Medicine and Health Sciences Commons^™

Associated Radiation Exposure From Medical Imaging And Excess Lifetime Risk Of Developing Cancer In Pediatric Patients With Pulmonary Hypertension, Malini Mahendra, Philip Chu, Elena K Amin, Hythem Nawaytou, James R Duncan, Jeffrey R Fineman, Rebecca Smith-Bindman

2020-Current year OA Pubs

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures …

Safety And Efficacy Of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From A Phase 2, Randomized Clinical Trial In Pediatric Participants With Complicated Intra-Abdominal Infection, Carl-Christian A. Jackson, Jason Newland, Nataliia Dementieva, Julia Lonchar, Feng-Hsiu Su, Jennifer A. Huntington, Mekki Bensaci, Myra W. Popejoy, Matthew G. Johnson, Carisa De Anda, Elizabeth G. Rhee, Christopher J. Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole …

Validation Of A Farsi Version Of The Eating Disorder Examination Questionnaire (F-Ede-Q) In Adolescents And University Students From Iran, Reza N Sahlan, Jessica F Saunders, Patrycja Klimek-Johnson, Alexandra D Convertino, Jason M Lavender, Ellen E Fitzsimmons-Craft, Jason M Nagata

2020-Current year OA Pubs

BACKGROUND: Although the Farsi version of the Eating Disorder Examination-Questionnaire (F-EDE-Q) is frequently utilized to assess disordered eating in Iran, its factor structure, reliability, and validity have not been investigated in Iranian samples, which is the aim of the current investigation.

METHOD: Using convenience sampling, this study recruited 1112 adolescents and 637 university students to complete disordered eating and mental health-focused questionnaires, including the F-EDE-Q.

RESULTS: Confirmatory factor analyses of the 22 attitudinal items in the F-EDE-Q indicated that a brief seven-item, three-factor model (i.e., Dietary Restraint, Shape/Weight Overvaluation, Body Dissatisfaction with Shape and Weight) was the only factor structure …

Exploratory Genome-Wide Analyses Of Cortical Inhibition, Facilitation, And Plasticity In Late-Life Depression, Rafae A Wathra, Xiaoyu Men, Samar S M Elsheikh, Victoria S Marshe, Tarek K Rajji, Jennifer I Lissemore, Benoit H Mulsant, Jordan F Karp, Charles F Reynolds 3rd, Eric J Lenze, Zafiris J Daskalakis, Daniel J Müller, Daniel M Blumberger

2020-Current year OA Pubs

Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used …

The Highly Conserved Stem-Loop Ii Motif Is Dispensable For Sars-Cov-2, Hongbing Jiang, Astha Joshi, Tianyu Gan, Andrew B Janowski, Chika Fujii, Traci L Bricker, Tamarand L Darling, Houda H Harastani, Kuljeet Seehra, Stephen Tahan, Ana Jung, Binita Febles, Joshua A Blatter, Scott A Handley, Bijal A Parikh, David Wang, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth

Benefits Of A 12-Week Non-Drug "Brain Fitness Program" For Patients With Attention-Deficit/Hyperactive Disorder, Post-Concussion Syndrome, Or Memory Loss, Majid Fotuhi, Noah D Khorrami, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Non-pharmacologic interventions can potentially improve cognitive function, sleep, and/or mood in patients with attention-deficit/hyperactive disorder (ADHD), post-concussion syndrome (PCS), or memory loss.

OBJECTIVE: We evaluated the benefits of a brain rehabilitation program in an outpatient neurology practice that consists of targeted cognitive training, lifestyle coaching, and electroencephalography (EEG)-based neurofeedback, twice weekly (90 minutes each), for 12 weeks.

METHODS: 223 child and adult patients were included: 71 patients with ADHD, 88 with PCS, and 64 with memory loss (mild cognitive impairment or subjective cognitive decline). Patients underwent a complete neurocognitive evaluation, including tests for Verbal Memory, Complex Attention, Processing Speed, …

A Moment Kernel Machine For Clinical Data Mining To Inform Medical Decision Making, Yao-Chi Yu, Wei Zhang, David O'Gara, Jr-Shin Li, Su-Hsin Chang

2020-Current year OA Pubs

Machine learning-aided medical decision making presents three major challenges: achieving model parsimony, ensuring credible predictions, and providing real-time recommendations with high computational efficiency. In this paper, we formulate medical decision making as a classification problem and develop a moment kernel machine (MKM) to tackle these challenges. The main idea of our approach is to treat the clinical data of each patient as a probability distribution and leverage moment representations of these distributions to build the MKM, which transforms the high-dimensional clinical data to low-dimensional representations while retaining essential information. We then apply this machine to various pre-surgical clinical datasets to …

Etv2 Primes Hematoendothelial Gene Enhancers Prior To Hematoendothelial Fate Commitment, Jeffrey D Steimle, Chul Kim, Megan Rowton, Rangarajan D Nadadur, Zhezhen Wang, Matthew Stocker, Andrew D Hoffmann, Erika Hanson, Junghun Kweon, Tanvi Sinha, Kyunghee Choi, Brian L Black, John M Cunningham, Ivan P Moskowitz, Kohta Ikegami

2020-Current year OA Pubs

Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of …

Neuraminidase Activity Modulates Cellular Coinfection During Influenza A Virus Multicycle Growth, Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey

2020-Current year OA Pubs

Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA's ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic …

Inclusive Recruitment Strategies To Maximize Sociodemographic Diversity Among Participants: A St. Louis Case Study, Chelsey R. Carter, Julia Maki, Nicole Ackermann, Erika A. Waters

2020-Current year OA Pubs

UNLABELLED:

HIGHLIGHTS: We provide concrete strategies for recruiting, enrolling, and retaining a sociodemographically diverse study sample.We offer cost estimates for all stages of study recruitment and found that in-person recruitment was the most effective, but also the most expensive, way to identify Black participants and participants with no college experience.It is critical for investigators to have access to institutional infrastructure and resources to support conducting research that is inclusive of diverse sociodemographic groups.An intentionally diverse recruitment staff supports a diverse study sample.

Histidine-Rich Protein Ii Nanoparticle Delivery Of Heme Iron Load Drives Endothelial Inflammation In Cerebral Malaria, Suong T Nguyen, Daniel Du, Daniel Wychrij, Matthew D Cain, Qingping Wu, Robyn S Klein, Ilaria Russo, Daniel E Goldberg

2020-Current year OA Pubs

Histidine-rich protein II (HRPII) is secreted by

A Comprehensive Assay Of Social Motivation Reveals Sex-Specific Roles Of Autism-Associated Genes And Oxytocin, Susan E Maloney, Simona Sarafinovska, Claire Weichselbaum, Katherine B Mccullough, Raylynn G Swift, Yating Liu, Joseph D Dougherty

2020-Current year OA Pubs

Social motivation is critical to the development of typical social functioning. Social motivation, specifically one or more of its components (e.g., social reward seeking or social orienting), could be relevant for understanding phenotypes related to autism. We developed a social operant conditioning task to quantify effort to access a social partner and concurrent social orienting in mice. We established that mice will work for access to a social partner, identified sex differences, and observed high test-retest reliability. We then benchmarked the method with two test-case manipulations.

On The Dependent Recognition Of Some Long Zinc Finger Proteins, Zheng Zuo, Timothy Billings, Michael Walker, Petko M Petkov, Polly M Fordyce, Gary D Stormo

2020-Current year OA Pubs

The human genome contains about 800 C2H2 zinc finger proteins (ZFPs), and most of them are composed of long arrays of zinc fingers. Standard ZFP recognition model asserts longer finger arrays should recognize longer DNA-binding sites. However, recent experimental efforts to identify in vivo ZFP binding sites contradict this assumption, with many exhibiting short motifs. Here we use ZFY, CTCF, ZIM3, and ZNF343 as examples to address three closely related questions: What are the reasons that impede current motif discovery methods? What are the functions of those seemingly unused fingers and how can we improve the motif discovery algorithms based …

Structural Specializations Of The Sperm Tail, Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang, Marc C Roelofs, Wei Huang, Riccardo Zenezini Chiozzi, Johannes F Hevler, Albert J R Heck, Susan K Dutcher, Alan Brown, Rui Zhang, Tzviya Zeev-Ben-Mordehai

2020-Current year OA Pubs

Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which is increasing globally. Sperm are powered by a microtubule-based molecular machine-the axoneme-but it is unclear how axonemal microtubules are ornamented to support motility in diverse fertilization environments. Here, we present high-resolution structures of native axonemal doublet microtubules (DMTs) from sea urchin and bovine sperm, representing external and internal fertilizers. We identify >60 proteins decorating sperm DMTs; at least 15 are sperm associated and 16 are linked to infertility. By comparing DMTs across species and cell types, we define core microtubule inner proteins …

Β Cell Function After Roux-En-Y Gastric Bypass Surgery Or Reduced Energy Intake Alone In People With Obesity, Bettina Mittendorfer, Bruce W. Patterson, Faidon Magkos, Mihoko Yoshino, David P. Bradley, J. Christopher Eagon, Samuel Klein

2020-Current year OA Pubs

BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, …

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Defining Diurnal Fluctuations In Mouse Choroid Plexus And Csf At High Molecular, Spatial, And Temporal Resolution, Ryann M Fame, Yong Zhang, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene …

A Simplified Method To Correct Saturation Of Arterial Input Function For Cardiac Magnetic Resonance First-Pass Perfusion Imaging: Validation With Simultaneously Acquired Pet, Ran Li, Masoud Edalati, David Muccigrosso, Jeffrey M C Lau, Richard Laforest, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: First-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on

METHODS: Sixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 …

A List-Mode Multi-Energy Window Low-Count Spect Reconstruction Method For Isotopes With Multiple Emission Peaks, Md Ashequr Rahman, Zekun Li, Zitong Yu, Richard Laforest, Daniel L J Thorek, Abhinav K Jha

2020-Current year OA Pubs

BACKGROUND: Single-photon emission computed tomography (SPECT) provides a mechanism to perform absorbed-dose quantification tasks for [Formula: see text]-particle radiopharmaceutical therapies ([Formula: see text]-RPTs). However, quantitative SPECT for [Formula: see text]-RPT is challenging due to the low number of detected counts, the complex emission spectrum, and other image-degrading artifacts. Towards addressing these challenges, we propose a low-count quantitative SPECT reconstruction method for isotopes with multiple emission peaks.

METHODS: Given the low-count setting, it is important that the reconstruction method extracts the maximal possible information from each detected photon. Processing data over multiple energy windows and in list-mode (LM) format provide mechanisms …

Striatal Dopamine Synthesis And Cognitive Flexibility Differ Between Hormonal Contraceptive Users And Nonusers, Caitlin M Taylor, Daniella J Furman, Anne S Berry, Robert L White, William J Jagust, Mark D'Esposito, Emily G Jacobs

2020-Current year OA Pubs

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Healthy Lifestyle Index And Risk Of Cardiovascular Disease Among Postmenopausal Women With Normal Body Mass Index, Rita Peila, Xiaonan Xue, Qibin Qi, Andrew J Dannenberg, Matthew A Allison, Karen C Johnson, Michael J Lamonte, Robert A Wild, Bernhard Haring, Kathy Pan, Hilary A Tindle, Randi Foraker, Nazmus Saquib, Ana Barac, Thomas E Rohan

2020-Current year OA Pubs

Background A lifestyle comprising a healthy diet, light alcohol consumption, no smoking, and moderate or intense physical activity has been associated with reduced risk of cardiovascular disease (CVD). We examined the association of a healthy lifestyle index (HLI), derived from scores for each of these components plus waist circumference, with the risk of incident CVD and CVD subtypes in postmenopausal women with normal body mass index (18.5-<25.0 kg/m

Robust Acoustic Trapping And Perturbation Of Single-Cell Microswimmers Illuminate Three-Dimensional Swimming And Ciliary Coordination, Mingyang Cui, Susan K Dutcher, Philip V Bayly, J Mark Meacham

2020-Current year OA Pubs

We report a label-free acoustic microfluidic method to confine single, cilia-driven swimming cells in space without limiting their rotational degrees of freedom. Our platform integrates a surface acoustic wave (SAW) actuator and bulk acoustic wave (BAW) trapping array to enable multiplexed analysis with high spatial resolution and trapping forces that are strong enough to hold individual microswimmers. The hybrid BAW/SAW acoustic tweezers employ high-efficiency mode conversion to achieve submicron image resolution while compensating for parasitic system losses to immersion oil in contact with the microfluidic chip. We use the platform to quantify cilia and cell body motion for wildtype biciliate …

A Review Of Social Media Platform Policies That Address Cannabis Promotion, Marketing And Sales, Carla J Berg, Cassidy R Loparco, Yuxian Cui, Alexandria Pannell, Grace Kong, Lynniah Griffith, Katelyn F Romm, Y Tony Yang, Yan Wang, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: Cannabis marketing exposure via social media may impact use in youth and young adults. Most states with recreational cannabis lack policies regarding social media-based marketing. Thus, we examined such policies among prominent platforms, particularly those popular among youth and young adults.

METHODS: In September-October 2022, 3 research team members extracted policies applying to the general community, advertising, and any specific content regarding drug-related content for 11 social media sites: Discord, Facebook, Instagram, Pinterest, Reddit, Snapchat, TikTok, Tumblr, Twitch, Twitter, and YouTube. Using inductive thematic analysis, they then dual-coded restrictions on cannabis-related content (e.g., paid advertising, unpaid promotion, sales). Descriptive …

Use Of Novel Structural Features To Identify Urinary Biomarkers During Acute Kidney Injury That Predict Progression To Chronic Kidney Disease, Jennifer R Charlton, Teng Li, Teresa Wu, Kimberly Deronde, Yanzhe Xu, Edwin J Baldelomar, Kevin M Bennett

2020-Current year OA Pubs

BACKGROUND: A significant barrier to biomarker development in the field of acute kidney injury (AKI) is the use of kidney function to identify candidates. Progress in imaging technology makes it possible to detect early structural changes prior to a decline in kidney function. Early identification of those who will advance to chronic kidney disease (CKD) would allow for the initiation of interventions to halt progression. The goal of this study was to use a structural phenotype defined by magnetic resonance imaging and histology to advance biomarker discovery during the transition from AKI to CKD.

METHODS: Urine was collected and analyzed …

Social Determinants Of Health And Us Cancer Screening Interventions: A Systematic Review, Ariella R Korn, Callie Walsh-Bailey, Margarita Correa-Mendez, Peter Delnero, Meagan Pilar, Brittney Sandler, Ross C Brownson, Karen M Emmons, April Y Oh

2020-Current year OA Pubs

There remains a need to synthesize linkages between social determinants of health (SDOH) and cancer screening to reduce persistent inequities contributing to the US cancer burden. The authors conducted a systematic review of US-based breast, cervical, colorectal, and lung cancer screening intervention studies to summarize how SDOH have been considered in interventions and relationships between SDOH and screening. Five databases were searched for peer-reviewed research articles published in English between 2010 and 2021. The Covidence software platform was used to screen articles and extract data using a standardized template. Data items included study and intervention characteristics, SDOH intervention components and …

Genetic Deletion Of Skeletal Muscle Ipla2Γ Results In Mitochondrial Dysfunction, Muscle Atrophy And Alterations In Whole-Body Energy Metabolism, Sung Ho Moon, Beverly Gibson Dilthey, Shaoping Guan, Harold F Sims, Sara K Pittman, Amy L Keith, Christopher M Jenkins, Conrad C Weihl, Richard W Gross

2020-Current year OA Pubs

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPLA

Treatment Decisions And The Use Of Mek Inhibitors For Children With Neurofibromatosis Type 1-Related Plexiform Neurofibromas, Amy E Armstrong, Allan J Belzberg, John R Crawford, Angela C Hirbe, Zhihong J Wang

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with …

A Refined, Controlled 16s Rrna Gene Sequencing Approach Reveals Limited Detection Of Cerebrospinal Fluid Microbiota In Children With Bacterial Meningitis, Christopher E. Pope, Kathryn B. Whitlock, Paul Hodor, David D. Limbrick Jr, Patrick J. Mcdonald, Jason Hauptman, Lucas R Hoffman, Tamara D. Simon

2020-Current year OA Pubs

Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads, such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples with low bacterial loads by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial …

Comprehensive Functional Characterization Of Sgcb Coding Variants Predicts Pathogenicity In Limb-Girdle Muscular Dystrophy Type R4/2e, Chengcheng Li, Jackson Wilborn, Sara Pittman, Jil Daw, Jorge Alonso-Pérez, Jordi Díaz-Manera, Conrad C. Weihl, Gabe Haller

2020-Current year OA Pubs

Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in β-sarcoglycan (SGCB). Together, β-, α-, γ-, and δ-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface …