Medicine and Health Sciences Commons^™

Risk Of Autism Spectrum Disorder And Association Of Its Symptoms With Psychiatric And Substance Use Disorders In Non-Clinical Student Sample In Kenya: Cross-Sectional Study, Victoria N Mutiso, David M Ndetei, Esther N Muia, Monicah Masake, Rita K Alietsi, Lydia Onsinyo, Christine Musyimi, Daniel Mamah

2020-Current year OA Pubs

BACKGROUND: The prevalence and patterns of autism spectrum disorder (ASD) symptoms/traits and the associations of ASD with psychiatric and substance use disorders has not been documented in non-clinical students in Sub-Saharan Africa, and Kenya in particular.

AIMS: To document the risk level of ASD and its traits in a Kenyan student population (high school, college and university) using the Autism-Spectrum Quotient (AQ); and to determine the associations between ASD and other psychiatric and substance use disorders.

METHOD: This was a cross-sectional study among students (

RESULTS: Of the total sample, 54 (0.56%) were at high risk of ASD. Sociodemographic differences …

Transcranial Focused Ultrasound-Induced Blood‒Brain Barrier Opening In Mice Without Shaving Hairs, Lu Xu, Yan Gong, Chih-Yen Chien, Eric Leuthardt, Hong Chen

2020-Current year OA Pubs

Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil's high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood-brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs ("oil + hairs"), ultrasound gel with hair shaving ("ultrasound gel + no hair"), and ultrasound gel with hairs ("ultrasound gel + hairs"). The quality of the coupling was evaluated by [Formula: see text]-weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The …

Chromophore Carbonyl Twisting In Fluorescent Biosensors Encodes Direct Readout Of Protein Conformations With Multicolor Switching, Malin J Allert, Shivesh Kumar, You Wang, Lorena S Beese, Homme W Hellinga

2020-Current year OA Pubs

Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent response mechanisms which can be challenging to establish. We installed thiol-reactive derivatives of the naphthalene-based fluorophore Prodan into bacterial periplasmic glucose-binding proteins. Glucose binding elicited paired color exchanges in the excited and ground states of these conjugates. X-ray structures and mutagenesis studies established that glucose-mediated color switching arises from steric interactions that couple protein conformational changes to twisting of the Prodan carbonyl relative to its naphthalene plane. Mutations of residues contacting the carbonyl …

Differential Processing Of Risk And Reward In Delinquent And Non-Delinquent Youth, Natasha Duell, Michael T Perino, Ethan M Mccormick, Eva H Telzer

2020-Current year OA Pubs

The present study examined the behavioral and neural differences in risky decision-making between delinquent (n = 23) and non-delinquent (n = 27) youth ages 13-17 years (M = 16, SD = 0.97) in relation to reward processing. While undergoing functional neuroimaging, participants completed an experimental risk task wherein they received feedback about the riskiness of their behavior in the form of facial expressions that morphed from happy to angry. Behavioral results indicated that delinquent youth took fewer risks and earned fewer rewards on the task than non-delinquent youth. Results from whole-brain analyses indicated no group differences in sensitivity to punishments …

Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al.

2020-Current year OA Pubs

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting …

Phase Iii Pivotal Comparative Clinical Trial Of Intranasal (Incovacc) And Intramuscular Covid 19 Vaccine (Covaxin®), Chandramani Singh, Michael S Diamond, David T Curiel, Et Al.

2020-Current year OA Pubs

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial, Chris A Rees, Fahd Ahmad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni

2020-Current year OA Pubs

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in

A Survey Of Surgical Patients' Perspectives And Preferences Towards General Anesthesia Techniques And Shared-Decision Making, Bethany R Tellor Pennington, Mary C Politi, Arbi Ben Abdallah, Allison M Janda, Ingrid Eshun-Wilsonova, Nastassjia G Debourbon, Lilly Siderowf, Heidi Klosterman, Sachin Kheterpal, Michael S Avidan

2020-Current year OA Pubs

BACKGROUND: The decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients' preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician.

METHODS: We conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both …

Strategies For Overcoming The Single-Molecule Concentration Barrier, David S White, Mackinsey A Smith, Baron Chanda, Randall H Goldsmith

2020-Current year OA Pubs

Fluorescence-based single-molecule approaches have helped revolutionize our understanding of chemical and biological mechanisms. Unfortunately, these methods are only suitable at low concentrations of fluorescent molecules so that single fluorescent species of interest can be successfully resolved beyond background signal. The application of these techniques has therefore been limited to high-affinity interactions despite most biological and chemical processes occurring at much higher reactant concentrations. Fortunately, recent methodological advances have demonstrated that this concentration barrier can indeed be broken, with techniques reaching concentrations as high as 1 mM. The goal of this Review is to discuss the challenges in performing single-molecule fluorescence …

Brain-Derived Neurotrophic Factor Dysregulation As An Essential Pathological Feature In Huntington's Disease: Mechanisms And Potential Therapeutics, Andrew Speidell, Noman Bin Abid, Hiroko Yano

2020-Current year OA Pubs

Brain-derived neurotrophic factor (BDNF) is a major neurotrophin whose loss or interruption is well established to have numerous intersections with the pathogenesis of progressive neurological disorders. There is perhaps no greater example of disease pathogenesis resulting from the dysregulation of BDNF signaling than Huntington's disease (HD)-an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive impairments associated with basal ganglia dysfunction and the ultimate death of striatal projection neurons. Investigation of the collection of mechanisms leading to BDNF loss in HD highlights this neurotrophin's importance to neuronal viability and calls attention to opportunities for therapeutic interventions. Using electronic database searches …

Mechanical Stiffness And Anisotropy Measured By Mre During Brain Development In The Minipig, Shuaihu Wang, Charlotte A Guertler, Ruth J Okamoto, Curtis L Johnson, Matthew D J Mcgarry, Philip V Bayly

2020-Current year OA Pubs

The relationship between brain development and mechanical properties of brain tissue is important, but remains incompletely understood, in part due to the challenges in measuring these properties longitudinally over time. In addition, white matter, which is composed of aligned, myelinated, axonal fibers, may be mechanically anisotropic. Here we use data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) to estimate anisotropic mechanical properties in six female Yucatan minipigs at ages from 3 to 6 months. Fiber direction was estimated from the principal axis of the diffusion tensor in each voxel. Harmonic shear waves in the brain were excited …

Brain Hubs Defined In The Group Do Not Overlap With Regions Of High Inter-Individual Variability, Derek M Smith, Brian T Kraus, Ally Dworetsky, Evan M Gordon, Caterina Gratton

2020-Current year OA Pubs

Connector 'hubs' are brain regions with links to multiple networks. These regions are hypothesized to play a critical role in brain function. While hubs are often identified based on group-average functional magnetic resonance imaging (fMRI) data, there is considerable inter-subject variation in the functional connectivity profiles of the brain, especially in association regions where hubs tend to be located. Here we investigated how group hubs are related to locations of inter-individual variability. To answer this question, we examined inter-individual variation at group-level hubs in both the Midnight Scan Club and Human Connectome Project datasets. The top group hubs defined based …

Risk-Adapted Treatment Strategies With Pre-Irradiation Chemotherapy In Pediatric Medulloblastoma: Outcomes From The Polish Pediatric Neuro-Oncology Group, Marta Perek-Polnik, Anne Cochrane, Jinli Wang, Marzanna Chojnacka, Monika Drogosiewicz, Iwona Filipek, Ewa Swieszkowska, Magdalena Tarasinska, Wiesława Grajkowska, Joanna Trubicka, Paweł Kowalczyk, Bożenna Dembowska-Bagińskai, Mohamed S Abdelbaki

2020-Current year OA Pubs

Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone for childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyzed treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy. A total of 153 patients from the Polish Pediatric Neuro-Oncology Group were included in the analysis. The median age at diagnosis was 8.0 years, and median follow-up time was 6.4 years. Sixty-seven patients were classified as standard-risk and eighty-six as high-risk. …

Kinase Inhibitor Pulldown Assay Identifies A Chemotherapy Response Signature In Triple-Negative Breast Cancer Based On Purine-Binding Proteins, Junkai Wang, Alexander B Saltzman, Eric J Jaehnig, Jonathan T Lei, Anna Malovannaya, Matthew V Holt, Meggie N Young, Mothaffar F Rimawi, Foluso O Ademuyiwa, Meenakshi Anurag, Beom-Jun Kim, Matthew J Ellis

2020-Current year OA Pubs

UNLABELLED: Triple-negative breast cancer (TNBC) constitutes 10%-15% of all breast tumors. The current standard of care is multiagent chemotherapy, which is effective in only a subset of patients. The original objective of this study was to deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify kinases elevated in non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC before docetaxel- and carboplatin-based neoadjuvant chemotherapy. KIPA was applied to the native tumor lysates that were extracted from samples with high tumor content. Seven percent of …

Discovery And Targeting Of A Noncanonical Mechanism Of Sarcoma Resistance To Adi-Peg20 Mediated By The Microenvironment, Leonard C Rogers, Jeff C Kremer, Caitlyn B Brashears, Zongtao Lin, Alliny C S Bastos, Adriana Baker, Nicole Fettig, Dong Zhou, Kooresh I Shoghi, Carina A Dehner, John S A Chrisinger, Benjamin A Garcia, Toshinao Oyama, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

PURPOSE: Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 reexpression. This study examines the role of ASS1 silencing on tumor growth and initiation and identifies a noncanonical mechanism of resistance, aiming to improve clinical responses to ADI-PEG20.

EXPERIMENTAL DESIGN: Tumor initiation and growth rates were measured for a spontaneous Ass1 knockout (KO) murine sarcoma model. Tumor cell lines were generated, and resistance to arginine deprivation therapy was studied in vitro and …

Impact Of A Double Catastrophe, War And Covid-19, On Health Service Utilization Of A Tertiary Care Hospital In Tigray: An Interrupted Time-Series Study, Hiluf Ebuy Abraha, L Lewis Wall, Et Al.

2020-Current year OA Pubs

BACKGROUND: In developing nations with fragile healthcare systems, the effect of war is likely to be much worse than it would be in more developed countries. The presence of COVID-19 will also likely exacerbate the war's impact. This study set out to determine the effect of armed conflict and the COVID-19 pandemic on health service utilization at Ayder Comprehensive Specialized Hospital, in the Tigray region of Ethiopia.

METHODS: An interrupted time-series study design was used to analyze patient visits over forty-eight consecutive months (from July 2017 to June 2021) at inpatient, outpatient, and emergency departments. Data were analyzed using segmented …

Using Audit And Feedback To Guide Tailored Implementations Of Measurement-Based Care In Community Mental Health: A Multiple Case Study, Mira D H Snider, Meredith R Boyd, Madison R Walker, Byron J Powell, Cara C Lewis

2020-Current year OA Pubs

BACKGROUND: Audit and feedback (A&F) is an implementation strategy that can facilitate implementation tailoring by identifying gaps between desired and actual clinical care. While there are several theory-based propositions on which A&F components lead to better implementation outcomes, many have not been empirically investigated, and there is limited guidance for stakeholders when applying A&F in practice. The current study aims to illustrate A&F procedures in six community mental health clinics, with an emphasis on reporting A&F components that are relevant to theories of how feedback elicits behavior change.

METHODS: Six clinics from a larger trial using a tailored approach to …

Analysis Of Superficial Subcutaneous Fat Camper's And Scarpa's Fascia In A United States Cohort, David Z Chen, Aravinda Ganapathy, Yash Nayak, Christopher Mejias, Grace L Bishop, Vincent M Mellnick, David H Ballard

2020-Current year OA Pubs

Together, the Camper's and Scarpa's fasciae form the superficial fat layer of the abdominal wall. Though they have clinical and surgical relevance, little is known about their role in body composition across diverse patient populations. This study aimed to determine the relationship between patient characteristics, including sex and body mass index, and the distribution of Camper's and Scarpa's fascial layers in the abdominal wall. A total of 458 patients' abdominal CT examinations were segmented via CoreSlicer 1.0 to determine the surface area of each patient's Camper's, Scarpa's, and visceral fascia layers. The reproducibility of segmentation was corroborated by an inter-rater …

Pediatric Experience And Outcomes From The First Single-Vault Compact Proton Therapy Center, Stephanie M Perkins, Sabrina Prime, Michael Watts, Jiayi Huang, Tianyu Zhao

2020-Current year OA Pubs

The first single-vault compact proton therapy center opened in 2013, utilizing a gantry-mounted synchrocylotron. The center was placed within a large academic radiation oncology department with a high priority for pediatric cancer care. Here we performed a retrospective study of pediatric (≤21 years) patients treated with proton therapy at our institution between 2013-2022. Patient, tumor, and treatment characteristics were obtained including race, socioeconomic status, insurance type, distance travelled, need for anesthesia, and outside referrals for proton therapy. In total, 250 pediatric patients were treated with proton therapy comprising 18% of our proton patient volume. Median follow-up was 3.1 years, 38.4% …

The Effects Of Advanced Factor Analysis Approaches On Outcomes In Randomised Trials For Depression: Protocol For Secondary Analysis Of Individual Participant Data, Frank Doyle, David Byrne, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen Mcbride, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.

AIMS: We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.

METHOD: We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) …

Asset: Auto-Segmentation Of The Seventeen Segments For Ventricular Tachycardia Ablation In Radiation Therapy, Eric Morris, Robert Chin, Trudy Wu, Clayton Smith, Siamak Nejad-Davarani, Minsong Cao

2020-Current year OA Pubs

There has been a recent effort to treat high-risk ventricular tachycardia (VT) patients through radio-ablation. However, manual segmentation of the VT target is complex and time-consuming. This work introduces ASSET, or Auto-segmentation of the Seventeen SEgments for Tachycardia ablation, to aid in radiation therapy (RT) planning. ASSET was retrospectively applied to CTs for 26 thoracic RT patients (13 undergoing VT ablation). The physician-defined parasternal long-axis of the left ventricle (LV) and the axes generated from principal component analysis (PCA) were compared using mean distance to agreement (MDA) and angle of separation. The manually selected right ventricle insertion point and LVs …

Understanding Disruptions In Cancer Care To Reduce Increased Cancer Burden, Kia L Davis, Nicole Ackermann, Lisa M Klesges, Nora Leahy, Callie Walsh-Bailey, Sarah Humble, Bettina Drake, Vetta L Sanders Thompson

2020-Current year OA Pubs

BACKGROUND: This study seeks to understand how and for whom COVID-19 disrupted cancer care to understand the potential for cancer health disparities across the cancer prevention and control continuum.

METHODS: In this cross-sectional study, participants age 30+residing in an 82-county region in Missouri and Illinois completed an online survey from June-August 2020. Descriptive statistics were calculated for all variables separately and by care disruption status. Logistic regression modeling was conducted to determine the correlates of care disruption.

RESULTS: Participants (N=680) reported 21% to 57% of cancer screening or treatment appointments were canceled/postponed from March 2020 through the end of 2020. …

Rho Enhancers Play Unexpectedly Minor Roles In Rhodopsin Transcription And Rod Cell Integrity, Chi Sun, Philip A Ruzycki, Shiming Chen

2020-Current year OA Pubs

Enhancers function with a basal promoter to control the transcription of target genes. Enhancer regulatory activity is often studied using reporter-based transgene assays. However, unmatched results have been reported when selected enhancers are silenced in situ. In this study, using genomic deletion analysis in mice, we investigated the roles of two previously identified enhancers and the promoter of the Rho gene that codes for the visual pigment rhodopsin. The Rho gene is robustly expressed by rod photoreceptors of the retina, and essential for the subcellular structure and visual function of rod photoreceptors. Mutations in RHO cause severe vision loss in …

A Comprehensive Report Of Intrinsically Disordered Regions In Inherited Retinal Diseases, Karen E Lee, Jose S Pulido, Mariana M Da Palma, Rebecca Procopio, Robert B Hufnagel, Margaret Reynolds

2020-Current year OA Pubs

BACKGROUND/PURPOSE: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated.

METHODS: IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder.

MAIN OUTCOME MEASURES: The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent …

Association Of Social Deprivation With Survival In Younger Adult Patients With Aml: An Alliance Study, Melanie Rebechi, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

No abstract provided.

Clonal Hematopoiesis In Survivors Of Childhood Cancer, Danielle Novetsky Friedman, Irenaeus C C Chan, Kimberly Turner, Jie Liu, Megan A Cooper, Iskra Pusic, Geoffrey Uy, Daniel Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

No abstract provided.

Influenza Vaccine Format Mediates Distinct Cellular And Antibody Responses In Human Immune Organoids, Jenna M Kastenschmidt, Elizabeth Levendosky, Naresha Saligrama, Et Al.

2020-Current year OA Pubs

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, we sought to understand how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in their magnitude, diversity, phenotype, function, and breadth. These differences culminated …

Statin Use In Myelodysplastic Syndromes Is Associated With A Better Survival And Decreased Progression To Leukemia, Amber Afzal, Mark A Fiala, Meagan A Jacoby, Matthew J Walter

2020-Current year OA Pubs

No abstract provided.

Influence Of Participant And Reviewer Characteristics In Application Scores For A Hematology Research Training Program, Sara K Vesely, Allison King, Emily Vettese, John G Heller, Adam Cuker, Cecelia Calhoun, Wendy Stock, Morgan Homer, Josel Fritz, Lillian Sung

2020-Current year OA Pubs

The American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. …