Medicine and Health Sciences Commons^™

Burst Steroid Therapy And Quality Of Life In Patients With Acute Heart Failure: Insights From The Cortahf Trial, Matteo Pagnesi, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Patients hospitalized with acute heart failure (AHF) treated with a 7 day prednisone course in the CORTAHF pilot trial had a greater improvement in health-related quality of life (QoL) at Day 7 in both the overall population and in patients with baseline interleukin 6 > 13 pg/mL. This post-hoc analysis examines the specific QoL domains and the relationship between clinical signs of congestion and QoL.

METHODS: In the CORTAHF pilot trial, patients with AHF and high-sensitivity C-reactive protein (hsCRP) > 20 mg/L were randomized 1:1 to once-daily oral 40 mg prednisone for 7 days plus usual care or usual care alone. …

Changes In The Fxr-Cistrome And Alterations In Bile Acid Physiology In Wilson Disease, Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore

Children’s Nutrition Research Center Staff Publications

Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.

Methods: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.

Results: FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Innovations In Intestinal Organoid Technology Featuring An Open Apical Surface, Ye Chen, Yi Wang

2020-Current year OA Pubs

Since the development of the three-dimensional (3D) "mini-gut" culture system, adult stem cell-derived organoid technology has rapidly advanced, providing in vitro models that replicate key cellular, molecular, and physiological properties of multiple organs. The 3D intestinal organoid system has resolved many long-standing challenges associated with immortalized or cancer cell cultures, offering unparalleled capabilities for modeling gastrointestinal development and diseases. However, significant limitations remain, including restricted accessibility to the epithelial apical surface for studying host-microbe interactions, interruptions in modeling chronic gastrointestinal diseases due to frequent passaging and dissociation, and the absence of mechanical cues such as peristalsis and luminal flow, which …

Rna Interference In Protozoan Parasites And Its Application, Lon-Fye Lye, Deborah E Dobson, Stephen M Beverley, Min-Che Tung

2020-Current year OA Pubs

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression, via small RNA triggers derived from double-stranded RNA that can target specific genes; it is a natural process that plays a role in both the regulation of protein synthesis and in immunity. Discovery of RNAi by Fire and Mello in 1998 had a profound impact on unraveling novel aspects of eukaryotic biology. RNA interference (RNAi) has proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms. A great advance in …

Spatiotemporal Association Of Coronavirus Disease 2019 Cases And Deaths With Exposure To Wildfire Particulate Matter In 2020, Thomas C Mchale, David R Boulware, Kelly Searle, Leda Kobziar, Phinehas Lampman, Julio C Zuniga-Moya, Ben Papadopoulos, Andrej Spec, Naomi E Hauser, George R Thompson

2020-Current year OA Pubs

BACKGROUND: Climate change is anticipated to have profound effects on human health, including in infectious diseases. Wildfires have been increasing in frequency and intensity due to climate change and have been linked to worsening respiratory disease outcomes. We aimed to demonstrate whether there was an association between wildfire smoke and coronavirus disease 2019 (COVID-19) in California during 2020.

METHODS: We used an ecologic cohort study with a spatial autoregressive model to test for associations between wildfire smoke, measured as particulate matter < 2.5 µg/m

RESULTS: In an adjusted analysis, we found a 1-month lag increase of 203 COVID-19 cases per 10 000 persons …

Large-Scale Network Analysis Of The Cerebrospinal Fluid Proteome Identifies Molecular Signatures Of Frontotemporal Lobar Degeneration, Rowan Saloner, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic …

Screpertoire 2: Enhanced And Efficient Toolkit For Single-Cell Immune Profiling, Qile Yang, Ksenia R. Safina, Kieu Diem Quynh Nguyen, Zewen Kelvin Tuong, Nicholas Borcherding

2020-Current year OA Pubs

Single-cell adaptive immune receptor repertoire sequencing (scAIRR-seq) and single-cell RNA sequencing (scRNA-seq) provide a transformative approach to profiling immune responses at unprecedented resolution across diverse pathophysiologic contexts. This work presents scRepertoire 2, a substantial update to our R package for analyzing and visualizing single-cell immune receptor data. This new version introduces an array of features designed to enhance both the depth and breadth of immune receptor analysis, including improved workflows for clonotype tracking, repertoire diversity metrics, and novel visualization modules that facilitate longitudinal and comparative studies. Additionally, scRepertoire 2 offers seamless integration with contemporary single-cell analysis frameworks like Seurat and …

Cysteine Depletion Triggers Adipose Tissue Thermogenesis And Weight Loss, Aileen H Lee, Irina Shchukina, Prabhakar Sairam Andhey, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes lethal weight loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine-restriction-induced adipose browning and weight loss requires sympathetic nervous system-derived noradrenaline signalling via …

Telemedicine In Nerve Surgery: An Effective Method To Determine Indications For Surgery, Noah S. Llaneras, Ruby L. Taylor, Jonah P. M. Orr, Rachel Alessio, Carolyn Carper, Brendan M. Patterson, Susan E. Mackinnon

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic accelerated the adoption of telemedicine for surgical consultations. Although patient satisfaction has been well documented, limited research exists regarding telemedicine's effectiveness in determining the ability to indicate for surgical care compared with in-office visits. We conducted a retrospective review comparing surgical decision-making via telemedicine versus in-person consultations, hypothesizing that in-office visits would be more effective in establishing a surgical plan than telemedicine.

METHODS: A retrospective review of the medical records of all new patients presenting to the senior author's nerve surgery clinic at a high-volume quaternary referral center between June 2020 and January 2023 was performed. …

Correlation Of Ultrasound And Electrodiagnostic Evaluation In Ballistic Peripheral Nerve Injuries, Mitchell S. Mologne, Zachary D. Randall, Nathan P. Olafsen, David M. Brogan, Christopher J. Dy

2020-Current year OA Pubs

BACKGROUND: Evaluation and management of ballistic peripheral nerve injuries remain controversial, and recent series have suggested higher rates of nerve discontinuity than previously appreciated. Ultrasound (US) may aid clinicians in the management of ballistic injuries. The goal of this study was to compare US findings to electrodiagnostic and intraoperative findings to assess its accuracy in ballistic injuries.

METHODS: We conducted a retrospective review of patients with the following criteria: (1) ballistic injury to the upper or lower extremity with suspected mixed or motor peripheral nerve injury; (2) underwent electrodiagnostic studies (EDX) and peripheral nerve ultrasound. US findings were categorized as …

Aortic Rupture During Transcatheter Aortic Valve Replacement Requiring Emergent Thoracic Endovascular Aortic Repair And Endograft Infection Requiring Endograft Explant, Ryan Wahidi, Dan Kindell, Puja Kachroo, J Westley Ohman

2020-Current year OA Pubs

Infection of endografts after thoracic endovascular aortic repair (TEVAR) is a catastrophic complication with dramatically high morbidity and mortality. We present the case of a 58-year-old gentleman who underwent TEVAR for aortic rupture during transcatheter aortic valve replacement, later presenting with TEVAR infection, endocarditis, and aortobronchial fistula who underwent TEVAR explantation, aortic valve replacement, and aortic reconstruction. The patient consented to publication of his operative course.

Genetically Encoded Biosensors Of Metabolic Function For The Study Of Neurodegeneration, A Review And Perspective, Minglei Zhao, Saman Behboudi Tanourlouee, Sean Mccracken, Philip R Williams

2020-Current year OA Pubs

Nervous system tissue is the most metabolically active in the body and neurons are the primary consumers of oxygen and metabolites in nervous tissue. Many processes support neuronal metabolism, and dysregulation of these processes or intrinsic neuronal metabolism is often tied to neurodegenerative diseases. While many techniques are available to query metabolic function and disease (e.g. Seahorse XF, histology, immunostaining), almost all of these approaches are destructive and few offer cellular resolution. However, genetically encoded biosensors can optically measure metabolic features in any tissue with optical access. Biosensors represent an approach to non-destructively monitor metabolic components and regulatory signaling repeatedly …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Phase 2 Multi-Arm Study Of Magrolimab Combinations In Patients With Acute Myeloid Leukaemia, Gabriel N Mannis, Camille N Abboud, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML.

METHODS: Endpoints included complete remission rate (CRR), overall response rate (ORR), overall survival (OS) and safety.

RESULTS: Eighteen and 36 patients were enrolled into the unfit and R/R AML arms, respectively. CRR was 38.9% and 25.0%, ORR was 66.7% and 38.9%, and median OS was 15.3 and 10.5 months in the unfit AML and R/R AML arms, respectively. No dose-limiting toxicities or magrolimab-related deaths occurred.

CONCLUSION: Magrolimab was safely combined with existing AML therapies with no new safety …

Clinical Trial Readiness In Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Amanda Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials.

METHODS: Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the …

Chronic, Battery-Free, Fully Implantable Multimodal Spinal Cord Stimulator For Pain Modulation In Small Animal Models, Allie J Widman, Taron Bashar, Alex Burton, David Marshall Clausen, Prashant Gupta, Drew K Wolf, Jakayla Folarin-Hines, Maria Payne, John A Rogers, Kathleen W Meacham, Robert W Gereau, Philipp Gutruf

2020-Current year OA Pubs

Spinal cord stimulation (SCS) for chronic pain management is an invasive therapy involving surgical implantation of electrodes into spinal epidural space. While the clinical value and mechanistic action of the therapy is debated considerably in recent years, preclinical chronic studies employing rodent models can provide invaluable insights regarding the balance between efficacy and complications as well as mechanistic understanding of SCS therapy. However, current rodent compatible devices require tethered power delivery or bulky batteries, severely limiting the ability to probe long-term efficacy of SCS therapy. This work introduces a tether-free, small-footprint, fully implantable, battery-free SCS device compatible with rodent models, …

Claustrum Volume Is Reduced In Multiple Sclerosis And Predicts Disability, Nicole Shelley, Bradley Judge, Dmitriy A Yablonskiy, Robert T Naismith, Matthew R Brier, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS).

METHODS: This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation.

RESULTS: …

Masseter Muscle Size In Chronic Parotid Sialadenitis, Erika M Stephens, William E Nesmith, M Allison Ogden, Jolie L Chang

2020-Current year OA Pubs

OBJECTIVE: The relationship between masseter muscle thickness and parotid duct obstruction resulting in recurrent sialadenitis is not well defined. This study aims to evaluate masseter muscle size in patients with chronic sialadenitis of the parotid and compared to patients without parotid sialadenitis.

METHODS: Data was collected retrospectively from patients with symptomatic chronic sialadenitis of the parotid or submandibular glands. Measurements of the masseter and lateral pterygoid muscles were performed on CT or MRI imaging by two investigators who were blinded to the symptomatic gland location. Masseter thickness in the region of the parotid duct trajectory was measured.

RESULTS: Out of …

Corneal Characteristics In Children With Marfan Syndrome With Or Without Ectopia Lentis, Marisa O'Brien, Lawrence Tychsen

2020-Current year OA Pubs

IMPORTANCE: Myopia of Marfan syndrome (MFS) may be ascribed to crystalline lens subluxation, abnormal corneal curvature, and increased globe axial length. Few studies have reported these measures in MFS children who did or did not have ectopia lentis (EL).

OBJECTIVE: To measure eye findings longitudinally in MFS children with and without EL.

METHODS: A prospective, comparative case study was conducted on 24 MFS children (48 eyes). EL necessitated lensectomy and intraocular lens implantation surgery in 16/24 children (mean age 5.6 ± 2.8 years). The remaining 8/24 MFS children (mean age 11.2 ± 4.2 years) had no EL and were phakic. …

Mollusc And Crustacean Consumption In The First 1000 Days: A Scoping Review, Brietta M Oaks, Emmanuel A Gyimah, Eliza Kleban, Kathleen Ragsdale, Lora L Iannotti

2020-Current year OA Pubs

Mollusc and crustacean consumption in the first 1000 d may improve maternal and child health by providing essential nutrients. However, in some contexts, molluscs and crustaceans have been associated with allergies and environmental contamination, potentially leading to adverse health and development outcomes. It is unclear whether the health benefits of consuming molluscs and crustaceans, collectively classified as shellfish in nutrition, are outweighed by the potential risks to pregnant women and children. We conducted a scoping review (PROSPERO: CRD42022320454) in PubMed, Scopus and EBSCO Global Health of articles published between January 2000 and March 2022 that assessed shellfish consumption during pregnancy, …

Scoping Literature Review To Identify Candidate Domains For The Omeract Systemic Lupus Erythematosus Core Outcome Set, Wils Nielsen, Alfred Kim, Et Al.

2020-Current year OA Pubs

No abstract provided.

Protocol For A Multisite, Parallel-Group, Randomized Clinical Trial Comparing A Brief Tele-Cognitive Behavioral Therapy Intervention (Bright) With Attention Control For The Reduction Of Body Image-Related Distress Among Head And Neck Cancer Survivors, Evan M Graboyes, Jessica R Vanderlan, Patrik Pipkorn, Sidharth V Puram

2020-Current year OA Pubs

One in four head and neck cancer (HNC) survivors experience clinically significant body image distress (BID), a devastating psychosocial morbidity that adversely affects quality of life. To date, effective interventions for these patients are lacking. BRIGHT (Building a Renewed ImaGe after Head and neck cancer Treatment), a brief cognitive behavioral treatment (CBT), has shown potential efficacy as a novel treatment paradigm for HNC survivors with BID. The primary objective of this randomized clinical trial (RCT) is to test the hypothesis that BRIGHT improves BID among HNC survivors relative to an Attention Control (AC) intervention. In this multisite RCT, N = …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Hiroko Yano, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

METHODS: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

RESULTS: NF2 loss-of-function (LOF) …

Hepatitis C Treatment Initiation During Hospitalization For People Who Use Drugs: A Narrative Review Of The Literature, Jacob Denkins, Jane Babiarz, Youngyoon Ham, Hayoung Ryu, Brian Ricci, Carissa Williams, Ian Alexander, Kendall Tucker, L Madeline Mccrary, Ximena Levander

2020-Current year OA Pubs

People who use drugs (PWUD) are increasingly acquiring and transmitting hepatitis C virus (HCV) and being admitted to the hospital for often costly non-HCV-related conditions. Traditionally, treatment of HCV has been deferred to the outpatient setting. However, outpatient HCV follow-up can be an arduous process to navigate with resultant gaps in care, especially for PWUD with numerous complex psychosocial and medical comorbidities. Hospitalization presents a key opportunity to initiate treatment, and several institutions have piloted inpatient treatment models with intensive outreach. We conducted a narrative review of peer-reviewed literature (2014-2024) evaluating hospital-based HCV treatment models for PWUD; 6 studies from …

Assessing Neurocognitive Maturation In Early Adolescence Based On Baby And Adult Functional Brain Landscapes, Omid Kardan, Muriah D Wheelock, Jiaxin Cindy Tu, Et Al.

2020-Current year OA Pubs

Adolescence is a period of growth in cognitive performance and functioning. Recently, data-driven measures of brain-age gap, which can index cognitive decline in older populations, have been utilized in adolescent data with mixed findings. Instead of using a data-driven approach, here we assess the maturation status of the brain functional landscape in early adolescence by directly comparing an individual's resting-state functional connectivity (rsFC) to the canonical early-life and adulthood communities. Specifically, we hypothesized that the degree to which a youth's connectome is better captured by adult networks compared to infant/toddler networks is predictive of their cognitive development. To test this …

White Matter Microstructure In School-Age Children With Down Syndrome, Dea Garic, Robert C Mckinstry, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution …

Measuring And Interpreting Individual Differences In Fetal, Infant, And Toddler Neurodevelopment, Halie A Olson, M Catalina Camacho, Natasha Marrus, Et Al.

2020-Current year OA Pubs

As scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a "standard" way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying "development" influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research …

A Systematic Review And Meta-Analysis Of Social Cognition Among People Living With Hiv: Implications For Non-Social Cognition And Social Everyday Functioning, David E Vance, Rebecca Billings, Crystal Chapman Lambert, Pariya L Fazeli, Burel R Goodin, Mirjam-Colette Kempf, Leah H Rubin, Bulent Turan, Jenni Wise, Gerhard Hellemann, Junghee Lee

2020-Current year OA Pubs

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% …

Plasma Mtbr-Tau243 Biomarker Identifies Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Rama K Koppisetti, Nicolas R Barthélemy, Yingxin He, Chihiro Sato, Brian A Gordon, Hong Jiang, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma …