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Determining Epigenetic Memory In Kidney Proximal Tubule Cell Derived Induced Pluripotent Stem Cells Using A Quadruple Transgenic Reprogrammable Mouse, Gabriel Khelifi, Theresa Chow, Jennifer Whiteley, Victoire Fort, Benjamin D Humphreys, Samer M I Hussein, Ian M Rogers

2020-Current year OA Pubs

The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this "epigenetic memory" influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed …

Wakeful Rest Benefits Recall, But Not Recognition, Of Incidentally Encoded Memory Stimuli In Younger And Older Adults, Peter R Millar, David A Balota

2020-Current year OA Pubs

Older adults exhibit deficits in episodic memory tasks, which have often been attributed to encoding or retrieval deficits, with little attention to consolidation mechanisms. More recently, researchers have attempted to measure consolidation in the context of a behavioral experiment using the wakeful rest paradigm (i.e., a brief, quiet period of minimal stimulation, which facilitates memory performance, compared to a distractor task). Critically, older adults might not produce this effect, given established age differences in other episodic memory processes and mind-wandering. In three experiments, we directly compared younger and older adults in modified versions of the wakeful rest paradigm. Critically, we …

Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al.

2020-Current year OA Pubs

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for …

Muscle-Specific Ablation Of Glucose Transporter 1 (Glut1) Does Not Impair Basal Or Overload-Stimulated Skeletal Muscle Glucose Uptake, Shawna L Mcmillin, Parker L Evans, William M Taylor, Luke A Weyrauch, Tyler J Sermersheim, Steven S Welc, Monique R Heitmeier, Richard C Hresko, Paul W Hruz, Francoise Koumanov, Geoffrey D Holman, E Dale Abel, Carol A Witczak

2020-Current year OA Pubs

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [

Cortex-Wide Response Mode Of Vip-Expressing Inhibitory Neurons By Reward And Punishment, Zoltán Szadai, Hyun-Jae Pi, Quentin Chevy, Katalin Ócsai, Dinu F Albeanu, Balázs Chiovini, Gergely Szalay, Gergely Katona, Adam Kepecs, Balázs Rózsa

2020-Current year OA Pubs

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity …

Dose-Dependent Von Willebrand Factor Inhibition By Aptamer Bb-031 Correlates With Thrombolysis In A Microfluidic Model Of Arterial Occlusion, Susan M Shea, Kimberly A Thomas, Rassam M G Rassam, Emily P Mihalko, Christina Daniel, Bruce A Sullenger, Philip C Spinella, Shahid M Nimjee

2020-Current year OA Pubs

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational …

Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled

2020-Current year OA Pubs

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the …

Structural Basis Of Synthetic Agonist Activation Of The Nuclear Receptor Rev-Erb, Meghan H Murray, Aurore Cecile Valfort, Thomas Koelblen, Céline Ronin, Fabrice Ciesielski, Arindam Chatterjee, Giri Babu Veerakanellore, Bahaa Elgendy, John K Walker, Lamees Hegazy, Thomas P Burris

2020-Current year OA Pubs

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity …

Evaluation Of Cisplatin-Induced Pathology In The Larval Zebrafish Lateral Line, David S Lee, Angela Schrader, Emily Bell, Mark E Warchol, Lavinia Sheets

2020-Current year OA Pubs

Cisplatin is an effective anticancer agent, but also causes permanent hearing loss by damaging hair cells-the sensory receptors essential for hearing. There is an urgent clinical need to protect cochlear hair cells in patients undergoing cisplatin chemotherapy. The zebrafish lateral line organ contains hair cells and has been frequently used in studies to screen for otoprotective compounds. However, these studies have employed a wide range of cisplatin dosages and exposure times. We therefore performed a comprehensive evaluation of cisplatin ototoxicity in the zebrafish lateral line with the goal of producing a standardized, clinically relevant protocol for future studies. To define …

An Mtorc1 To Hri Signaling Axis Promotes Cytotoxicity Of Proteasome Inhibitors In Multiple Myeloma, Odai Darawshi, Barbara Muz, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While mTORC1 inhibitors reduce MM viability and synergize with other therapies in vitro, clinically, mTORC1 inhibitors are not effective for MM. Here we show that the inactivation of mTORC1 is an intrinsic response of MM to PI treatment. Genetically enforced hyperactivation of mTORC1 in MM was sufficient to compromise tumorigenicity in mice. In vitro, mTORC1-hyperactivated MM cells gained …

Slc7a8 Is A Key Amino Acids Supplier For The Metabolic Programs That Sustain Homeostasis And Activation Of Type 2 Innate Lymphoid Cells, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Patrick F Rodrigues, Raki Sudan, Susan Gilfillan, Marina Cella, Steven J Van Dyken, Marco Colonna

2020-Current year OA Pubs

Group 2 innate lymphoid cells (ILC2) are innate counterparts of T helper 2 (Th2) cells that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 and IL-13 secretion. ILC2s depend on availability of arginine and branched-chain amino acids for sustaining cellular fitness, proliferation, and cytokine secretion in both steady state and upon activation. However, the contribution of amino acid transporters to ILC2 functions is not known. Here, we found that ILC2s selectively express

The Quality Of Energy- And Macronutrient-Balanced Diets Regulates Host Susceptibility To Influenza In Mice, Taylor A Cootes, Nayan D Bhattacharyya, Susie S Y Huang, Lina Daniel, Kim S Bell-Anderson, Sebastian A Stifter, Tracy Chew, Samantha M Solon-Biet, Luis R Saraiva, Yi Cai, Xinchun Chen, Stephen J Simpson, Carl G Feng

2020-Current year OA Pubs

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice …

Inhibiting Ack1-Mediated Phosphorylation Of C-Terminal Src Kinase Counteracts Prostate Cancer Immune Checkpoint Blockade Resistance, Dhivya Sridaran, Surbhi Chouhan, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Shambhavi Bhagwat, Melissa Reimers, Eric H Kim, Manish K Thakur, Muhammad A Saeed, Russell K Pachynski, Markus A Seeliger, W Todd Miller, Felix Y Feng, Nupam P Mahajan

2020-Current year OA Pubs

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8

Structural Basis For Mechanotransduction In A Potassium-Dependent Mechanosensitive Ion Channel, Jonathan Mount, Grigory Maksaev, Brock T Summers, James A J Fitzpatrick, Peng Yuan

2020-Current year OA Pubs

Mechanosensitive channels of small conductance, found in many living organisms, open under elevated membrane tension and thus play crucial roles in biological response to mechanical stress. Amongst these channels, MscK is unique in that its activation also requires external potassium ions. To better understand this dual gating mechanism by force and ligand, we elucidate distinct structures of MscK along the gating cycle using cryo-electron microscopy. The heptameric channel comprises three layers: a cytoplasmic domain, a periplasmic gating ring, and a markedly curved transmembrane domain that flattens and expands upon channel opening, which is accompanied by dilation of the periplasmic ring. …

Enterotoxigenic Escherichia Coli Heat-Labile Toxin Drives Enteropathic Changes In Small Intestinal Epithelia, Alaullah Sheikh, Brunda Tumala, Tim J Vickers, John C Martin, Bruce A Rosa, Subrata Sabui, Supratim Basu, Rita D Simoes, Makedonka Mitreva, Chad Storer, Erik Tyksen, Richard D Head, Wandy Beatty, Hamid M Said, James M Fleckenstein

2020-Current year OA Pubs

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene …

Imprinted Antibody Responses Against Sars-Cov-2 Omicron Sublineages, Young-Jun Park, Zhuoming Liu, Javier Janer, Sean P J Whelan, Herbert W Virgin, Et Al.

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after …

Sex Differences In Brain Tumor Glutamine Metabolism Reveal Sex-Specific Vulnerabilities To Treatment, Jasmin Sponagel, Jill K Jones, Cheryl Frankfater, Shanshan Zhang, Olivia Tung, Kevin Cho, Kelsey L Tinkum, Hannah Gass, Elena Nunez, Gary J Patti, Jingqin Luo, Joshua B Rubin, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue.

METHODS: Using positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity.

FINDINGS: We found that male glioblastoma …

An Allosteric Modulator Activates Bk Channels By Perturbing Coupling Between Ca2+ Binding And Pore Opening, Guohui Zhang, Xianjin Xu, Zhiguang Jia, Yanyan Geng, Hongwu Liang, Jingyi Shi, Martina Marras, Carlota Abella, Karl L Magleby, Jonathan R Silva, Jianhan Chen, Xiaoqin Zou, Jianmin Cui

2020-Current year OA Pubs

BK type Ca

Tuft-Cell-Intrinsic And -Extrinsic Mediators Of Norovirus Tropism Regulate Viral Immunity, Madison S Strine, Mia Madel Alfajaro, Vincent R Graziano, Jaewon Song, Leon L Hsieh, Ryan Hill, Jun Guo, Kelli L Vandussen, Robert C Orchard, Megan T Baldridge, Sanghyun Lee, Craig B Wilen

2020-Current year OA Pubs

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoV

A Human Stat3 Gain-Of-Function Variant Confers T Cell Dysregulation Without Predominant Treg Dysfunction In Mice, Erica G Schmitt, Kelsey A Toth, Samuel I Risma, Ana Kolicheski, Nermina Saucier, Rafael J. Feliciano Berríos, Zev J. Greenberg, Jennifer W. Leiding, Jack J. Bleesing, Akaluck Thatayatikom, Laura G. Schuettpelz, John R. Edwards, Tiphanie P. Vogel, Megan A Cooper

2020-Current year OA Pubs

Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease. However, the mechanisms of disease pathogenesis in STAT3 GOF syndrome remain largely unknown, and treatment is challenging. We developed a knock-in mouse model harboring a de novo pathogenic human STAT3 variant (p.G421R) …

Ornithine Decarboxylase Supports Ilc3 Responses In Infectious And Autoimmune Colitis Through Positive Regulation Of Il-22 Transcription, Vincent Peng, Siyan Cao, Tihana Trsan, Jennifer K Bando, Julian Avila-Pacheco, John L Cleveland, Clary Clish, Ramnik J Xavier, Marco Colonna

2020-Current year OA Pubs

Group 3 innate lymphoid cells (ILC3s) are RORγT

Oxidative Stress-Induced Cellular Senescence In Aging Retina And Age-Related Macular Degeneration, Ryo Terao, Tazbir Ahmed, Ayana Suzumura, Hiroko Terasaki

2020-Current year OA Pubs

Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, …

Single-Cell Multiomics Identifies Clinically Relevant Mesenchymal Stem-Like Cells And Key Regulators For Mpnst Malignancy, Lai Man Natalie Wu, Joshua Rubin, Et Al.

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumor (MPNST), a highly aggressive Schwann cell (SC)-derived soft tissue sarcoma, arises from benign neurofibroma (NF); however, the identity, heterogeneity and origins of tumor populations remain elusive. Nestin

Bi-Allelic Camsap1 Variants Cause A Clinically Recognizable Neuronal Migration Disorder, Reham Khalaf-Nazzal, Jennifer L Griffith, Joseph R Walsh, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T Curiel, Et Al.

2020-Current year OA Pubs

Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and …

Phenome-Wide Analysis Of Taiwan Biobank Reveals Novel Glycemia-Related Loci And Genetic Risks For Diabetes, Chia-Jung Lee, Ting-Huei Chen, Aylwin Ming Wee Lim, Chien-Ching Chang, Jia-Jyun Sie, Pei-Lung Chen, Su-Wei Chang, Shang-Jung Wu, Chia-Lin Hsu, Ai-Ru Hsieh, Wei-Shiung Yang, Cathy S J Fann

2020-Current year OA Pubs

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA

A Preclinical And Phase Ib Study Of Palbociclib Plus Nab-Paclitaxel In Patients With Metastatic Adenocarcinoma Of The Pancreas, Manuel Hidalgo, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

PURPOSE: To assess the preclinical efficacy, clinical safety and efficacy, and MTD of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

EXPERIMENTAL DESIGN: Preclinical activity was tested in patient-derived xenograft (PDX) models of PDAC. In the open-label, phase I clinical study, the dose-escalation cohort received oral palbociclib initially at 75 mg/day (range, 50‒125 mg/day; modified 3+3 design; 3/1 schedule); intravenous nab-paclitaxel was administered weekly for 3 weeks/28-day cycle at 100‒125 mg/m

RESULTS: Palbociclib plus nab-paclitaxel was more effective than gemcitabine plus nab-paclitaxel in three of four PDX models tested; the combination was not inferior to paclitaxel plus …

Comparison Of Plasma And Csf Biomarkers In Predicting Cognitive Decline, Andrew J Aschenbrenner, Yan Li, Rachel L Henson, Katherine Volluz, Jason Hassenstab, Philip Verghese, Tim West, Matthew R Meyer, Kristopher M Kirmess, Anne M Fagan, Chengjie Xiong, David Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler

2020-Current year OA Pubs

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer's disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.

METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over …

Herpes Simplex Virus And Rates Of Cognitive Decline Or Whole Brain Atrophy In The Dominantly Inherited Alzheimer Network, Charlotte Warren-Gash, Brian A Gordon, Eric Mcdade, Randall J Bateman, John C Morris, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN).

METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models …

Upper Limb Nerve Transfer Surgery In Patients With Tetraplegia, Saad Javeed, Christopher F Dibble, Jacob K Greenberg, Justin K Zhang, Jawad M Khalifeh, Yikyung Park, Thomas J Wilson, Eric L Zager, Amir H Faraji, Mark A Mahan, Lynda J Yang, Rajiv Midha, Neringa Juknis, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Cervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.

OBJECTIVE: To evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.

INTERVENTIONS: Nerve …

Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow

2020-Current year OA Pubs

No abstract provided.