Medicine and Health Sciences Commons^™

Rapidplan Hippocampal Sparing Whole Brain Model Version 2-How Far Can We Reduce The Dose?, Hefei Liu, Ryan Clark, Anthony Magliari, Robert Foster, Francisco Reynoso, Matthew Schmidt, Vinai Gondi, Christopher Abraham, Heather Curry, Patrick Kupelian, Deepak Khuntia, Sushil Beriwal

2020-Current year OA Pubs

Whole-brain radiotherapy has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics. Forty-two clinical cases were contoured according to guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive …

Clinical Trial Data Of Anti-Pd-1/Pd-L1 Therapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma: A Review, Douglas R Adkins, Robert I. Haddad

2020-Current year OA Pubs

IMPORTANCE: Anti-programmed cell death receptor-1 (PD-1) therapy is standard of care for incurable recurrent or metastatic non-nasopharyngeal head and neck cancer. In contrast, there are no regulatory agency-approved anti-PD-1 agents indicated for the treatment of recurrent or metastatic nasopharyngeal carcinomas (RM-NPC) in the Western hemisphere, and no standard treatment option exists beyond first-line chemotherapy for RM-NPC. The pace of development of novel systemic therapy regimens for RM-NPC has been slow compared to many other advanced tumor types, leaving an unmet clinical need for these patients with a poor prognosis.

OBSERVATIONS: Recent clinical trials have documented the clinical activity of anti-PD-1 …

Pharmacophore Modeling For Biological Targets With High Flexibility: Lxrβ Case Study, Sophia Kchouk, Lamees Hegazy

2020-Current year OA Pubs

No abstract provided.

Updated Diagnostic Criteria And Nomenclature For Neurofibromatosis Type 2 And Schwannomatosis: An International Consensus Recommendation, Scott R Plotkin, David H Gutmann, Et Al.

2020-Current year OA Pubs

PURPOSE: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging.

METHODS: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups.

RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their …

Perspectives Of Participation In Daily Life From Cancer Survivors: A Qualitative Analysis, Allison J L'Hotta, Nirmala Shivakumar, Kathleen D Lyons, Audrey Trebelhorn, Annamayil Manohar, Allison A King

2020-Current year OA Pubs

OBJECTIVE: To characterize how survivors of cancer define participation.

DESIGN: Cross-sectional qualitative study.

SETTING: Participants were enrolled from a large academic medical center in the Midwestern United States. Interviews were conducted over Zoom or phone.

PARTICIPANTS: Survivors of cancer (N=40) with brain, breast, colorectal, or lung cancer (n=10 per group). Participants were purposively sampled to maximize variation in the study sample. Participant ages ranged from 26-83 years, with a mean age of 55 years. Seventy percent of participants were receiving active cancer treatment at the time of the interview.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participant perspectives gathered from 1-on-1 …

Adolescent And Young Adult Preferences For Financial Incentives To Support Adherence To Antiretroviral Therapy In Kenya: A Mixed Methods Study, Ingrid Eshun-Wilson, Eliud Akama, Fridah Adhiambo, Zachary Kwena, Bertha Oketch, Sarah Obatsa, Sarah Iguna, Jayne L Kulzer, James Nyanga, Everlyne Nyandieka, Ally Scheve, Elvin H Geng, Elizabeth A Bukusi, Lisa Abuogi

2020-Current year OA Pubs

INTRODUCTION: To develop a patient-centred financial incentive delivery strategy to improve antiretroviral treatment adherence in adolescents and young adults (AYA) living with HIV in Kisumu, Kenya, we conducted a mixed methods study exploring preferences.

METHODS: A discrete choice experiment (DCE) and focus group discussion (FGD) were conducted simultaneously to identify preferences for five incentive delivery strategy features: value, eligibility, recipient, format and disbursement frequency. We used consecutive sampling to recruit AYA (14-24 years) living with HIV attending three health facilities in Kisumu, Kenya. We calculated mean preferences, willingness to trade, latent class membership and predictors of latent class membership. The …

An Ips-Derived In Vitro Model Of Human Atrial Conduction, Sherri M Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo-Chan Weng, Jon Silva, Timothy W Smith, Stacey L Rentschler, Steven C George

2020-Current year OA Pubs

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of …

A Randomized Controlled Trial In Schools Aimed At Exploring Mechanisms Of Change Of A Multifaceted Implementation Strategy For Promoting Mental Health At The Workplace, Lydia Kwak, Anna Toropova, Byron J Powell, Rebecca Lengnick-Hall, Irene Jensen, Gunnar Bergström, Liselotte Schäfer Elinder, Kjerstin Stigmar, Charlotte Wåhlin, Christina Björklund

2020-Current year OA Pubs

BACKGROUND: This study will explore implementation mechanisms through which a single implementation strategy and a multifaceted implementation strategy operate to affect the implementation outcome, which is fidelity to the Guideline For The Prevention of Mental Ill Health within schools. The guideline gives recommendations on how workplaces can prevent mental ill health among their personnel by managing social and organizational risks factors in the work environment. Schools are chosen as the setting for the study due to the high prevalence of mental ill health among teachers and other personnel working in schools. The study builds on our previous research, in which …

Wolf's Isotopic Response Of Lichen Planus Following Contact Dermatitis, Bruin Pollard, William H Mccoy Iv, Craig L Leonardi, Ann G Martin

2020-Current year OA Pubs

No abstract provided.

Mild Hypothermia Fails To Protect Infant Macaques From Brain Injury Caused By Prolonged Exposure To Antiseizure Drugs, Chrysanthy Ikonomidou, Sophie H Wang, Nicole A Fuhler, Shreya Larson, Saverio Capuano 3rd, Kevin R Brunner, Kristin Crosno, Heather A Simmons, Andres F Mejia, Kevin K Noguchi

2020-Current year OA Pubs

Barbiturates and benzodiazepines are GABA

The Nepenthesin Insert In The Plasmodium Falciparum Aspartic Protease Plasmepsin V Is Necessary For Enzyme Function, Alexander J Polino, Justin J Miller, Soumendranath Bhakat, Sumit Mukherjee, Suhas Bobba, Gregory R Bowman, Daniel E Goldberg

2020-Current year OA Pubs

Plasmepsin V (PM V) is a pepsin-like aspartic protease essential for growth of the malarial parasite Plasmodium falciparum. Previous work has shown PM V to be an endoplasmic reticulum-resident protease that processes parasite proteins destined for export into the host cell. Depletion or inhibition of the enzyme is lethal during asexual replication within red blood cells as well as during the formation of sexual stage gametocytes. The structure of the Plasmodium vivax PM V has been characterized by X-ray crystallography, revealing a canonical pepsin fold punctuated by structural features uncommon to secretory aspartic proteases; however, the function of this unique …

A Mid-Level Health Manager Intervention To Promote Uptake Of Isoniazid Preventive Therapy Among People With Hiv In Uganda: A Cluster Randomised Trial, Elijah Kakande, Elvin H Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.

METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control …

The Transition To Parenthood In Obstetrics: Enhancing Prenatal Care For 2-Generation Impact, Catherine Monk, Sona Dimidjian, Ellen Galinsky, Kimberly D. Gregory, M. Camille Hoffman, Elizabeth A. Howell, Emily S. Miller, Cynthia Osborne, Cynthia E. Rogers, Darby E. Saxbe, Mary E. D'Alton

2020-Current year OA Pubs

Obstetrics, the specialty overseeing infant and parent health before birth, could be expanded to address the interrelated areas of parents' prenatal impact on children's brain development and their own psychosocial needs during a time of immense change and neuroplasticity. Obstetrics is primed for the shift that is happening in pediatrics, which is moving from its traditional focus on physical health to a coordinated, whole-child, 2- or multigeneration approach. Pediatric care now includes developmental screening, parenting education, parent coaching, access to developmental specialists, brain-building caregiving skills, linkages to community resources, and tiered interventions with psychologists. Drawing on decades of developmental origins …

Living With Cervical Spinal Cord Injury During The Covid-19 Pandemic: A Qualitative Study, Elspeth J R Hill, Allison J L'Hotta, Carie R Kennedy, Aimee S James, Ida K Fox

2020-Current year OA Pubs

OBJECTIVE: To understand how COVID-19 has affected the daily lives of people living with cervical spinal cord injury (SCI).

DESIGN: Cross sectional qualitative study.

SETTING: Academic medical center in the Midwestern United States.

PARTICIPANTS: Ten community-dwelling individuals (8 men, 2 women), average 11.6 years post-mid-cervical level SCI (N=10).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Semistructured interviews were completed by phone. The research team used thematic analysis and inductive strategies to analyze the data in this exploratory investigation.

RESULTS: People with cervical SCI living in the United States during the spring of 2020 experienced changes to their daily lives. Participants described …

Risk Factors For Shoulder Disorders Among French Workers: Prospective Cohort Study, Julie Bodin, Ronan Garlantézec, Alexis Descatha, Bradley Evanoff, Thierry Thomas, Yves Roquelaure

2020-Current year OA Pubs

OBJECTIVES: Shoulder disorders are common in the working population. This longitudinal study aimed to explore the relationships between personal factors and occupational organisational, psychosocial, and biomechanical factors and the incidence of shoulder disorders.

METHODS: A total of 3710 workers in the Pays de la Loire region (Loire Valley area, France) were randomly included by their occupational physician in the Cosali cohort between 2002 and 2005. All workers completed a self-administered questionnaire about personal factors and work exposure, and using a standardised physical examination, occupational physicians diagnosed shoulder disorders. Between 2007 and 2010, 1611 workers were re-examined by their occupational physician. …

A Narrative Review Of Irritable Bowel Syndrome With Diarrhea: A Primer For Primary Care Providers, Baha Moshiree, Joel J Heidelbaugh, Gregory S Sayuk

2020-Current year OA Pubs

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely diagnosis of IBS-D can be achieved easily using clinical criteria. Formal IBS diagnosis is important for optimizing treatment and patient outcomes and facilitating patient access to appropriate educational resources. Yet, given the symptom overlap with other gastrointestinal conditions, diagnosis of IBS-D often is perceived to be challenging. Treatment of IBS includes …

Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited …

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …

N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher

2020-Current year OA Pubs

Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. …

Impacts Of A Workplace-Based Weight-Control Intervention On Objective And Perceived Physical Activity Among A Subgroup Of Workers, Rachel Tabak, Ryan Colvin, Jaime R Strickland, Ann Marie Dale, Maura Kepper, Tara Ruggeri, Bradley Evanoff

2020-Current year OA Pubs

Physical activity (PA) has many benefits; however, groups facing barriers to health-promoting behaviors are less likely to be physically active. This may be addressed through workplace interventions. The current study employs objective (accelerometry) and perceived (International Physical Activity Questionnaire [IPAQ]) measures of PA among a subset of participants from the "Working for You" study, which tests a multi-level (work group and individual) workplace intervention targeted at workers with low-incomes. Linear mixed and hierarchical logistic regression models are used to determine the intervention's impact on moderate- to vigorous-PA (MVPA) and achieving the PA Guideline for Americans (≥150 minutes MVPA/week), respectively from …

High-Resolution Imaging Of Protein Secretion At The Single-Cell Level Using Plasmon-Enhanced Fluorodot Assay, Anushree Seth, Ekansh Mittal, Jingyi Luan, Samhitha Kolla, Monty B Mazer, Hemant Joshi, Rohit Gupta, Priya Rathi, Zheyu Wang, Jeremiah J Morrissey, Joel D Ernst, Cynthia Portal-Celhay, Sharon Celeste Morley, Jennifer A Philips, Srikanth Singamaneni

2020-Current year OA Pubs

Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of proteins secreted by single cells, to study cell-to-cell heterogeneity in secretion, or to detect proteins of low abundance or incipient secretion. Here, we introduce the "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging of protein secretion. We find that plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise compared with conventional fluorescence labels. We demonstrate high-resolution imaging of different secreted cytokines in the single-plexed and spectrally multiplexed FluoroDOT assay that revealed cellular heterogeneity in secretion of multiple proteins …

Cochlear Ribbon Synapse Maturation Requires Nlgn1 And Nlgn3, Miguel A Ramirez, Yuzuru Ninoyu, Cayla Miller, Leonardo R Andrade, Seby Edassery, Ewa Bomba-Warczak, Briana Ortega, Uri Manor, Mark A Rutherford, Rick A Friedman, Jeffrey N Savas

2020-Current year OA Pubs

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We report

Examining The Complementarity Between The Eric Compilation Of Implementation Strategies And The Behaviour Change Technique Taxonomy: A Qualitative Analysis, Sheena Mchugh, Justin Presseau, Courtney T Luecking, Byron J Powell

2020-Current year OA Pubs

BACKGROUND: Efforts to generate evidence for implementation strategies are frustrated by insufficient description. The Expert Recommendations for Implementing Change (ERIC) compilation names and defines implementation strategies; however, further work is needed to describe the actions involved. One potentially complementary taxonomy is the behaviour change techniques (BCT) taxonomy. We aimed to examine the extent and nature of the overlap between these taxonomies.

METHODS: Definitions and descriptions of 73 strategies in the ERIC compilation were analysed. First, each description was deductively coded using the BCT taxonomy. Second, a typology was developed to categorise the extent of overlap between ERIC strategies and BCTs. …

Human Induced Pluripotent Stem Cell Engineering Establishes A Humanized Mouse Platform For Pediatric Low-Grade Glioma Modeling, Corina Anastasaki, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne M Scheaffer, Amanda De Andrade Costa, Anna F Wilson, Chloe M Kernan, Ameera H Zafar, Xia Ge, Joel R Garbow, Fausto J Rodriguez, David H Gutmann

2020-Current year OA Pubs

A major obstacle to identifying improved treatments for pediatric low-grade brain tumors (gliomas) is the inability to reproducibly generate human xenografts. To surmount this barrier, we leveraged human induced pluripotent stem cell (hiPSC) engineering to generate low-grade gliomas (LGGs) harboring the two most common pediatric pilocytic astrocytoma-associated molecular alterations, NF1 loss and KIAA1549:BRAF fusion. Herein, we identified that hiPSC-derived neuroglial progenitor populations (neural progenitors, glial restricted progenitors and oligodendrocyte progenitors), but not terminally differentiated astrocytes, give rise to tumors retaining LGG histologic features for at least 6 months in vivo. Additionally, we demonstrated that hiPSC-LGG xenograft formation requires the absence …

Engineering Rotating Apical-Out Airway Organoid For Assessing Respiratory Cilia Motility, Piyumi Wijesekara, Prakarsh Yadav, Lydia A. Perkins, Donna B. Stolz, Jonathan M. Franks, Simon C. Watkins, Emily Reinoso Jacome, Steven L. Brody, Amjad Horani, Jian Xu, Amir Barati Farimani, Xi Ren

2020-Current year OA Pubs

Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Owing to cilia's nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) from a defined number of cells. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and correlated it with the direct measurement of cilia motility. We further established the feasibility of using AOAO …

Human Total, Basal And Activity Energy Expenditures Are Independent Of Ambient Environmental Temperature, Xueying Zhang, Susan B Racette, Et Al.

2020-Current year OA Pubs

Lower ambient temperature (T

Implementing Screening For Hypertension In Archetypal Hiv Primary Care: A Mixed-Methods Assessment, Lydia Buzaalirwa, Lydia Nambala, Grace Banturaki, Penninah Iutung Amor, Anne Katahoire, Elvin Geng, Aggrey Semeere

2020-Current year OA Pubs

BACKGROUND: High prevalence of HIV and hypertension in sub-Saharan Africa puts adults living with HIV (ALWH) at high risk of end-organ complications. Both World Health Organization (WHO) and national guidelines recommend screening and treatment of hypertension among ALWH on antiretroviral therapy (ART). We evaluated the implementation of hypertension screening among adults on ART at three Uganda Cares Primary care facilities.

METHODS: Using a sequential explanatory mixed-methods approach, we reviewed patient records, and interviewed both patients and providers during 2018 and 2019. We obtained demographics, clinical and blood pressure (BP) measurements via records review. We estimate the period prevalence of screening …

Delay Of Gratification Dissociates Cognitive Control And Valuation Brain Regions In Healthy Young Adults, Bidhan Lamichhane, Elisa Di Rosa, Todd S Braver

2020-Current year OA Pubs

Delay of gratification (DofG) refers to an inter-temporal choice phenomenon that is of great interest in many domains, including animal learning, cognitive development, economic decision-making, and executive control. Yet experimental tools for investigating DofG in human adults are almost non-existent, and as a consequence, very little is known regarding the brain basis of core DofG behaviors. Here, we utilize a novel DofG paradigm, adapted for use in neuroimaging contexts, to examine event-related changes in neural activity as healthy young adult participants made repeated choices to continue waiting for a delayed reward, rather than take an immediately available one of lesser …

Improving Our Understanding Of Driving Changes In Preclinical And Early Symptomatic Alzheimer's Disease: The Role Of Naturalistic Driving Studies, Catherine M Roe

2020-Current year OA Pubs

Research on how preclinical and early symptomatic Alzheimer's disease (AD) impacts driving behavior is in its infancy, with several important research areas yet to be explored. This paper identifies research gaps and suggests priorities for driving studies over the next few years among those at the earliest stages of AD. These priorities include how individual differences in demographic and biomarker measures of AD pathology, as well as differences in the in-vehicle and external driving environment, affect driving behavior. Understanding these differences is important to developing future interventions to increase driving safety among those at the earliest stages of AD.

A Scoping Review Of Frameworks In Empirical Studies And A Review Of Dissemination Frameworks, Ana A Baumann, Cole Hooley, Emily Kryzer, Alexandra B Morshed, Cassidy A Gutner, Sara Malone, Callie Walsh-Bailey, Meagan Pilar, Brittney Sandler, Rachel G Tabak, Stephanie Mazzucca

2020-Current year OA Pubs

BACKGROUND: The field of dissemination and implementation (D&I) research has grown immensely in recent years. However, the field of dissemination research has not coalesced to the same degree as the field of implementation research. To advance the field of dissemination research, this review aimed to (1) identify the extent to which dissemination frameworks are used in dissemination empirical studies, (2) examine how scholars define dissemination, and (3) identify key constructs from dissemination frameworks.

METHODS: To achieve aims 1 and 2, we conducted a scoping review of dissemination studies published in D&I science journals. The search strategy included manuscripts published from …