Digital Commons Network^™

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Sex-Related Variability In The Perception Of Symptoms Associated With Common Otolaryngologic Complaints, Sabrina K Wagner, Jakob L Fischer, Alvaro Navarro, Lily Trinh, Waleed M Abuzeid, Ian M Humphreys, Nadeem A Akbar, Sharan Shah, Jivianne T Lee, Tara Wu, John S Schneider, Edward D Mccoul, Charles A Riley, Anthony M Tolisano

2020-Current year OA Pubs

OBJECTIVE: To assess the differences in the symptoms associated with common otolaryngology complaints between male and female patients.

METHODS: Between June 2020 and July 2023, a multi-institutional cross-sectional study was performed at six tertiary academic otolaryngology practices using semantics-based questionnaires to assess the symptoms patients associate with the complaints of sinus infection, reflux, congestion, and dizziness. Patients selected symptoms from lists of proposed terms to describe the various conditions. The primary outcome measure was sex-related differences in respondent symptom selection.

RESULTS: Four separate questionnaires were completed by a total of 1495 patients (46.0% male, 54.0% female). Female patients more often …

The Resilience Of The Human Lungs: Evolution, Smoke, And Disease, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Clostridioides (Clostridium) Difficile In Children And Adolescents In The Community In Cambodia, Lengsea Eng, Paul Turner, Kefyalew Addis Alene, Deirdre A. Collins, Su Chen Lim, Pisey Tan, Sona Soeng, Dylorng Hun, Sotera Yohn, Sarim Vong, Archie C.A. Clements, Thomas V. Riley

Research outputs 2022 to 2026

Background: Clostridioides (Clostridium) difficile transmission between community and healthcare settings has been increasingly reported. We aimed to identify the prevalence and molecular epidemiology of C. difficile colonising adolescents and non-hospitalised children in Cambodia. Methods: Stool samples were collected from 266 students at the University of Health Sciences (UHS) in Phnom Penh, between July and August 2022, and 246 children ≥1 year old visiting the outpatient department (OPD) at Angkor Hospital for Children in Siem Reap, between January and August 2022. C. difficile culture, toxin gene detection and PCR ribotyping were performed. Results: Overall, C. difficile was recovered from 07/266 specimens …

A Single Bout Of Resistance Or High-Intensity Interval Training Increases Anti-Cancer Myokines And Suppresses Cancer Cell Growth In Vitro In Survivors Of Breast Cancer, Francesco Bettariga, Dennis R. Taaffe, Cristina Crespo-Garcia, Timothy D. Clay, Mauro De Santi, Giulia Baldelli, Sanjeev Adhikari, Elin S. Gray, Daniel A. Galvão, Robert U. Newton

Research outputs 2022 to 2026

Purpose: Breast cancer is the leading cause of cancer-related death in women, highlighting the need for strategies to mitigate recurrence and mortality. We examined the effects of a single bout of resistance training (RT) versus high-intensity interval training (HIIT) on anti-cancer myokines and in vitro cancer cell suppression. Methods: Thirty-two survivors of breast cancer were randomly allocated to a single bout of RT (n = 16) or HIIT (n = 16). Blood was collected before, immediately post (0P) and 30 min post (30P) exercise. We measured serum levels of decorin, interleukin 6 (IL-6), secreted protein acidic and rich in cysteine …

Knowledge And Perceptions Of Modifiable Ischaemic Heart Disease Risk Among Indians: Scoping Review, Kunwar Kaur, Ma'en Zaid Abu-Qamar, Amineh Rashidi, Nilufeur Mckay, Rosemary Saunders

Research outputs 2022 to 2026

Background: Ischaemic heart disease (IHD) causes a significant number of deaths globally. India has the highest IHD burden, with cases up 138% since 1990. Individuals of Indian descent face a greater risk of early IHD and poorer long-term outcomes. Indian people typically develop IHD a decade earlier than other populations, with 52% of IHD-related deaths occurring before the age of 70, compared to 23% in Western populations. Aims: This review aims to synthesise evidence on the Indian population's knowledge and perceptions of modifiable IHD risk factors and identify literature gaps. Methods: Joanna Briggs Institute (JBI) methodology and the Preferred Reporting …

The Moderating Effect Of Dietary Patterns On The Association Of Depression And Anxiety With Cognitive Function, Hilal Salim Said Al Shamsi, Samantha L. Gardener, Hamid R. Sohrabi, Kevin Taddei, Colin L. Masters, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.B. Fernando

Research outputs 2022 to 2026

Background and aims: Investigating modifiable risk factors, such as diet, is crucial in understanding their effects on the relationship between Alzheimer's disease (AD)-related cognitive decline and related conditions. This study assesses whether dietary patterns moderate the relationship between symptoms of depression, anxiety, and cognitive function in older adults. Given that biological and psychosocial differences between sexes may influence dietary behaviours, mental health symptoms, and cognitive outcomes, conducting sex-stratified analyses will allow for identification of differential associations. Method: Cross-sectional data from cognitively unimpaired older adults (n = 1174, age ≥60 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were …

Rest-Activity Rhythm Phenotypes In Adults With Epilepsy And Intellectual Disability, Nandani Adhyapak, Grace E Cardenas, Mark A Abboud, Vaishnav Krishnan

Faculty, Staff and Students Publications

Objective: Rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe RAR perturbations in intellectually disabled adults with epilepsy ("E + ID"), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function, and/or comorbid psychopathology.

Methods: Caregivers of E + ID subjects provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers …

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

First Assembly Of A Draft Genome Of The Critically Endangered Northern Muriqui ( Brachyteles Hypoxanthus , Primates, Atelidae) Including Non‐Invasive Genotyping Strategies For The Species, Amanda Alves De Melo-Ximenes, Romina Batista, Leonardo Carlos Jeronimo Corvalán, Tomas Marques-Bonet, Lukas Kuderna, Kyle Farh, Jeffrey Rogers, Mariane Da Cruz Kaizer, Jean Philippe Boubli, Fabiano Rodrigues De Melo, Rhewter Nunes, Mariana Pires De Campos Telles

Faculty, Staff and Students Publications

Genomic resources, such as draft genomes, are vital for biodiversity monitoring and conservation. For endangered species, they enable the development of tools like organellar genomes and molecular markers, which are crucial for population genetics. Advances in sequencing technologies now allow high‐throughput genotyping with detailed amplicon sequences, enhancing genetic variation studies. The northern muriqui ( Brachyteles hypoxanthus ), a critically endangered primate endemic to Brazil's Atlantic Forest, currently lacks both nuclear and mitochondrial genome data and species‐specific microsatellite markers for population genetic studies. We assembled a 2.52 Gb draft genome for B. hypoxanthus with 202,243 contigs (N50 = 29,134 bp), and …

Insights Into The Molecular Mechanism Of Pulmonary Vein Stenosis In Pediatric Patients With Congenital Heart Disease, Alyssa B Kalustian, Pengfei Ji, Lalita Wadhwa, Christopher A Caldarone, Manish Bansal, Athar M Qureshi, Jeffrey S Heinle, Ravi K Birla

Faculty, Staff and Students Publications

Objective: Pediatric pulmonary vein stenosis (PVS) is associated with substantial morbidity and mortality for the subset of patients with recurrent or progressive disease. The molecular mechanisms underlying the development and trajectory of PVS remain unclear. This study characterizes the transcriptome of clinical and phenotypic subtypes of PVS.

Methods: Bulk RNA sequencing analysis was performed on human pulmonary vein tissue samples obtained from surgical interventions for pediatric patients with PVS. Transcriptomic profiles were compared for primary versus postrepair PVS as well as aggressive versus nonaggressive clinical phenotypes. Principal component analysis was performed, the differential gene expression quantified, and pathway analysis conducted …

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W Tomas, Jacklynn M Fitzgerald, C Lexi Baird, Courtney C Haswell, Chadi G Abdallah, Michael Angstadt, Justin T Baker, Hannah Berg, Jennifer U Blackford, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Terri A Deroon-Cassini, Seth G Disner, Wissam El Hage, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A Mclaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey

Faculty, Staff and Students Publications

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven …

Psychometric Evaluation Of The Yale-Brown Obsessive-Compulsive Scale In Pregnant Women, Catherine E Rast, Rashelle Musci, Jonathan S Abramowitz, Gerald Nestadt, Paul Nestadt, Mary C Kimmel, Tracey Dibbs, Lauren M Osborne, Jack Samuels, Janice Krasnow, Eric A Storch

Faculty, Staff and Students Publications

Purpose: Although many women experience obsessive-compulsive symptoms during the perinatal period, the Yale-Brown Obsessive Compulsive Scale (YBOCS) has not yet been psychometrically evaluated in this population. This study examined the internal consistency, convergent and divergent validity, and factor structure of the YBOCS among pregnant women.

Methods: 256 Women who were 20 to 24 weeks pregnant completed the clinician-administered YBOCS and Mini International Neuropsychiatric Interview (MINI) along with a series of self-report questionnaires including the Edinburgh Postnatal Depression Scale (EPDS), Perinatal Anxiety Screening Scale (PASS) and Obsessive-Compulsive Inventory-Revised (OCI-R).

Results: Internal consistency of the YBOCS was excellent, and there were strong …

Temporal Disparities In Diagnosis: The Critical Impact Of Laboratory Workflow Inefficiencies On Outcomes In Metabolic And Cardiovascular Disorders, Evans Dzreke, Celene Dzreke, Ramseyer Adekorang Asamoah, David Kanze

Health & Biomedical Sciences Faculty Publications

Diagnostic delays and laboratory process inefficiencies constitute a common but unaddressed dilemma in contemporary healthcare, quietly undermining patient outcomes in metabolic and cardiovascular illnesses where immediate intervention is critical. This seminal work goes beyond traditional operational viewpoints to demonstrate diagnostic inefficiency as an independent, adjustable risk factor with far-reaching implications. We rigorously quantified the impact of delayed test processing and reporting on clinical outcomes using a comprehensive mixed-methods approach that included multi-center retrospective cohort analysis (N=128,743 patients), real-time workflow mapping across 37 laboratories, in-depth case reviews, and economic modeling. Our findings challenged conventional wisdom by indicating that each 24-hour increase …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

The Effect Of Maternal Antioxidant Vitamin Supplementation On Maternal And Cord Blood Adiponectin Concentrations, Jessica L Pippen, Paula Mcgee, James M Roberts, Leslie Myatt, Michael W Varner, Alan T N Tita, Ronald J Wapner, John M Thorp, Brian M Mercer, Beth A Plunkett, Sean C Blackwell, Anthony Sciscione, George R Saade

Faculty, Staff and Student Publications

Adiponectin is a hormone that modulates glucose regulation and fatty acid oxidation. Low adiponectin concentration has been associated with increased insulin resistance. Studies show a beneficial effect of vitamin E supplementation on insulin sensitivity. We aimed to investigate the association of prenatal antioxidant supplementation with increased adiponectin concentrations in pregnant participants and their newborn infants.Secondary analysis of a randomized control trial of prenatal vitamin C and E supplementation to prevent preeclampsia in low-risk nulliparous participants. Plasma of participants at time of randomization (9-16 weeks gestation) and delivery, and neonatal cord blood were analyzed by specific enzyme-linked immunosorbent assay for adiponectin …

Associative Coding Of Conditioned Fear In The Thalamic Nucleus Reuniens In Rodents And Humans, Tuğçe Tuna, Michael S Totty, Muhammad Badarnee, Flávio Afonso Gonçalves Mourão, Shaun Peters, Mohammad R Milad, Stephen Maren

Faculty, Staff and Student Publications

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remain unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. …

The Importance Of Imperfect Pre-Clinical Models In Adolescent Idiopathic Scoliosis, Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, …

Fold-And-Fuse Neurulation In Zebrafish Requires Vangl2, Jacalyn Macgowan, Mara Cardenas, Margot Kossmann Williams

Faculty, Staff and Students Publications

Shaping of the future brain and spinal cord during neurulation is an essential component of early vertebrate development. In amniote embryos, primary neurulation occurs through a "fold-and-fuse" mechanism by which the edges of the neural plate fuse into the hollow neural tube. Failure of neural fold fusion results in neural tube defects (NTDs), which are among the most devastating and common congenital anomalies worldwide. Unlike amniotes, the zebrafish neural tube develops largely via formation of a solid neural keel that later cavitates to form a midline lumen. Although many aspects of primary neurulation are conserved in zebrafish, including neural fold …

Prevalence Of Fibrosis In Hepatic Explants And Biopsies From Individuals With Urea Cycle Disorders, Saima Ali, Aisha Nisar, Anqing Zhang, Sandesh Nagamani, Nathalie M Aceves-Ewing, Brandy Rawls, Thu Quan, Greg Enns, John Goss, Daniel H Leung, Benjamin L Shneider, Shilpa Jain, Florette K Hazard, Deborah Schady, Lindsay C Burrage

Faculty, Staff and Students Publications

Background: Various forms of liver disease have been increasingly reported in individuals with urea cycle disorders (UCDs). In this study, we performed the first systematic and standardized histopathological assessment of the prevalence of fibrosis and steatosis in a large sample of hepatic explants and biopsies from individuals with UCDs at two liver transplantation centers.

Methods: Sixty-seven hepatic tissue samples from 66 individuals with UCDs were staged by two pathologists for hepatic fibrosis and steatosis using standard scoring systems at two large liver transplantation centers in the United States. Histopathological findings were correlated with clinical parameters, including UCD type, laboratory parameters, …

Effective Algorithm To Differentiate Nbs Mcadd Cases From Carriers And Non-Carriers And An Assessment Of The Utility Of The Second Newborn Screen For Mcadd, Matthew T Snyder, Kristian Divin, Ning Liu, Qin Sun, Yue Wang, Xi Luo, Yishay Ben-Moshe, Lindsay C Burrage, V Reid Sutton

Faculty, Staff and Students Publications

False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS), with predominantly white, non-Hispanic subjects. Texas performs two NBSs and there is a majority Hispanic population in our region. This study aims to analyze biochemical and DNA data to more easily distinguish affected individuals from carriers or healthy non-carriers and identify benefits and challenges of a second NBS for MCADD. Biochemical and targeted DNA data from NBS dried blood …

Dissemination And Implementation Of A Telehealth-Enabled Program For Providing Infectious Disease Expertise In Rural Settings, Robin L P Jump, Jason P Burnham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Telehealth can facilitate improving antibiotic use and related antimicrobial stewardship activities in facilities underserved by infectious diseases (IDs) expertise. We describe implementation of the Department of Veterans Affairs (VA) videoconference antimicrobial stewardship team (VAST) to connect multidisciplinary teams from rural VA medical centers (VAMCs) with geographically distant ID experts.

METHODS: We implemented VASTs at 10 rural VAMCs from September 2021 to February 2024. VASTs consisted of regular meetings between rural VAMCs and an off-site ID expert who met by videoconference to discuss clinical cases, emphasizing recommendations for antibiotic prescribing. The VA Corporate Data Warehouse was used to collect information …

Semaphorin 3e-Plexin-D1 Pathway Downstream Of The Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, And Ovarian Angiogenesis In Mice, Hanxue Zhang, Jimmy Dhillon, Paul D Soloway, Bo Shui, Seoyeon Lee, Jennifer K Grenier, Paul R Munn, M Cecilia Ljungberg, Rebecca B Williams, Rainer B Lanz, Yu-Hsiang Liao, Yi A Ren

Faculty, Staff and Students Publications

Ovulation is induced by the luteinizing hormone (LH) surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Semaphorin 3E (Sema3E)-Plexin-D1 pathway regulates angiogenesis in other tissues, but its role in the ovary is unknown. Evidence indicates that Sema3E-Plexin-D1 pathway plays an important role in the mouse ovary. The expression of Sema3E and its receptor, Plexin-D1, is dynamically regulated in the mouse ovary downstream of the LH surge. This regulation requires the modulation of chromatin accessibility by CCAAT/enhancer-binding proteins α and β. Intraovarian injection of recombinant Sema3E results in reduced ovulation, impaired corpus luteum formation, and aberrant ovarian angiogenesis. These …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

Integrative Exome Sequencing And Machine Learning Identify Micb And Interferon Pathway Genes As Contributors To Ssc Risk, Shamika Ketkar, Hongzheng Dai, Lindsay Burrage, David Murdock, Brian Dawson, Marialbert Acosta-Herrera, Martin Kerick, Javier Martin, Kevin Wilhelm, Jennifer Kay Asmussen, Olivier Lichtarge, Regeneron Genetics Center, Shervin Assassi, Maureen D Mayes, Brendan H Lee

Faculty, Staff and Students Publications

Objectives: Systemic sclerosis (SSc) is a complex autoimmune disease with both known and unidentified genetic contributors. While genome-wide association studies (GWAS) have implicated multiple loci, many reside in noncoding regions. We aimed to identify novel protein-coding variants and pathogenic pathways using exome sequencing (ES) integrated with an Evolutionary Action-Machine Learning (EAML) framework, single-cell RNA sequencing (scRNA-seq), and expression quantitative trait locus (eQTL) analysis.

Methods: GWAS was conducted in 2,559 SSc cases and 893 controls of Caucasian ancestry, with replication in 9,846 cases and 18,333 controls of European ancestry. EAML prioritized genes with high-impact missense variants predictive of disease. Public scRNA-seq …

Autophagy Regulates Müller Glial Cell Inflammatory Activation, Teresa A Doggett, Zhenqing Zhou, Sohini Rebba, Jacqueline Unsinger, Philip A Ruzycki, Thomas A Ferguson

2020-Current year OA Pubs

PURPOSE: We tested whether Müller cells utilize autophagy to support immune privilege in the eye.

METHODS: The essential autophagy gene Atg5 was deleted in retinal Müller cells. Inflammation was induced by intravitreal injection of lipopolysaccharide (LPS) that was monitored by hematoxylin and eosin (H&E) staining, immunofluorescent confocal microscopy, and flow cytometry. Single-cell RNA sequencing was performed on retinal Müller cells isolated from control and Atg5-deficient mice. Markers of Müller cell gliosis were assessed, and cytokine production in the eye was measured. Small interfering RNA knockdown techniques were used to examine LPS-induced inflammatory pathways in culture.

RESULTS: We observed increased and …

High-Density Lipoprotein-Associated Cholesterol Abnormalities In A Clinical Outcomes Study Of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2, Zoe White, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limb-girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, DYSF. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.

METHODS: Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated …

Association Between Nt-Probnp Changes And Clinical Outcomes In Paediatric Patients With Heart Failure: Insights From Panorama-Hf And Paradigm-Hf, Robert Shaddy, Charles Canter, Et Al.

2020-Current year OA Pubs

AIMS: The PANORAMA-HF trial demonstrated significant N-terminal pro-B-type natriuretic peptide (NT-proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT-proBNP levels with clinical outcomes in PANORAMA-HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT-proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM-HF trial.

METHODS AND RESULTS: This post hoc analysis utilized data from Part 2 of the PANORAMA-HF trial. Associations between baseline NT-proBNP levels, changes post-baseline and …