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Bosutinib For Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia: Primary Results Of The Phase 4 Byond Study, Andreas Hochhaus, Camille Abboud, Et Al

Open Access Publications

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of …

Potential Pharmacological Agents For Covid-19, Anita Kotwani, Sumanth Gandra

Open Access Publications

A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At …

Growth Velocity In Children With Environmental Enteric Dysfunction Is Associated With Specific Bacterial And Viral Taxa Of The Gastrointestinal Tract In Malawian Children, Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Open Access Publications

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of …

Antibiotic Prescription Practices In Primary Care In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Giorgia Sulis, Pierrick Adam, Vaidehi Nafade, Genevieve Gore, Benjamin Daniels, Amrita Daftary, Jishnu Das, Sumanth Gandra, Madhukar Pai

Open Access Publications

BACKGROUND: The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate.

METHODS AND FINDINGS: We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. …

Evaluating The Use Of Rcbv As A Tumor Grade And Treatment Response Classifier Across Nci Quantitative Imaging Network Sites: Part Ii Of The Dsc-Mri Digital Reference Object (Dro) Challenge, Laura C. Bell, Hongyu An, Cihat Eldeniz, Richard Wahl, Et Al

Open Access Publications

We have previously characterized the reproducibility of brain tumor relative cerebral blood volume (rCBV) using a dynamic susceptibility contrast magnetic resonance imaging digital reference object across 12 sites using a range of imaging protocols and software platforms. As expected, reproducibility was highest when imaging protocols and software were consistent, but decreased when they were variable. Our goal in this study was to determine the impact of rCBV reproducibility for tumor grade and treatment response classification. We found that varying imaging protocols and software platforms produced a range of optimal thresholds for both tumor grading and treatment response, but the performance …

Potent, Specific Mepicides For Treatment Of Zoonotic Staphylococci, Rachel L. Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T. Shah, Justin J. Miller, Andrew J. Jezewski, Marwa O. Mikati, Xu Wang, Robert C. Brothers, Kenneth M. Heidel, Damon M. Osbourn, Carey-Ann D. Burnham, Sophie Alvarez, Stephanie A. Fritz, Cynthia S. Dowd, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) …

Repository Corticotropin Injection For Active Rheumatoid Arthritis Despite Aggressive Treatment: A Randomized Controlled Withdrawal Trial., Roy Fleischmann, Daniel E Furst, Erin Connolly-Strong, Jingyu Liu, Julie Zhu, Richard Brasington

Open Access Publications

INTRODUCTION: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs).

METHODS: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports.

RESULTS: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; …

Perspectives Of Patients On Outpatient Parenteral Antimicrobial Therapy: Experiences And Adherence, Yasir Hamad, Sai Dodda, Allison Frank, Joe Beggs, Christopher Sleckman, Glen Kleinschmidt, Michael A. Lane, Yvonne Burnett

Open Access Publications

Background: Nonadherence to medication is a burden to the US health care system and is associated with poor clinical outcomes. Data on outpatient parenteral antimicrobial therapy (OPAT) treatment plan adherence are lacking. The purpose of this study is to determine the rate of nonadherence and factors associated with it.

Methods: We surveyed patients discharged from a tertiary hospital on OPAT between February and August 2019 about their baseline characteristics, OPAT regimen, adherence, and experience with OPAT.

Results: Sixty-five patients responded to the survey. The median age was 62 years, and 56% were male. The rate of reported nonadherence to intravenous …

Impact Of Left Ventricular Assist Device Implantation On Mitral Regurgitation: An Analysis From The Momentum 3 Trial, Manreet K Kanwar, Keshava Rajagopal, Akinobu Itoh, Scott C Silvestry, Nir Uriel, Joseph C Cleveland, Christopher T Salerno, Douglas Horstmanshof, Daniel J Goldstein, Yoshifumi Naka, Stephen Bailey, Igor D Gregoric, Joyce Chuang, Poornima Sood, Mandeep R Mehra

Open Access Publications

BACKGROUND: Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated.

METHODS: We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2 years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms.

RESULTS: Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant …

Strategies To Optimize Icu Liberation (A To F) Bundle Performance In Critically Ill Adults With Coronavirus Disease 2019, John W Devlin, Hollis R O'Neal Jr, Christopher Thomas, Mary Ann Barnes Daly, Joanna L Stollings, David R Janz, E Wesley Ely, John C Lin

Open Access Publications

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, …

Conformational Distributions Of Isolated Myosin Motor Domains Encode Their Mechanochemical Properties, Justin R. Porter, Artur Meller, Maxwell I. Zimmerman, Michael J. Greenberg, Gregory R. Bowman

Open Access Publications

Myosin motor domains perform an extraordinary diversity of biological functions despite sharing a common mechanochemical cycle. Motors are adapted to their function, in part, by tuning the thermodynamics and kinetics of steps in this cycle. However, it remains unclear how sequence encodes these differences, since biochemically distinct motors often have nearly indistinguishable crystal structures. We hypothesized that sequences produce distinct biochemical phenotypes by modulating the relative probabilities of an ensemble of conformations primed for different functional roles. To test this hypothesis, we modeled the distribution of conformations for 12 myosin motor domains by building Markov state models (MSMs) from an …

Plasmodium Falciparum Translational Machinery Condones Polyadenosine Repeats, Slavica Pavlovic Djuranovic, Jessey Erath, Ryan J. Andrews, Peter O. Bayguinov, Joyce J. Chung, Douglas L. Chalker, James A.J. Fitzpatrick, Walter N. Moss, Pawel Szczesny, Sergej Djuranovic

Open Access Publications

No abstract provided.

Consensus Guideline For The Diagnosis And Treatment Of Tetrahydrobiopterin (Bh4) Deficiencies, Thomas Opladen, Toni S Pearson, Et Al

Open Access Publications

BACKGROUND: Tetrahydrobiopterin (BH

CONCLUSION: Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH

Study Protocol: Improving Cognition In People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial Of Cognitive Rehabilitation And Aerobic Exercise (Cogex), Anthony Feinstein, Amber Salter, Et Al

Open Access Publications

BACKGROUND: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, …

Nadph And Glutathione Redox Link Tca Cycle Activity To Endoplasmic Reticulum Homeostasis, Erica R Gansemer, Kyle S Mccommis, Michael Martino, Abdul Qaadir King-Mcalpin, Matthew J Potthoff, Brian N Finck, Eric B Taylor, D Thomas Rutkowski

Open Access Publications

Many metabolic diseases disrupt endoplasmic reticulum (ER) homeostasis, but little is known about how metabolic activity is communicated to the ER. Here, we show in hepatocytes and other metabolically active cells that decreasing the availability of substrate for the tricarboxylic acid (TCA) cycle diminished NADPH production, elevated glutathione oxidation, led to altered oxidative maturation of ER client proteins, and attenuated ER stress. This attenuation was prevented when glutathione oxidation was disfavored. ER stress was also alleviated by inhibiting either TCA-dependent NADPH production or Glutathione Reductase. Conversely, stimulating TCA activity increased NADPH production, glutathione reduction, and ER stress. Validating these findings, …

Site-Specific Siderocalin Binding To Ferric And Ferric-Free Enterobactin As Revealed By Mass Spectrometry, Chunyang Guo, Lindsey K Steinberg, Ming Cheng, Jong Hee Song, Jeffrey P Henderson, Michael L Gross

Open Access Publications

Both host and pathogen competitively manipulate coordination environments during bacterial infections. Human cells release the innate immune protein siderocalin (Scn, also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated lipocalin/NGAL) that can inhibit bacterial growth by sequestering iron in a ferric complex with enterobactin (Ent), the ubiquitous

Pediatric Reporting Of Genomic Results Study (Progress): A Mixed-Methods, Longitudinal, Observational Cohort Study Protocol To Explore Disclosure Of Actionable Adult- And Pediatric-Onset Genomic Variants To Minors And Their Parents, Juliann M Savatt, Jessica Mozersky, Et Al

Open Access Publications

BACKGROUND: Exome and genome sequencing are routinely used in clinical care and research. These technologies allow for the detection of pathogenic/likely pathogenic variants in clinically actionable genes. However, fueled in part by a lack of empirical evidence, controversy surrounds the provision of genetic results for adult-onset conditions to minors and their parents. We have designed a mixed-methods, longitudinal cohort study to collect empirical evidence to advance this debate.

METHODS: Pediatric participants in the Geisinger MyCode® Community Health Initiative with available exome sequence data will have their variant files assessed for pathogenic/likely pathogenic variants in 60 genes designated as actionable by …

Targeting Mitochondrial Fusion And Fission Proteins For Cardioprotection, Sauri Hernandez-Resendiz, Fabrice Prunier, Henrique Girao, Gerald Dorn, Derek J Hausenloy, Eu-Cardioprotection Cost Action (Ca16225)

Open Access Publications

New treatments are needed to protect the myocardium against the detrimental effects of acute ischaemia/reperfusion (IR) injury following an acute myocardial infarction (AMI), in order to limit myocardial infarct (MI) size, preserve cardiac function and prevent the onset of heart failure (HF). Given the critical role of mitochondria in energy production for cardiac contractile function, prevention of mitochondrial dysfunction during acute myocardial IRI may provide novel cardioprotective strategies. In this regard, the mitochondrial fusion and fissions proteins, which regulate changes in mitochondrial morphology, are known to impact on mitochondrial quality control by modulating mitochondrial biogenesis, mitophagy and the mitochondrial unfolded …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

Transcriptional Analyses Of Adult And Pediatric Adamantinomatous Craniopharyngioma Reveals Similar Expression Signatures Regarding Potential Therapeutic Targets, Eric Prince, Chibueze Agwu, David D Limbrick, Et Al

Open Access Publications

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential …

Radiation Induces Iatrogenic Immunosuppression By Indirectly Affecting Hematopoiesis In Bone Marrow, Vaishali Kapoor, Andrea Collins, Kaylan Griffith, Subhajit Ghosh, Nathan Wong, Xiaowei Wang, Grant A. Challen, Joseph Krambs, Dan Link, Dennis E. Hallahan, Dinesh Thotala

Open Access Publications

The immune system plays a vital role in cancer therapy, especially with the advent of immunotherapy. Radiation therapy induces iatrogenic immunosuppression referred to as radiation-induced lymphopenia (RIL). RIL correlates with significant decreases in the overall survival of cancer patients. Although the etiology and severity of lymphopenia are known, the mechanism(s) of RIL are largely unknown. We found that irradiation not only had direct effects on circulating lymphocytes but also had indirect effects on the spleen, thymus, and bone marrow. We found that irradiated cells traffic to the bone marrow and bring about the reduction of hematopoietic stem cells (HSC) and …

Mentored Training And Its Association With Dissemination And Implementation Research Output: A Quasi-Experimental Evaluation, Rebekah R Jacob, Angeline Gacad, Margaret Padek, Graham A Colditz, Karen M Emmons, Jon F Kerner, David A Chambers, Ross C Brownson

Open Access Publications

BACKGROUND: There is a continued need to evaluate training programs in dissemination and implementation (D&I) research. Scientific products yielded from trainees are an important and objective measure to understand the capacity growth within the D&I field. This study evaluates our mentored training program in terms of scientific productivity among applicants.

METHODS: Post-doctoral and early-career cancer researchers were recruited and applied to the R25 Mentored Training for Dissemination and Implementation Research in Cancer (MT-DIRC) between 2014 and 2017. Using application details and publicly available bibliometric and funding data, we compared selected fellows with unsuccessful applicants (nonfellows). We extracted Scopus citations and …

Switching To Lurasidone Following 12 Months Of Treatment With Risperidone: Results Of A 6-Month, Open-Label Study, Greg W Mattingly, Peter M Haddad, Michael Tocco, Jane Xu, Debra Phillips, Andrei Pikalov, Antony Loebel

Open Access Publications

BACKGROUND: Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS).

METHODS: The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) …

The Effects Of Vagus Nerve Stimulation On The Course And Outcomes Of Patients With Bipolar Disorder In A Treatment-Resistant Depressive Episode: A 5-Year Prospective Registry, R Hamish Mcallister-Williams, Soraia Sousa, Arun Kumar, Teresa Greco, Mark T Bunker, Scott T Aaronson, Charles R Conway, A John Rush

Open Access Publications

BACKGROUND: To compare illness characteristics, treatment history, response and durability, and suicidality scores over a 5-year period in patients with treatment-resistant bipolar depression participating in a prospective, multicenter, open-label registry and receiving Vagus Nerve Stimulation Therapy (VNS Therapy) plus treatment-as-usual (VNS + TAU) or TAU alone.

METHODS: Response was defined as ≥ 50% decrease from baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score at 3, 6, 9, or 12 months post-baseline. Response was retained while MADRS score remained ≥ 40% lower than baseline. Time-to-events was estimated using Kaplan-Meier (KM) analysis and compared using log-rank test. Suicidality was assessed using the …

De Novo Identification Of Toxicants That Cause Irreparable Damage To Parasitic Nematode Intestinal Cells, Douglas P. Jasmer, Bruce A. Rosa, Rahul Tyagi, Christina A. Bulman, Brenda Beerntsen, Joseph F. Urban Jr, Judy Sakanari, Makedonka Mitreva

Open Access Publications

Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based on de novo computational target prioritization of the 3,564 conserved intestine genes in A. suum, exocytosis was identified as a high priority pathway, and predicted inhibitors of exocytosis were tested using the large roundworm (Ascaris suum larval …

Effects Of Dopaminergic Drugs On Cognitive Control Processes Vary By Genotype, Daniella J Furman, Robert L White Iii, Jenna Naskolnakorn, Jean Ye, Andrew Kayser, Mark D'Esposito

Open Access Publications

Dopamine (DA) has been implicated in modulating multiple cognitive control processes, including the robust maintenance of task sets and memoranda in the face of distractors (cognitive stability) and, conversely, the ability to switch task sets or update the contents of working memory when it is advantageous to do so (cognitive flexibility). In humans, the limited specificity of available pharmacological probes has posed a challenge for understanding the mechanisms by which DA, acting on multiple receptor families across the PFC and striatum, differentially influences these cognitive processes. Using a within-subject, placebo-controlled design, we contrasted the impact of two mechanistically distinct DA …

Perceptions Of Us Adolescents And Adults With Sickle Cell Disease On Their Quality Of Care, Julie Kanter, Robert Gibson, Raymona H. Lawrence, Matthew P. Smeltzer, Norma L. Pugh, Jeffrey Glassberg, Rita V. Masese, Allison A. King, Cecelia Calhoun, Jane S. Hankins, Marsha Treadwell

Open Access Publications

Importance: Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, and previous studies have shown that individuals with SCD are affected by multiple health disparities, including stigmatization, inequities in funding, and worse health outcomes, which may preclude their ability to access quality health care. This needs assessment was performed as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to assess barriers to care that may be faced by individuals with SCD.

Objective: To assess the SCD-related medical care experience of adolescents and adults with SCD.

Design, Setting, and Participants: This one-time …

Rodent Arena Tracker (Rat): A Machine Vision Rodent Tracking Camera And Closed Loop Control System, Jonathan Krynitsky, Alex A Legaria, Julia J Pai, Marcial Garmendia-Cedillos, Ghadi Salem, Tom Pohida, Alexxai V Kravitz

Open Access Publications

Video tracking is an essential tool in rodent research. Here, we demonstrate a machine vision rodent tracking camera based on a low-cost, open-source, machine vision camera, the OpenMV Cam M7. We call our device the rodent arena tracker (RAT), and it is a pocket-sized machine vision-based position tracker. The RAT does not require a tethered computer to operate and costs about $120 per device to build. These features make the RAT scalable to large installations and accessible to research institutions and educational settings where budgets may be limited. The RAT processes incoming video in real-time at 15 Hz and saves

Deep Learning With Diffusion Basis Spectrum Imaging For Classification Of Multiple Sclerosis Lesions, Zezhong Ye, Ajit George, Anthony T Wu, Xuan Niu, Joshua Lin, Gautam Adusumilli, Robert T Naismith, Anne H Cross, Peng Sun, Sheng-Kwei Song

Open Access Publications

OBJECTIVE: Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion-defining patterns. Here we test this hypothesis by combining a deep learning algorithm using deep neural network (DNN) with DBSI and other imaging methods.

METHODS: Thirty-eight MS patients were scanned with diffusion-weighted imaging, magnetization transfer imaging, and standard conventional MRI sequences (cMRI). A total of 499 regions of interest were identified on standard MRI and labeled …

Applying Two General Population Job Exposure Matrices To Predict Incident Carpal Tunnel Syndrome: A Cross-National Approach To Improve Estimation Of Workplace Physical Exposures, Marcus Yung, Bradley A Evanoff, Skye Buckner-Petty, Yves Roquelaure, Alexis Descatha, Ann Marie Dale

Open Access Publications

Objectives A job exposure matrix (JEM) is a tool to estimate workers' exposure to occupational physical risk factors. We evaluated the performance of two general population JEM (CONSTANCES and O*NET) to detect known exposure-disease relationships in an American prospective cohort study. We compared exposure estimates from three data sources and explored whether combining exposures from these two JEM, or combining exposure from each JEM with individual-level measures, improved prediction of carpal tunnel syndrome (CTS). Methods Using Cox proportional hazard models, we evaluated relationships between physical work exposure and incident CTS of 2393 workers using JEM-assigned and individual-level measure exposure information. …