Medicine and Health Sciences Commons^™

Cardiometabolic And Molecular Adaptations To 6-Month Intermittent Fasting In Middle-Aged Men And Women With Overweight: Secondary Outcomes Of A Randomized Controlled Trial, Ruteja A Barve, Nicola Veronese, Beatrice Bertozzi, Valeria Tosti, Maria Lastra Cagigas, Francesco Spelta, Edda Cava, Laura Piccio, Dayna S Early, Richard D Head, Luigi Fontana

2020-Current year OA Pubs

Intermittent fasting (IF) has gained attention as a potential intervention for cardiometabolic health, though its long-term effects remain unclear. In this randomized clinical trial, we assessed the impact of 6 months of IF on body composition, cardiovascular risk factors, and related molecular pathways in middle-aged (30-65 years) men and women with overweight (BMI 24.8-35 kg/m²). In this trial, 41 participants were randomized to either an intermittent fasting (IF) intervention or to maintain their habitual diet. The primary outcome (circulating CRP concentration) was previously reported; here, we present exploratory analyses focusing on metabolomic and transcriptomic responses. IF led to an 8% …

In The Mouth Or In The Gut? Innovation Through Implementing Oral And Gastrointestinal Health Science In Chronic Pain Management, Jo Nijs, Burel R Goodin, Et Al.

2020-Current year OA Pubs

Recent scientific advances point towards an important role for oral and gastrointestinal health in people with chronic pain. Poor oral health (e.g., periodontitis, tooth loss) is observed in subgroups of the chronic pain population, including abdominal pain, low back pain, fibromyalgia, and rheumatoid arthritis. In addition to poor oral health, studies have also revealed altered intestinal microbiota compositions in various types of chronic pain, including people with chronic low back pain, knee osteoarthritis, visceral pain, fibromyalgia, tinnitus, and migraine. While overweight/obesity contributes to the likelihood of gut dysbiosis, normal-weight individuals with chronic pain also more often present with poor gut …

A Qualitative Exploration Of Patient And Clinician Needs And Preferences For A Physical Activity Intervention During Breast Cancer Chemotherapy, D Carolina Andrade, Loni Parrish, Courtney Harriss, Lindsay L Peterson, Ryan P Duncan, Jingqin Luo, Maura M Kepper, Christine Marx, Mary C Politi, Elizabeth A Salerno

2020-Current year OA Pubs

BACKGROUND: Early intervention with physical activity (PA) during active cancer treatment is critical for improved health outcomes, but often difficult to deliver. We assessed patients' and clinicians' needs and preferences for a PA intervention during chemotherapy via semi-structured interviews.

METHODS: We conducted virtual semi-structured interviews from May 2022 to May 2023 with patients with stage I-III breast cancer and oncology clinicians recruited from a Midwestern comprehensive cancer center and community settings. We identified themes using deductive and inductive thematic analysis informed by the Consolidated Framework for Implementation Research.

RESULTS: Patients (n = 16) were mostly White, non-Hispanic (93.8%) females (100%) …

Pharmacy Deserts And Health Inequities In St. Louis City: A Geospatial Analysis Of Access Disparities And Determinants, Antoine Brantley, Dominic Mosha, Bobie Williams, Quinn J Hill, Shontae Fluelen, Marcus Howard, Elvin Geng, Matifadza Hlatshwayo-Davis

2020-Current year OA Pubs

BACKGROUND: Pharmacy deserts, or areas lacking convenient access to pharmacies, can limit access to medications and reduce adherence. In U.S. cities, pharmacy deserts are disproportionately concentrated in racial/ethnic minority and low-income neighborhoods. This study examined the demographics and spatial distribution of pharmacy deserts in St. Louis City, Missouri, and their associations with sociodemographic and healthcare access determinants.

METHODS: Pharmacy deserts were defined as census tract block groups whose centroids were more than 1 mile from a pharmacy, or more than a half mile and located within a tract where at least 20% of households lacked vehicle access. Demographic and socioeconomic …

Evolutionarily Convergent Mechanism Of Formin Regulation Coordinates Actin Polymerization In Apicomplexan Parasites, Pengge Qian, Yong Fu, Jianwei Zeng, Michael J Naldrett, Rui Zhang, L David Sibley

2020-Current year OA Pubs

Apicomplexan parasites rely on actin-based motility for host cell invasion and for their dissemination. Although previous studies implicate formin 1 (FRM1) in governing this process in

Conservation Of Cis-Regulatory Codes Over Half A Billion Years Of Evolution, Yohey Ogawa, Yu Liu, Connie A Myers, Ala Morshedian, Gordon L Fain, Alapakkam P Sampath, Joseph C Corbo

2020-Current year OA Pubs

Identifying homologous cell types across species is essential for understanding cell type evolution. The retina is ideal for comparative analysis because its six major cell classes have persisted since the origin of vertebrates more than half a billion years ago. Here, we show that the retina's conserved cellular architecture is mirrored by deep conservation of the cis-regulatory codes that govern gene expression. Through single-cell chromatin accessibility analysis of lamprey, fish, bird, and mammalian retinas, we demonstrate cross-species conservation of cis-regulatory codes in all retinal cell classes despite extensive turnover of cis-regulatory regions. Conservation manifests as clustering of high-affinity transcription factor …

Acceptability, Appropriateness, Willingness To Use, And Perceptions Towards Hiv Self-Testing Among Adolescent Girls And Young Women In Rural Northern Uganda: A Baseline Formative Cross-Sectional Study, Ronald Olum, Morrish Obol Okello, Freddy Eric Kitutu, Elvin H Geng, Philippa Musoke

2020-Current year OA Pubs

BACKGROUND: Adolescent girls and young women (AGYW) in Uganda are at higher risk for and bear a significant HIV burden, accounting for 25% of new infections. Despite improved HIV testing services, AGYW in rural areas face barriers to facility-based testing due to stigma, physical access barriers, and confidentiality concerns. This study assessed the acceptability, appropriateness, willingness to use, and perceptions of HIVST among AGYW in Northern Uganda.

METHODS: This cross-sectional study was part of a baseline assessment for a quasi-experimental trial evaluating community-led HIVST among AGYW aged 15-24 years in 5 sub-counties in Omoro District. Data were collected using systematic …

Effect Of Same-Day Hiv Treatment Initiation (Sdi) On 1-Year Outcomes In Low-And Middle -Income Countries: Systematic Review And Meta-Analysis Of Randomised Trials, Nikita Sass, Hanna Havrylenko, Felix Gerber, Alain Amstutz, Sydney Rosen, Alana Brennan, Mhairi Maskew, Serena Koenig, Nancy Dorvil, Elvin H Geng, Tracy Glass, Nathan P Ford, Niklaus Daniel Labhardt, Stefan Schandelmaier

2020-Current year OA Pubs

INTRODUCTION: Same-day initiation (SDI) of antiretroviral therapy is recommended for people presenting with HIV who have no contraindications. We reviewed the evidence on SDI interventions in low- and middle-income countries (LMICs).

METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials of SDI in adults diagnosed with HIV in LMICs. We searched MEDLINE, Embase and the Cochrane Library up to December 2024. Primary outcomes were viral suppression and retention in care 6-12 months after enrolment. Based on a qualitative assessment of the complex trial interventions, we considered two subgroups: (1) interventions newly introducing SDI and (2) interventions improving …

Nktr-255 Enhances Complete Response Following Cd19 Car T-Cell Therapy In Patients With Relapsed/Refractory Large B-Cell Lymphoma, Sairah Ahmed, John Dipersio, Et Al.

2020-Current year OA Pubs

No abstract provided.

Deep Profiling Of Human T Cells Defines Compartmentalized Clones And Phenotypic Trajectories Across Blood And Tonsils, Suhas Sureshchandra, Elizabeth Levendosky, Allyssa Daugherty, Samuel J H Murphy, Chandrani Thakur, Naresha Saligrama, Et Al.

2020-Current year OA Pubs

98% of T cells reside in tissues, yet nearly all human T cell analyses are performed on peripheral blood. We performed single-cell sequencing of 5.7 million T cells from autologous blood and tonsils of ten donors. We identified distinct patterns of clonal expansion associated with tonsil-restricted phenotypes. Clonal sharing between blood and tonsils was lower than previous estimates and increased with age. Identical T cell receptor (TCR) sequences exhibited limited concordance in their phenotypes across compartments. Furthermore, location dictated the frequencies, clonal dominance, and phenotypes of antigen-specific T cells. Using immune organoids, we showed that antigen exposure drives functionally distinct …

Biological Parenthood Rates Among Men With Sickle Cell Disease, Anyssa N Young, Sarah R Hayford, Sapuni S Chandrasena, Sara Conroy, Tanvi P Karkare, Barbara L Kroner, Allison King, Robert M Cronin, Luca Badolato, Leena Nahata, Susan E Creary

2020-Current year OA Pubs

No abstract provided.

Glycoside Hydrolase-Mediated Glucomannan Catabolism In Segatella Copri, A Target Of Microbiota-Directed Foods For Malnourished Children, Cyrus Zhou, Matthew C Hibberd, Evan M Lee, Suzanne Henrissat, Marie A Crane, Jiye Cheng, Michael J Barratt, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of

Association Of Pet4 Response With Outcomes Of Bv-Chp Vs Chop In The Echelon-2 Trial In Cd30+ Peripheral T-Cell Lymphoma, Swaminathan Iyer, Neha Mehta-Shah, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

In the phase 3 ECHELON-2 trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV-CHP) significantly improved progression-free survival (PFS) and overall survival (OS) compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with CD30+ peripheral T-cell lymphoma, benefits that were maintained at 5 years. Interim positron emission tomography (PET) scan can be used to assess prognosis and risk-stratify patients. The prognostic value of interim PET was assessed in this post hoc exploratory analysis from ECHELON-2, evaluating interim 18F-fluorodeoxyglucose PET scans after cycle 4 (PET4) and end-of-treatment-based response, and correlated with PFS per investigator and OS. PET4 response was determined by …

Myocardial Lipin1 Protects The Heart Against Ischemic Injury By Preserving Lipid Homeostasis, Jiaxi Guo, Brian N. Finck, Et Al.

2020-Current year OA Pubs

Impaired cardiac lipid metabolism has been reported to cause heart failure. Lipin1, a multifunctional protein, is a phosphatidate phosphatase that generates diacylglycerol from phosphatidic acid and a transcriptional cofactor that regulates lipid metabolism-related gene expression. Here, we investigated the roles of lipin1 in cardiac remodeling after myocardial infarction (MI). The expression levels of lipin1 significantly decreased in cardiomyocytes of the human failing heart and murine ischemic myocardium. Cardiomyocyte-specific Lpin1 knockout (cKO) mice showed left ventricle enlargement and reduced fractional shortening after MI, compared with control mice. This was accompanied by elevated cardiac fibrosis, accumulation of reactive oxygen species, and increased …

Liver Injury In A Preclinical Model Of Short Bowel Syndrome Is Associated With Impaired Autophagy, Daniel M Alligood, Alex Park, Kerry Swanson, Naima Pyarali, Evan Mayse, David M Alvarado, Xiuli Liu, Jae-Sung Kim, Nicholas O Davidson, Deborah C Rubin, Jun Guo, Brad W Warner

2020-Current year OA Pubs

Critical for cellular maintenance and repair, autophagy recycles damaged or redundant cellular components. Dysregulated autophagy is associated with progressive cellular injury in various liver pathologies. However, the role of autophagy in intestinal failure-associated liver disease has not previously been investigated. Using a preclinical murine model of short bowel syndrome, we explored the role of autophagy impairment at early and late time points. Regardless of sex, small bowel resected (SBR) mice demonstrated significant liver injury compared to sham controls, exhibiting elevated serum transaminases, altered liver histology, and increased mRNA expression of endoplasmic reticulum stress marker (Ddit3) and oxidative stress marker (Nqo1). …

Insm1 Governs A Neuronal Progenitor State That Drives Glioblastoma In A Human Stem Cell Model, Patrick A Desouza, Matthew Ishahak, Xuan Qu, Colin Mccornack, Devi Annamalai, Diane D Mao, Rajanikanth Vangipurapu, Yiwei Fu, Alexandre T Vessoni, Ryan T Cleary, Rowland H Han, Punn Augsornworawat, Timothy Woodiwiss, Darby Agovino, Braxton Sizemore, Jessica Kline, Maryam Borhani-Haghighi, Hao Chen, Sangami Pugazenthi, Hiroko Yano, Ting Wang, Luis F Z Batista, Jeffrey R Millman, Albert H Kim

2020-Current year OA Pubs

Glioblastoma is a lethal brain cancer marked by functional plasticity driven by tumor cell-intrinsic mutations and their interplay with developmental programs. To investigate how canonical glioblastoma mutations promote functional plasticity, we have developed an isogenic human neural stem cell (NSC) model of glioblastoma by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increases TERT expression during serial mutagenesis, but only triple mutant NSCs reliably form lethal brain tumors in vivo that recapitulate glioblastoma. Tumor cell evolution triggers stress-related metabolic changes and transitions toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed …

Synergistic Potential Of Sipuleucel-T In Enhancing Immunotherapy For Metastatic Castration-Resistant Prostate Cancer, Kavita Rawat, Varnika Punia, Parker Mathews, Sara Mccoy, Wilbur Song, Muhammad A Saeed, Russell K Pachynski

2020-Current year OA Pubs

Clinical trials of immunotherapy in metastatic castration-resistant prostate cancer (mCRPC) have largely been unsuccessful despite promising preclinical studies and proven efficacy in other solid tumors. These disappointing clinical outcomes have been attributed to an immunosuppressive tumor microenvironment, a relative lack of infiltrating immune effector cells, and tumor-related and host-related factors, which collectively render prostate cancer a relatively immunologically "cold" tumor. Sipuleucel-T (Provenge), an autologous cellular immunotherapy, induces an immune response targeted against prostatic acid phosphatase. It received approval from the US Food and Drug Administration in 2010, marking the first immunotherapy to show an overall survival benefit in patients with …

Patient-Centered Televisit For Chronic Obstructive Pulmonary Disease Discharge Transitions: User-Centered Design Study, Joanna Abraham, Alicia Meng, Nicolas Caravelli, Leah Traeger, May Nguyen, Vineet Arora, Valerie G Press

2020-Current year OA Pubs

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects approximately 16 million Americans and often results in avoidable readmissions due, in part, to medication errors and lack of education. Telehealth interventions can support medication reconciliation and inhaler education following hospital discharge for patients with COPD.

OBJECTIVE: This study aimed to design and prototype TELE-TOC (Telehealth Education: Leveraging Electronic Transitions of Care), a post-discharge, in-home, televisit intervention, and to map its workflow to ensure integration into the routine discharge care transition process for patients with COPD.

METHODS: A user-centered design approach across 3 phases was followed to develop and prototype TELE-TOC. Participants included …

Functional Classification Of Platelet Gene Variants Using Crispr Hdr In Cd34+ Cell-Derived Megakaryocytes, Yasuhiro Kosaka, Brandon Lopez, Nina Kishimoto, Shancy Jacob, Emilie Montenont, Rodrigo Huallanca, Graeson Coughenour, Jorge Di Paola, Justyne Ross, Kristy Lee, Matthew T Rondina, Paul F Bray, Jesse W Rowley

2020-Current year OA Pubs

The interpretation of genetic variants in inherited diseases, such as inherited platelet disorders (IPDs), remains a major clinical challenge, as most are classified as variants of uncertain significance (VUSs). A key barrier to functional evaluation is the lack of accessible, lineage-appropriate assays that reliably reflect native gene regulation and cell-specific biology. To address this gap, we developed CRIMSON HD (CRISPR-edited megakaryocytes [MKs] for surveying platelet variant functions through homology-directed repair [HDR]), a CRISPR-Cas9 HDR-based genome-editing platform applicable to CD34

Brain Metabolic-Functional (De)Coupling From Health To Glioma Dysfunction, G Vallini, G Baron, E Silvestri, T Volpi, A G Vlassenko, M S Goyal, A Chiuso, D Cecchin, M Corbetta, A Bertoldo

2020-Current year OA Pubs

The interplay between brain metabolism and function supports the brain's adaptive capacity in cognitively demanding processes. Prior work has linked glucose metabolism to resting-state fMRI activity, but often overlooks both hemodynamic confounders in the BOLD signal and the brain's dynamic nature. To address this, we employed a novel effective connectivity decomposition, separating symmetric partial covariance, capturing "true" statistical dependencies between regions, from antisymmetric differential covariance, reflecting directional brain flow. In 42 healthy subjects, we show that partial covariance corresponds to metabolic connectivity across regions, while node directionality relates to standardized uptake value ratio, a proxy for local glucose consumption. We …

Optimizing Clinical Monitoring And Management Guidelines For Capivasertib In Hr-Positive/Her2-Negative Advanced Breast Cancer: Expert Opinion, Neil M Iyengar, Joyce A O'Shaughnessy, Heather N Moore, Erika Hamilton, Komal L Jhaveri, Cynthia X Ma, Karen Tedesco, Monali Vasekar, Sarah Donahue, Hope S Rugo

2020-Current year OA Pubs

Capivasertib, an AKT inhibitor, approved in combination with fulvestrant for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with ≥1 PIK3CA, AKT1, and/or PTEN alterations, significantly improved progression-free survival in the CAPItello-291 phase 3 trial. However, capivasertib-associated adverse events of diarrhea, rash, and hyperglycemia may require proactive management. This article provides practical recommendations to support prevention and early intervention to optimize adherence and treatment outcomes.

Enhancing Intergenerational Health In Nigeria: Peripartum As Critical Life Stage For Cardiovascular Health (Enhance-Cvh) Study: Findings From Pre-Implementation Using The Updated Consolidated Framework For Implementation Research (Cfir 2.0), Julia D López, Cecilia Nartey, Debra Haire-Joshu, Victor G Dávila-Román, Mark D Huffman, Clementina E Okoro, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pregnancy is a crucial period to improve cardiovascular health (CVH) for mothers and their families. The current study emphasizes framework-guided factors that influence the adaptation of an evidence-based intervention (Parents as Teachers and Healthy Eating Active Living Taught at Home [PAT + HEALTH]) to support healthy gestational weight gain and postpartum weight management among pregnant women with obesity and their infants in Nigeria.

METHODS: From May to June 2023, 43 in-depth interviews were conducted with 11 parents, 15 community health extension workers (CHEWs)/health educators, and 17 policymakers/ healthcare supervisors in the Federal Capital Territory, Nigeria. Additionally, nine focus groups …

Comparing Isocitrate Dehydrogenase Inhibitors With Procarbazine, Lomustine, And Vincristine Chemotherapy For Oligodendrogliomas, Gerardo Duran, Diego Pichardo-Rojas, Ahmed Hashim Ali, Peter Passias, Angela Downes, Wilson Z Ray, Gregory J Zipfel, Hakeem J Shakir, Andrew Bauer, Andrew Jea, Ian F Dunn, Jeffrey A Zuccato, Christopher S Graffeo, M Burhan Janjua

2020-Current year OA Pubs

The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA.

Operationalizing Passive Sensors Into Scalable, Reproducible, Neurobehavioral Digital Markers For Alzheimer's Disease: Lessons Learned Over 10 Years, Ganesh M Babulal, Matthew Blake, Chen Chen, Yiqi Zhu, Subrata Pal, David C Brown

2020-Current year OA Pubs

No abstract provided.

Proposed Medical School Curricula For 3d Printing, Danielle Heiser, David H Ballard, Et Al.

2020-Current year OA Pubs

BACKGROUND: 3D printing is increasingly utilized in medical education, providing a hands-on approach to anatomical learning, surgical planning, and interdisciplinary collaboration. Despite growing interest, standardized curricula incorporating 3D printing into medical education are lacking.

METHODS: A multidisciplinary team of medical educators, engineers, and students developed three distinct curricular models to integrate 3D printing into undergraduate medical education. These models include (1) integration into anatomy coursework, (2) a fourth-year clerkship elective, and (3) a pre-clerkship elective. The outline for each curriculum was designed to be adaptable across institutions, emphasizing hands-on learning, imaging segmentation, basic elements of computer-aided design (CAD), and 3D …

Statistically Significant Association Does Not Imply Improvement In Prediction Of Clinical Outcomes, Shu Jiang, Bernard A Rosner, Graham A Colditz

2020-Current year OA Pubs

UNLABELLED: In the current landscape of clinical studies, the concept of statistically significant association is often mixed up with the expectation of improved prediction performance. We discuss the two concepts, association and prediction, and present the epidemiologic principles and statistical constructs that underlie the discrepancy between statistically significant associations and the rationale for their lack of impact on improving prediction in terms of discrimination. This issue is illustrated using an existing breast cancer dataset. The concept of statistically significant association should not be mixed up with the expectation of improved discrimination performance. Although some markers may not markedly improve discrimination, …

Using Gnotobiotic Mice To Decipher Effects Of Gut Microbiome Repair In Undernourished Children On Tuft And Goblet Cell Function, Yi Wang, Hao-Wei Chang, Jiye Cheng, Daniel M Webber, Hannah M Lynn, Matthew C Hibberd, Clara Kao, Ishita Mostafa, Tahmeed Ahmed, Michael J Barratt, Jeffrey I Gordon

2020-Current year OA Pubs

Studies have implicated perturbations in the postnatal development of the gut microbiome as a contributing factor to childhood undernutrition. Compared to a standard ready-to-use supplementary food, a microbiome-directed complementary food (MDCF-2) designed to repair these perturbations produced superior improvements in ponderal and linear growth in clinical trials of Bangladeshi children with moderate acute malnutrition. Here, "reverse translation" experiments are performed where intact fecal microbiomes collected from trial participants before and at the end of treatment are introduced into female gnotobiotic mice just after delivery of their pups. Pups received diets designed to resemble those consumed by children in the trials …

Fucosylated N-Glycan Landscape Of Triple-Negative Breast Cancer, Danielle A Scott, Souvik Seal, Laura Spruill, Jaclyn Dunne, Graham Colditz, Anand S Mehta, Richard R Drake, Marvella E Ford, Peggi M Angel

2020-Current year OA Pubs

UNLABELLED: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapies. Although aberrant N-glycosylation is a hallmark of malignancy, the specific roles of core-fucosylated (CF) and outer arm-fucosylated (OAF) N-glycans in TNBC progression and patient survival remain underexplored. This study utilized multiplexed glycomics by matrix-assisted laser desorption/ionization imaging mass spectrometry to spatially profile 348 N-glycans in 59 TNBC tumors with clinical characteristics including survival data. Spatial analysis revealed distinct localization patterns of CF and OAF isomers within tumor microenvironments. Strikingly, OAF glycans, but not CF, were strongly associated with tumor stage, with expression increasing from stage …

A Multi-Center Retrospective Cohort Study Of Neurosarcoidosis Myelitis: Current Observations And Future Directions, Giovanna S Manzano, David B Clifford, Steven Richard Dunham, Masoud Majed, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales.

METHODS: Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post-contrast gadolinium enhancement resolution at 6 months post-treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow-up.

RESULTS: Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39-55); male: female 1.3:1). Median nadir mRS and …

Functional Connectivity Associations With Markers Of Disease Progression In Grn Pathogenic Variant Carriers, Taru M Flagan, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant progranulin (GRN) pathogenic variants are a genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that asymptomatic GRN variant carriers exhibit thalamocortical hyperconnectivity that increases with age, presumably as they are approaching symptom onset. Whether hyperconnectivity arises concomitantly with markers of neurodegeneration remains unclear.

METHODS: Utilizing T1 and task-free functional magnetic resonance imaging from 49 asymptomatic and 26 symptomatic GRN variant carriers, we determined the relationships between functional connectivity, as measured by voxelwise …