cells to ensure effective mucosal sealing and long-term implant success. In particular, human gingival fibroblasts (HGFs) play a critical role in soft tissue integration at the implant-abutment interface, yet their interactions with antimicrobial silver-based coatings remain insufficiently understood. This thesis investigates the biocompatibility of nano silver-hydroxyapatite (Ag+nHA) coatings deposited on titanium substrates, with the aim of developing an antimicrobial …

A General Tool To Assist With On Orbit Manufacturing, Richard Arundal

School of Engineering, Computing and Mathematics Theses

On-Orbit Manufacturing (OOM) presents a transformative paradigm in space mission design, enabling the in-situ production of components, tools, and large-scale structures beyond terrestrial constraints. This dissertation investigates the feasibility of OOM missions by developing a modular, iterative algorithm to support early-stage mission design and scenario analysis. The central hypothesis is that such an algorithm can be parameterised to evaluate a wide spectrum of manufacturing cases in space, ranging from small utility items to large structural systems.The research pursues four core objectives: assessing the terrestrial manufacturing lifecycle and its applicability in the space environment; identifying candidate manufacturing techniques suitable for orbital …

Bovine Lactoferrin Maintains Antibacterial Effect Against Neonatal Escherichia Coli Septicaemia Isolates Despite The Presence Of Iron Acquisition Genes, Matthew Mayorga, Joshua L. Wheatley, Brianna N. Maldonado, Susana Chavez-Bueno

Student Publications

Introduction. Escherichia coli is a dominant cause of neonatal sepsis for which no prevention measures currently exist. Lactoferrin (LF) is an iron-sequestering antibacterial protein that has been noticed to decrease neonatal late-onset sepsis.

Hypothesis/Gap Statement. LF’s effect on in vitro growth of neonatal E. coli clinical isolates causing septicaemia is unknown. The prevalence of iron acquisition virulence genes which contribute to pathogenicity outcomes in these strains has also not been described in detail.

Aim. To evaluate bovine lactoferrin’s (bLF) effects on the in vitro growth of neonatal septicaemia E. coli isolates, and to determine the presence of iron acquisition …

Highly Effective Combination Of Brg1/Brm Inhibitor With Bet Inhibitor Or Decitabine For High-Risk Mecom-Rearranged Aml, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, John A Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Jian Wang, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Ruud Delwel, Kapil N Bhalla

Faculty, Staff and Students Publications

In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. EVI1 is a transcriptional regulator that plays a role in proliferation and maintenance of a stem cell-like phenotype in AML. BRG1 (SMARCA4) and BRM (SMARCA2) are the mutually exclusive ATPases of the BAF (BRG1/BRM-associated factor) chromatin remodeling complexes. They regulate access to enhancers/promoters and gene-expressions orchestrating AML stem/progenitor cell proliferation and differentiation. AML with 3q26.2 rearrangements are clinically challenging and prognosis remains very poor. FHD-286 is an orally bioavailable, selective inhibitor of BRG1/BRM under clinical development in AML. Present studies …

School-Level Gaps In Mmr Coverage As The Fuel For Measles Outbreaks, Meagan C Fitzpatrick, Chad R Wells, Abhishek Pandey, Lamia Ayaz, Peter J Hotez, Seyed M Moghadas, Alison P Galvani

Faculty, Staff and Students Publications

No abstract provided.

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Long Covid And Cardiovascular Diseases Among U.S. Adults: Results From The U.S. Medical Expenditure Panel Survey, Geoffrey Y Zhang, John C Lin, Dang Nguyen, Sameed Ahmed M Khatana, Thomas P Giordano

Faculty, Staff and Students Publications

Objective: Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear.

Methods: Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses.

Results: Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR …

Ptpn1 Regulation Via Ybx1-Ptbp1 Interaction Promotes Fibroblast Activation And Fibrotic Remodeling In The Lung, Huibing Liu, Cong Xia, Yingying Zhang, Yulong Gan, Lianhui Cheng, Xuqian Wang, Airu Chang, Wenyu Zhao, Bin Li, Yaxuan Wang, Yajun Li, Ivan Rosas, Juntang Yang, Guoying Yu, Lan Wang

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology. Its pathogenesis involves complex multicellular interactions and signaling pathways, with fibroblast-to-myofibroblast transition (FMT) being critical for fibrogenesis. Although the transcription factor Y-box binding protein 1 (YBX1) regulates processes such as cell proliferation, transcription, translation, and DNA repair, its role in IPF remains undefined. Here, we demonstrate that YBX1 overexpression significantly promotes transforming growth factor-β1 (TGF-β1)-induced pulmonary FMT, leading to substantially increased extracellular matrix (ECM) deposition in primary human (PHLFs) and mouse (PMLFs) lung fibroblasts. Conversely, YBX1 inhibition markedly suppresses TGF-β1-driven aberrant fibroblast migration and activation. Mechanistically, YBX1 …

Molecular Heterogeneity Of Hpv-Associated Cancers And Strategies To Overcome Treatment Resistance, Sara Rasouli, Weiyi Gong, Raegan Wood, Danyal Daneshdoust, Anam Khan, Rani Mahyoob, Chongwen Cao, Zihao Yu, Nagireddy Putluri, Gennady Shvets, Haichang Li, Bo Zhao, Xuefeng Liu, Jenny Li

Faculty, Staff and Students Publications

Human papillomavirus (HPV) is a major driver of global cancer incidence, responsible for nearly all cervical cancers and a significant proportion of oropharyngeal, anal, and other anogenital cancers. Despite the availability of effective vaccines, HPV-associated cancers persist due to persistent infection, immune evasion, and the virus's ability to integrate into the host genome, contributing to molecular heterogeneity and therapeutic resistance. Here, we summarize molecular heterogeneity and the emerging combined therapeutic strategies. High-risk HPV types, notably HPV16 and HPV18, initiate carcinogenesis through persistent infection of epithelial basal cells and through the actions of the E6 and E7 oncoproteins, which disrupt the …

Investigating Food-Related Behaviors In Smith-Magenis Syndrome: Tailoring A Questionnaire For A Rare Disease, Citrine Elatrash, Theresa A Wilson, Alexis C Wood, Sarah H Elsea, Stephanie Sisley

Faculty, Staff and Students Publications

Purpose: Accurate measurement is essential for tracking changes in clinical outcomes. Individuals with Smith-Magenis syndrome (SMS) exhibit challenging and unique food-related behaviors. We sought to determine the best tool to capture their unique food-related behaviors.

Methods: We conducted focus groups with caregivers of individuals with SMS to evaluate two commonly used questionnaires for food-related behaviors- the Food Related Problems Questionnaire (FRPQ) and the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Based on caregiver input and clinical expertise, we adapted these existing measures into a new tool: the SMS-FRPQ. We then validated this instrument for internal consistency and concurrent validity using online …

Acmg Medical Directors’ Special Interest Group Survey: Current Challenges For Medical Genetics Clinics, Mark Dulchavsky, Catherine E Keegan, Nathaniel H Robin, Chad Haldeman-Englert, Shweta U Dhar, Fuki M Hisama

Faculty, Staff and Students Publications

Purpose: The American College of Medical Genetics and Genomics Medical Directors' Special Interest Group (SIG) began in 2021 as a forum for directors of medical genetics clinical groups to share questions, concerns, current practices, and solutions regarding clinical operations. We report on the first 4 years of the SIG-its membership growth and SIG activities. We also present quantitative and qualitative results of a nationwide survey of 66 SIG members addressing recurrent questions from members regarding: wait times, volume of referrals, clinical workload expectations, and independent practice of genetic counselors (GCs) and advanced practice providers.

Methods: Cross-sectional survey of American College …

Latent Factor Modeling Reveals Unexpected Spatial Heterogeneity In Human Alzheimer's Disease Brain Transcriptomes, Rami Al-Ouran, Chaozhong Liu, Linhua Wang, Zhijian Yu, Ying-Wooi Wan, Chaohao Gu, Xiqi Li, Gerarda Cappuccio, Mirjana Maletic-Savatic, Aleksandar Milosavljevic, Joshua M Shulman, Hu Chen, Zhandong Liu

Faculty, Staff and Students Publications

Alzheimer's disease is characterized by complex molecular and cellular heterogeneity, which complicates efforts to identify consistent biomarkers and therapeutic targets. To better characterize the heterogeneity, we applied latent factor modeling to RNA sequencing data from approximately 2,500 human Alzheimer's disease brain samples, uncovering underlying patterns in gene expression. These transcriptional groups demonstrated unique gene expression profiles related to synaptic and neuronal pathways, vasculature development, and protein folding and antigen processing. Notably, this latent factor reflects variation in spatial sampling. Adjusting for the latent factor improved the identification of differentially expressed genes in disease samples. This finding suggests that spatial heterogeneity …

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …