Medicine and Health Sciences Commons^™

Complete Mapping Of Mutations To The Sars-Cov-2 Spike Receptor-Binding Domain That Escape Antibody Recognition, Allison J. Greaney, Paul W. Rothlauf, Zhuoming Liu, Sean P. J. Whelan, Et Al.

2020-Current year OA Pubs

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of …

Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son

2020-Current year OA Pubs

BACKGROUND: In this study, we investigated the relationship between clinicopathologic factors, BRAF

METHODS: From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAF

RESULTS: Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17-81) were included. The majority of patients had BRAF

CONCLUSION: The majority of recurrent or metastatic RAI-negative DTC have BRAF

Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor

2020-Current year OA Pubs

BACKGROUND: Group model building (GMB) is a method to facilitate shared understanding of structures and relationships that determine system behaviors. This project aimed to determine the feasibility of GMB in a resource-limited setting and to use GMB to describe key barriers and facilitators to effective acute care delivery at a tertiary care hospital in Malawi.

METHODS: Over 1 week, trained facilitators led three GMB sessions with two groups of healthcare providers to facilitate shared understanding of structures and relationships that determine system behaviors. One group aimed to identify factors that impact patient flow in the paediatric special care ward. The …

Context-Responsive Anticoagulation Reduces Complications In Pediatric Extracorporeal Membrane Oxygenation, John C Lin, Lauren M Barron, Adam M Vogel, Ryan M Colvin, Sirine A Baltagi, Allan Doctor, Avihu Z Gazit, Mary Mehegan, Nicole O'Connor, Ahmed S Said, Mark Shepard, Michael Wallendorf, Philip C Spinella

2020-Current year OA Pubs

No abstract provided.

The Genomics Of Heart Failure: Design And Rationale Of The Hermes Consortium, R. Thomas Lumbers, Douglas Mann, Et Al.

2020-Current year OA Pubs

No abstract provided.

Does Circulating Progesterone Mediate The Associations Of Single Nucleotide Polymorphisms In Progesterone Receptor (Pgr)-Related Genes With Mammographic Breast Density In Premenopausal Women?, Favour A Akinjiyan, Yunan Han, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

UNLABELLED: Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP …

A Phase Ii Study Of Laser Interstitial Thermal Therapy Combined With Doxorubicin In Patients With Recurrent Glioblastoma, Omar H Butt, Alice Y Zhou, Jiayi Huang, William A Leidig, Alice E Silberstein, Milan G Chheda, Tanner M Johanns, George Ansstas, Jingxia Liu, Grayson Talcott, Ruth Nakiwala, Joshua S Shimony, Albert H Kim, Eric C Leuthardt, Jian L Campian, Et Al.

2020-Current year OA Pubs

BACKGROUND: The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.

METHODS: Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared …

Going Remote: Implementing Digital Research Methods At An Academic Medical Center During Covid-19, Katie E Keenoy, Eric J Lenze, Ginger E Nicol

2020-Current year OA Pubs

COVID-19 has forced medical research institutions to conduct clinical research remotely. Here, we describe how a university's mHealth Research Core helped facilitate the shift to remote research during the COVID-19 pandemic. In 2019 (pre-pandemic), we conducted stakeholder interviews and leadership group sessions to identify, create, and implement resources and core functions to support investigator-initiated mHealth research. Between April 2019 and February 2020, we identified four investigator needs: 1) a

Differentiating Wide Complex Tachycardias: A Historical Perspective, Anthony H Kashou, Christopher M Evenson, Peter A Noseworthy, Thoddi R Muralidharan, Christopher V Desimone, Abhishek J Deshmukh, Samuel J Asirvatham, Adam M May

2020-Current year OA Pubs

One of the most critical and challenging skills is the distinction of wide complex tachycardias into ventricular tachycardia or supraventricular wide complex tachycardia. Prompt and accurate differentiation of wide complex tachycardias naturally influences short- and long-term management decisions and may directly affect patient outcomes. Currently, there are many useful electrocardiographic criteria and algorithms designed to distinguish ventricular tachycardia and supraventricular wide complex tachycardia accurately; however, no single approach guarantees diagnostic certainty. In this review, we offer an in-depth analysis of available methods to differentiate wide complex tachycardias by retrospectively examining its rich literature base - one that spans several decades.

Anabolic Resistance Of Muscle Protein Turnover Comes In Various Shapes And Sizes, Kevin J M Paulussen, Colleen F Mckenna, Joseph W Beals, Kenneth R Wilund, Amadeo F Salvador, Nicholas A Burd

2020-Current year OA Pubs

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and …

Loss Of Angiotensin Ii Type 2 Receptor Improves Blood Pressure In Elastin Insufficiency, Michelle Lin, Robyn A Roth, Beth A Kozel, Robert P Mecham, Carmen M Halabi

2020-Current year OA Pubs

There is ample evidence supporting a role for angiotensin II type 2 receptor (AT

Nonliteral Language Processing Across The Lifespan, Kathrin Rothermich, Cristal Giorio, Sharon Falkins, Lindsay Leonard, Angela Roberts

2020-Current year OA Pubs

Studies investigating the effects of aging on nonliteral language processing have mainly focused on one sensory modality, for example written vignettes. In the current study, we used a video-based task to examine the effect of healthy aging on social communication perception using a novel database called RISC (Relation Inference in Social Communication). By means of an online recruitment platform, we asked young, middle-aged, and older adults between the ages of 18 and 76 (N = 100) to evaluate videos of actors using different forms of literal and nonliteral language, such as sarcasm or teasing. The participants' task was to infer …

Development Of A Digital Toolkit To Improve Quality Of Life Of Patients With Systemic Lupus Erythematosus, Jerik Leung, Laura Kloos, Alfred H Kim, Elizabeth A Baker

2020-Current year OA Pubs

OBJECTIVE: The purpose of this manuscript is to detail development and initial usability testing of an e-toolkit designed to provide skills and knowledge around self-management behaviors for individuals living with systemic lupus erythematosus.

METHODS: Researchers worked with a steering committee of patients and providers to (1) develop a clickable prototype of an e-toolkit and (2) conduct alpha (individuals not affiliated with an academic clinic as patient or provider) and beta (individual patients with systemic lupus erythematosus as well as members of the clinic healthcare team and individuals who work in patient advocacy organizations) usability testing through semistructured interviews.

RESULTS: During …

Electrophysiological And Molecular Mechanisms Of Sinoatrial Node Mechanosensitivity, Daniel Turner, Chen Kang, Pietro Mesirca, Juan Hong, Matteo E Mangoni, Alexey V Glukhov, Rajan Sah

2020-Current year OA Pubs

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels …

Inhibition Of Nox1 Mitigates Blood Pressure Increases In Elastin Insufficiency, Angela Troia, Russell H Knutsen, Carmen M Halabi, Daniela Malide, Zu Xi Yu, Amanda Wardlaw-Pickett, Elise K Kronquist, Kit Man Tsang, Attila Kovacs, Robert P Mecham, Beth A Kozel

2020-Current year OA Pubs

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include the

Incidentally Found Rib Hemangioma: Case Report And Discussion Of Management, Deniz B. Morkan, Jason M. Gauthier, Daniel Kreisel, Varun Puri, Ruben G. Nava

2020-Current year OA Pubs

Rib hemangioma is a rare chest wall tumor for which few reports in the literature exist to help guide treatment. The clinical presentation, radiographic findings, and treatment strategies vary in the literature, with the majority of patients undergoing surgical resection to definitively rule out malignancy. Here, we report a 23-year-old woman with an incidentally discovered rib hemangioma, who had a history of migraines, during the workup of a severe headache refractory to medical treatment. Imaging revealed a solitary, expansile tumor arising from the posterior left third rib. Spinal magnetic resonance imaging (MRI) showed a fat-containing lesion with multiple vascular flow …

Crowdsourced Assessment Of Surgical Skill Proficiency In Cataract Surgery, Grace L Paley, Rebecca Grove, Tejas C Sekhar, Jack Pruett, Michael V Stock, Tony N Pira, Steven M Shields, Evan L Waxman, Bradley S Wilson, Mae O Gordon, Susan M Culican

2020-Current year OA Pubs

OBJECTIVE: To test whether crowdsourced lay raters can accurately assess cataract surgical skills.

DESIGN: Two-armed study: independent cross-sectional and longitudinal cohorts.

SETTING: Washington University Department of Ophthalmology.

PARTICIPANTS AND METHODS: Sixteen cataract surgeons with varying experience levels submitted cataract surgery videos to be graded by 5 experts and 300+ crowdworkers masked to surgeon experience. Cross-sectional study: 50 videos from surgeons ranging from first-year resident to attending physician, pooled by years of training. Longitudinal study: 28 videos obtained at regular intervals as residents progressed through 180 cases. Surgical skill was graded using the modified Objective Structured Assessment of Technical Skill (mOSATS). …

Exploring Intentional Medication Non-Adherence In Patients With Systemic Lupus Erythematosus: The Role Of Physician-Patient Interactions, Jerik Leung, Elizabeth A Baker, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: Medication non-adherence contributes to worse health outcomes among SLE patients. The underlying mechanisms that drive medication non-adherence are poorly understood. The purpose of this study was to explore possible mechanisms of medication non-adherence by eliciting patient experiences.

METHODS: Consented adult patients with ACR- or SLICC-classified SLE were recruited. Ten semi-structured interviews were conducted across six participants. Interviews were audio recorded, transcribed, and analysed using an iterative process. The findings were presented to an interactive public forum with SLE patients, family members and friends of patients, and health-care professionals to assess validity and for elaboration of the concepts developed.

RESULTS: …

Disease-Modifying Therapy Prescription Patterns In People With Multiple Sclerosis By Age, Yinan Zhang, Amber Salter, Shan Jin, William J Culpepper, Gary R Cutter, Mitchell Wallin, Olaf Stuve

2020-Current year OA Pubs

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for their ability to reduce disease activity, namely clinical relapses and signal changes on magnetic resonance imaging (MRI). Disease activity appears age dependent. Thus, the greatest benefit would be expected in younger people with MS (PwMS) whereas benefits in the elderly are uncertain.

METHODS: Real-world data were obtained from PwMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR).

RESULTS: 6948 PwMS were surveyed from NARCOMS, and the MSSR had 1719 participants. In younger adult PwMS …

Climate Change And Antibiotic Resistance: A Deadly Combination, Jason P Burnham

2020-Current year OA Pubs

Climate change is driven primarily by humanity's use of fossil fuels and the resultant greenhouse gases from their combustion. The effects of climate change on human health are myriad and becomingly increasingly severe as the pace of climate change accelerates. One relatively underreported intersection between health and climate change is that of infections, particularly antibiotic-resistant infections. In this perspective review, the aspects of climate change that have already, will, and could possibly impact the proliferation and dissemination of antibiotic resistance are discussed.

Perceived Barriers To Assessing Understanding And Appreciation Of Informed Consent In Clinical Trials: A Mixed-Method Study, Erin D Solomon, Jessica Mozersky, Kari Baldwin, Matthew P Wroblewski, Meredith V Parsons, Melody Goodman, James M Dubois

2020-Current year OA Pubs

INTRODUCTION: Participants and research professionals often overestimate how well participants understand and appreciate consent information for clinical trials, and experts often vary in their determinations of participant's capacity to consent to research. Past research has developed and validated instruments designed to assess participant understanding and appreciation, but the frequency with which they are utilized is unknown.

METHODS: We administered a survey to clinical researchers working with older adults or those at risk of cognitive impairment (

RESULTS: We found that using a validated assessment of consent is relatively uncommon, being used by only 44% of researchers who had an opportunity. …

Teaching For Implementation: A Framework For Building Implementation Research And Practice Capacity Within The Translational Science Workforce, Aaron L Leppin, Ana A Baumann, Maria E Fernandez, Brittany N Rudd, Kathleen R Stevens, David O Warner, Bethany M Kwan, Rachel C Shelton

2020-Current year OA Pubs

Implementation science offers a compelling value proposition to translational science. As such, many translational science stakeholders are seeking to recruit, teach, and train an implementation science workforce. The type of workforce that will make implementation happen consists of both implementation researchers and practitioners, yet little guidance exists on how to train such a workforce. We-members of the Advancing Dissemination and Implementation Sciences in CTSAs Working Group-present the Teaching For Implementation Framework to address this gap. We describe the differences between implementation researchers and practitioners and demonstrate what and how to teach them individually and in co-learning opportunities. We briefly comment …

Temozolomide Chronotherapy In Patients With Glioblastoma: A Retrospective Single-Institute Study, Anna R Damato, Jingqin Luo, Ruth G N Katumba, Grayson R Talcott, Joshua B Rubin, Erik D Herzog, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival.

METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox …

Immune Cell Analysis Of Pilocytic Astrocytomas Reveals Sexually Dimorphic Brain Region-Specific Differences In T-Cell Content, Jie Chen, Namita Sinha, Olivia Cobb, Collin Liu, Ayca Ersen, Joanna J Phillips, Tarik Tihan, David H Gutmann, Sonika Dahiya

2020-Current year OA Pubs

No abstract provided.

Profiles Of Hiv Care Disruptions Among Adult Patients Lost To Follow-Up In Zambia: A Latent Class Analysis, Aaloke Mody, Kombatende Sikombe, Laura K. Beres, Sandra Simbeza, Njekwa Mukamba, Ingrid Eshun-Wilson, Sheree Schwartz, Jake Pry, Nancy Padian, Charles B. Holmes, Carolyn Bolton-Moore, Izukanji Sikazwe, Elvin H. Geng

2020-Current year OA Pubs

BACKGROUND: Patients report varied barriers to HIV care across multiple domains, but specific barrier patterns may be driven by underlying, but unobserved, behavioral profiles.

METHODS: We traced a probability sample of patients lost to follow-up (>90 days late) as of July 31, 2015 from 64 clinics in Zambia. Among those found alive, we ascertained patient-reported reasons for care disruptions. We performed latent class analysis to identify patient subgroups with similar patterns of reasons reported and assessed the association between class membership and care status (ie, disengaged versus silently transferred to a new site).

RESULTS: Among 547 patients, we identified …

Health Disparities And Treatment Approaches In Portopulmonary Hypertension And Idiopathic Pulmonary Arterial Hypertension: An Analysis Of The Pulmonary Hypertension Association Registry, Hilary M Dubrock, Murali Chakinala, Et Al.

2020-Current year OA Pubs

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = …

Clinicopathologic Implications Of Complement Genetic Variants In Kidney Transplantation, Zhen Ren, Stephen J Perkins, Latisha Love-Gregory, John P Atkinson, Anuja Java

2020-Current year OA Pubs

Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as variants of uncertain significance (VUS). Clinical risk assessment of patients carrying a VUS remains challenging primarily due to a lack of functional information, especially in the context of multiple confounding factors in the setting of kidney transplantation. Our objective was to evaluate the clinicopathologic significance of genetic variants in TMA and C3G in a kidney transplant cohort. We used whole exome next-generation sequencing to analyze complement genes in 76 patients, comprising 60 patients with a TMA and …

The Free And Cued Selective Reminding Test Predicts Braak Stage, Ellen Grober, Qi Qi, Lynn Kuo, Jason Hassenstab, Richard J Perrin, Richard B Lipton

2020-Current year OA Pubs

BACKGROUND: The ultimate validation of a clinical marker for Alzheimer's disease (AD) is its association with AD neuropathology.

OBJECTIVE: To identify clinical measures that predict pathology, we evaluated the relationships of the picture version of the Free and Cued Selective Reminding Test (pFCSRT + IR), the Mini-Mental State Exam (MMSE), and the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) to Braak stage.

METHODS: 315 cases from the clinicopathologic series at the Knight Alzheimer's Disease Research Center were classified according to Braak stage. Boxplots of each predictor were compared to identify the earliest stage at which decline was observed and …

Unfriendly Fire: How The Tobacco Industry Is Destroying The Future Of Our Children, Andrew Bush, Thomas Ferkol, Et Al.

2020-Current year OA Pubs

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned …

Rethinking Immune Checkpoint Blockade: Beyond The T Cell, Xiuting Liu, Graham D Hogg, David G Denardo

2020-Current year OA Pubs

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune …