Digital Commons Network^™

Tourette Syndrome Research Highlights From 2022, Andreas Hartmann, Per Andrén, Cyril Atkinson-Clément, Virginie Czernecki, Cécile Delorme, Nanette Marinette Monique Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Keisuke Ueda, Kevin J. Black

2020-Current year OA Pubs

This is the ninth yearly article in the Tourette Syndrome Research Highlights series, summarizing selected research reports from 2022 relevant to Tourette syndrome. The authors briefly summarize reports they consider most important or interesting.

The Oral Selective Estrogen Receptor Degrader Gdc-0810 (Arn-810) In Postmenopausal Women With Hormone Receptor-Positive Her2-Negative (Hr + /Her2 -) Advanced/Metastatic Breast Cancer, Aditya Bardia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

METHODS: A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

RESULTS: Patients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose …

Scaling-Up Child And Youth Mental Health Services: Assessing Coverage Of A County-Wide Prevention And Early Intervention Initiative During One Fiscal Year, Cole Hooley, Deborah Salvo, Derek S Brown, Lauren Brookman-Frazee, Anna S Lau, Ross C Brownson, Patrick J Fowler, Debbie Innes-Gomberg, Enola K Proctor

2020-Current year OA Pubs

PURPOSE: In the U.S., the percentage of youth in need of evidence-based mental health practices (EBPs) who receive them (i.e., coverage rate) is low. We know little about what influences coverage rates. In 2010, the Los Angeles County Department of Mental Health (LACDMH) launched a reimbursement-driven implementation of multiple EBPs in youth mental health care. This study examines two questions: (1) What was the coverage rate of EBPs delivered three years following initial implementation? (2) What factors are associated with the coverage rates?

METHODS: To assess coverage rates of publicly insured youth, we used LACDMH administrative claims data from July …

Allele-Specific Quantification Of Human Leukocyte Antigen Transcript Isoforms By Nanopore Sequencing, Andrew E O Hughes, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

INTRODUCTION: While tens of thousands of HLA alleles have been identified by DNA sequencing, the contribution of alternative splicing to HLA diversity is not well characterized. In this study, we sought to determine if long-read sequencing could be used to accurately quantify allele-specific HLA transcripts in primary human lymphocytes.

METHODS: cDNA libraries were prepared from peripheral blood lymphocytes from 12 donors and sequenced by nanopore long-read sequencing. HLA reads were aligned to donor-specific reference sequences based on the known type of each donor. Allele-specific exon utilization was calculated as the proportion of reads aligning to each allele containing known exons, …

Patterns Of Utilization And Clinical Adoption Of 0.35 Tesla Mr-Guided Radiation Therapy In The United States - Understanding The Transition To Adaptive, Ultra-Hypofractionated Treatments, Michael D Chuong, Lauren E Henke, Et Al.

2020-Current year OA Pubs

PURPOSE/OBJECTIVE: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.

MATERIALS/METHODS: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.

RESULTS: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details …

Circulatory Arrest For Traumatic Brachiocephalic Artery Pseudoaneurysm Repair, Conor F Hynes, Kunal D Kotkar

2020-Current year OA Pubs

Blunt traumatic injuries to the brachiocephalic artery require surgical management. The operative technique used depends on the location of the injury, the patient's hemodynamic stability, and the surgeon's experience. Perfusion strategy can facilitate vascular control of the aortic arch and branch vessels. This report presents an urgent repair of a proximal posterior blunt traumatic brachiocephalic artery injury under circulatory arrest, with an excellent outcome.

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Health Utilities And Quality-Adjusted Life Years For Patients With Amyotrophic Lateral Sclerosis Receiving Reldesemtiv Or Placebo In Fortitude-Als, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Michael Butzner, Adriano Chiò, Jinsy A Andrews, Angela Genge, Dyfrig A Hughes, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner

2020-Current year OA Pubs

AIMS: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving

MATERIALS AND METHODS: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated

RESULTS: The full analysis set consisted of 456 patients (

CONCLUSIONS: This post hoc analysis of FORTITUDE-ALS suggests that

CLINICALTRIALS.GOV IDENTIFIER: NCT03160898.

Functional Divergence Of The Sarcomeric Myosin, Myh7b, Supports Species-Specific Biological Roles, Lindsey A. Lee, Samantha K. Barrick, Artur Meller, Jonathan Walklate, Jeffrey M. Lotthammer, Jian Wei Tay, W. Tom Stump, Gregory Bowman, Michael A. Geeves, Michael J. Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

Myosin heavy chain 7b (MYH7b) is an evolutionarily ancient member of the sarcomeric myosin family, which typically supports striated muscle function. However, in mammals, alternative splicing prevents MYH7b protein production in cardiac and most skeletal muscles and limits expression to a subset of specialized muscles and certain nonmuscle environments. In contrast, MYH7b protein is abundant in python cardiac and skeletal muscles. Although the MYH7b expression pattern diverges in mammals versus reptiles, MYH7b shares high sequence identity across species. So, it remains unclear how mammalian MYH7b function may differ from that of other sarcomeric myosins and whether human and python MYH7b …

Adapting An Intervention To Support Young Caregivers Of Cancer Survivors: A Study Protocol, Janet Njelesani, Melinda S. Kavanaugh, Jean Hunleth

2020-Current year OA Pubs

INTRODUCTION: Of the family members providing care, in the United States over 5.4 million are young people (<18 years of age) and they are the caregivers receiving the least support overall. Given the need to support cancer survivors through a family-centered practice approach, this lack of support and intervention for young caregivers represents a substantial gap in cancer care. In this study, we will adapt a young caregivers intervention, YCare, with young caregivers in families affected by cancer in order to advance support for families in cancer settings. YCare is an intervention that improves the support young caregivers provide through a peer-engaged, multidisciplinary model but has previously not been studied in the cancer care setting.

METHODS: Guided by the updated Consolidated Framework for Implementation Research (CFIR) we will engage stakeholders (i.e., young caregivers, cancer survivors, health care providers) using qualitative (i.e., one-on-one semi-structured interviews) and arts-based methods. Stakeholders will be recruited via cancer registries and community partners. Data will be analyzed descriptively using deductive (e.g., CFIR domains) and inductive (e.g., cancer practice settings) approaches.

DISCUSSION: The results will indicate the critical components for adapting the YCare intervention to the cancer practice context including new intervention elements and …

Cytosolic Epcam Cooperates With H-Ras To Regulate Epithelial To Mesenchymal Transition Through Zeb1, Fatma A. Omar, Taylor C. Brown, William E. Gillanders, Timothy P. Fleming, Michael A. Smith, Ross M. Bremner, Narendra V. Sankpal

2020-Current year OA Pubs

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, …

Diastolic Dysfunction Criteria And Heart Failure Readmission In Patients With Heart Failure And Reduced Ejection Fraction, Steven J. Lavine, Danielle Kelvas

2020-Current year OA Pubs

No abstract provided.

The Association Of Radiation Dose With Overall Survival For Patients Treated With Prostate Stereotactic Body Radiation Therapy, Michael R. Waters, Neal Andruska, Benjamin W. Fischer-Valuck, Temitope Agabalogun, Randall J. Brenneman, Hiram Gay, Jeff M. Michalski, Brian Baumann

2020-Current year OA Pubs

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/β = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials …

Innovations In Hematopoietic Stem-Cell Mobilization: A Review Of The Novel Cxcr4 Inhibitor Motixafortide, Zachary D. Crees, Michael P. Rettig, John F. Dipersio

2020-Current year OA Pubs

Hematopoietic stem-cell transplantation (HCT) and stem-cell-based gene therapies rely on the ability to collect sufficient CD34+ hematopoietic stem and progenitor cells (HSPCs), typically

Anti-Fibrotic Therapy And Lung Transplant Outcomes In Patients With Idiopathic Pulmonary Fibrosis, Todd L. Astor, Hilary J. Goldberg, Laurie D. Snyder, Andrew Courtwright, Ramsey Hachem, Tahuanty Pena, Lorenzo Zaffiri, Gerard J. Criner, Marie M. Budev, Tany Thaniyavarn, Thomas B. Leonard, Shaun Bender, Aliaa Barakat, Janis L. Breeze, Peter Lacamera

2020-Current year OA Pubs

BACKGROUND: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis.

OBJECTIVES: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications.

METHODS: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 …

Examining Decisional Needs And Contextual Factors Influencing Fertility Status Assessment Among Young Female Survivors Of Childhood Cancer: A Sequential Mixed Methods Study Protocol, Brooke Cherven, Nataliya V. Ivankova, Jessica B. Spencer, Anne M. Fitzpatrick, Karen C. Burns, Jenna Demedis, Holly R Hoefgen, Ann C. Mertens, James L. Klosky

2020-Current year OA Pubs

INTRODUCTION: Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health …

Study Protocol: A Cross-Sectional Survey Of Clinicians To Identify Barriers To Clinical Practice Guideline Implementation In The Assessment And Treatment Of Persistent Tic Disorders, Jaclyn M. Martindale, Harini Sarva, Davide Martino, Donald L. Gilbert, Christos Ganos, Tamara Pringsheim, Kevin J. Black, Irene A. Malaty

2020-Current year OA Pubs

INTRODUCTION: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines.

OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

X-Ray And Mr Contrast Bearing Nanoparticles Enhance The Therapeutic Response Of Image-Guided Radiation Therapy For Oral Cancer, Gayatri Sharma, Mir Hadi Razeghi Kondelaji, Guru P. Sharma, Christopher Hansen, Abdul K. Parchur, Shayan Shafiee, Jaidip M. Jagtap, Brian Fish, Carmen Bergom, Eric Paulson, William A. Hall, Heather A. Himburg, Amit Joshi

2020-Current year OA Pubs

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models.

METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated.

RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a …

Characterization Of Cerebrospinal Fluid (Csf) Microbiota At The Time Of Initial Surgical Intervention For Children With Hydrocephalus, Shailly Pandey, Kathryn B. Whitlock, Matthew R. Test, Paul Hodor, Christopher E. Pope, David D. Limbrick, Patrick J. Mcdonald, Jason S. Hauptman, Lucas R. Hoffman, Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in …

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …

Eating Disorders In Weight-Related Therapy (Edit): Protocol For A Systematic Review With Individual Participant Data Meta-Analysis Of Eating Disorder Risk In Behavioural Weight Management, Hiba Jebeile, Denise E. Wilfley, Et Al.

2020-Current year OA Pubs

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of …

Recruitment Methods And Yield Rates For A Multisite Clinical Trial Exploring Risk Reduction For Alzheimer's Disease (Rrad), Amanda N Szabo-Reed, Monica Sewell, Ellen F Binder, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease.

METHODS: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion.

RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) …

Human Deprivation Amblyopia: Treatment Insights From Animal Models, Kevin R Duffy, Mark F Bear, Nimesh B Patel, Vallabh E Das, Lawrence Tychsen

2020-Current year OA Pubs

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia …

Interobserver Variability In Target Definition For Stereotactic Arrhythmia Radioablation, Martijn H Van Der Ree, Phillip S Cuculich, Geoffrey D Hugo, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR.

METHODS: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated …

An Image-Based Modeling Framework For Predicting Spatiotemporal Brain Cancer Biology Within Individual Patients, Kamila M Bond, Lee Curtin, Sara Ranjbar, Ariana E Afshari, Leland S Hu, Joshua B Rubin, Kristin R Swanson

2020-Current year OA Pubs

Imaging is central to the clinical surveillance of brain tumors yet it provides limited insight into a tumor's underlying biology. Machine learning and other mathematical modeling approaches can leverage paired magnetic resonance images and image-localized tissue samples to predict almost any characteristic of a tumor. Image-based modeling takes advantage of the spatial resolution of routine clinical scans and can be applied to measure biological differences within a tumor, changes over time, as well as the variance between patients. This approach is non-invasive and circumvents the intrinsic challenges of inter- and intratumoral heterogeneity that have historically hindered the complete assessment of …

Training, Supervision, And Experience Of Coaches Offering Digital Guided Self-Help For Mental Health Concerns, Ellen E Fitzsimmons-Craft, Elsa Rojas, Naira Topooco, Gavin N Rackoff, Nur Hani Zainal, Daniel Eisenberg, Jillian Shah, Christina Desage, Denise E Wilfley, Craig Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital …

Evaluation Of Gliovascular Functions Of Aqp4 Readthrough Isoforms, Shayna M Mueller, Kelli Mcfarland White, Stuart B Fass, Siyu Chen, Zhan Shi, Xia Ge, John A Engelbach, Seana H Gaines, Annie R Bice, Michael J Vasek, Joel R Garbow, Joseph P Culver, Zila Martinez-Lozada, Martine Cohen-Salmon, Joseph D Dougherty, Darshan Sapkota

2020-Current year OA Pubs

Aquaporin-4 (AQP4) is a water channel protein that links the astrocytic endfeet to the blood-brain barrier (BBB) and regulates water and potassium homeostasis in the brain, as well as the glymphatic clearance of waste products that would otherwise potentiate neurological diseases. Recently, translational readthrough was shown to generate a C-terminally extended variant of AQP4, known as AQP4x, which preferentially localizes around the BBB through interaction with the scaffolding protein α-syntrophin, and loss of AQP4x disrupts waste clearance from the brain. To investigate the function of AQP4x, we generated a novel AQP4 mouse line (AllX) to increase relative levels of the …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Machine Learning Pipelines Developed For The Prediction Of Cancelation Of Inappropriate Parathyroid Hormone-Related Peptide Orders Demonstrate Poor Performance In Predicting Provider Behavior, Nicholas C. Spies, Christopher W. Farnsworth, Ronald Jackups, Mark A. Zaydman

2020-Current year OA Pubs

No abstract provided.