Medicine and Health Sciences Commons^™

Feasibility And Sensitivity Study Of Radiomic Features In Photoacoustic Imaging Of Patient-Derived Xenografts, Lorena Escudero Sanchez, Emma Brown, Leonardo Rundo, Stephan Ursprung, Evis Sala, Sarah E Bohndiek, Ignacio Xavier Partarrieu

2020-Current year OA Pubs

Photoacoustic imaging is an increasingly popular method of exploring the tumour microenvironment, which can provide insight into tumour oxygenation status and potentially treatment response assessment. Currently, the measurements most commonly performed on such images are the mean and median of the pixel values of the tumour volumes of interest. We investigated expanding the set of measurements that can be extracted from these images by adding radiomic features. In particular, we found that Skewness was sensitive to differences between basal and luminal patient derived xenograft cancer models with an [Formula: see text] of 0.86, and that it was robust to variations …

Effectiveness And Minimum Effective Dose Of App-Based Mobile Health Interventions For Anxiety And Depression Symptom Reduction: Systematic Review And Meta-Analysis, Sheng-Chieh Lu, Mindy Xu, Mei Wang, Angela Hardi, Abby L Cheng, Su-Hsin Chang, Po-Yin Yen

2020-Current year OA Pubs

BACKGROUND: Mobile health (mHealth) apps offer new opportunities to deliver psychological treatments for mental illness in an accessible, private format. The results of several previous systematic reviews support the use of app-based mHealth interventions for anxiety and depression symptom management. However, it remains unclear how much or how long the minimum treatment "dose" is for an mHealth intervention to be effective. Just-in-time adaptive intervention (JITAI) has been introduced in the mHealth domain to facilitate behavior changes and is positioned to guide the design of mHealth interventions with enhanced adherence and effectiveness.

OBJECTIVE: Inspired by the JITAI framework, we conducted a …

Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Mary F. Feitosa, Et Al

2020-Current year OA Pubs

No abstract provided.

Idiopathic Ventricular Fibrillation In A Previously Healthy Recreational Athlete, Caleb Norton, Daniel H Cooper, Gregory Ewald, Mustafa Husaini

2020-Current year OA Pubs

There are several clinical challenges in the survivor of sudden cardiac arrest (SCA), including ensuring that a comprehensive diagnostic evaluation has been performed and providing counseling on return to activity. We report a case of a highly conditioned athlete who presented following aborted SCA during exercise with a diagnosis of idiopathic ventricular fibrillation arrest. (

Multimodal Single Cell Sequencing Implicates Chromatin Accessibility And Genetic Background In Diabetic Kidney Disease Progression, Parker C Wilson, Yoshiharu Muto, Haojia Wu, Anil Karihaloo, Sushrut S Waikar, Benjamin D Humphreys

2020-Current year OA Pubs

The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess …

Concentrated Incarceration And The Public-Housing-To-Prison Pipeline In New York City Neighborhoods, Jay Holder, Ivan Calaff, Brett Maricque, Van C Tran

2020-Current year OA Pubs

Using public housing developments as a strategic site, our research documents a distinct pathway linking disadvantaged context to incarceration-the public-housing-to-prison pipeline. Focusing on New York City Housing Authority (NYCHA) housing developments as a case study, we find that incarceration rates in NYCHA tracts are 4.6 times higher than those in non-NYCHA tracts. More strikingly, 94% of NYCHA tracts report rates above the median value for non-NYCHA tracts. Moreover, 17% of New York State's incarcerated population originated from just 372 NYCHA tracts. Compared with non-NYCHA tracts, NYCHA tracts had higher shares of Black residents and were significantly more disadvantaged. This NYCHA …

Issues With Variability In Electronic Health Record Data About Race And Ethnicity: Descriptive Analysis Of The National Covid Cohort Collaborative Data Enclave, Lily Cook, Juan Espinoza, Nicole G Weiskopf, Nisha Mathews, David A Dorr, Kelly L Gonzales, Adam Wilcox, Charisse Madlock-Brown, N3c Consoritium

2020-Current year OA Pubs

BACKGROUND: The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations.

OBJECTIVE: This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large …

Killer-Cell Immunoglobulin-Like Receptor Diversity In An Admixed South American Population, Marlon Castrillon, Nancy D Marin, Amado J Karduss-Urueta, Sonia Y Velasquez, Cristiam M Alvarez

2020-Current year OA Pubs

Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR).

Novel Antiinflammatory Biologics Shaped By Parasite-Host Coevolution, Stephanie M Ryan, Makedonka Mitreva, Et Al

2020-Current year OA Pubs

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of …

Smyd3 Impedes Small Cell Lung Cancer Sensitivity To Alkylation Damage Through Rnf113a Methylation-Phosphorylation Cross-Talk, Valentina Lukinović, Clement Oyeniran, Ning Tsao, Joshua R Brickner, Rebecca Rodell, Nima Mosammaparast, Et Al

2020-Current year OA Pubs

Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of …

An Ex Vivo Culture Model Of Kidney Podocyte Injury Reveals Mechanosensitive, Synaptopodin-Templating, Sarcomere-Like Structures, Shumeng Jiang, Farid Alisafaei, Yin-Yuan Huang, Yuan Hong, Xiangjun Peng, Chengqing Qu, Pongpratch Puapatanakul, Sanjay Jain, Jeffrey H Miner, Guy M Genin, Hani Y Suleiman

2020-Current year OA Pubs

Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte …

Lrp1 Is A Neuronal Receptor For Α-Synuclein Uptake And Spread, Kai Chen, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The aggregation and spread of α-synuclein (α-Syn) protein and related neuronal toxicity are the key pathological features of Parkinson's disease (PD) and Lewy body dementia (LBD). Studies have shown that pathological species of α-Syn and tau can spread in a prion-like manner between neurons, although these two proteins have distinct pathological roles and contribute to different neurodegenerative diseases. It is reported that the low-density lipoprotein receptor-related protein 1 (LRP1) regulates the spread of tau proteins; however, the molecular regulatory mechanisms of α-Syn uptake and spread, and whether it is also regulated by LRP1, remain poorly understood.

METHODS: We established …

The Metabolism Of Human Soluble Amyloid Precursor Protein Isoforms Is Quantifiable By A Stable Isotope Labeling-Tandem Mass Spectrometry Method, Justyna A Dobrowolska Zakaria, Randall J Bateman, Monika Lysakowska, Ammaarah Khatri, Dinorah Jean-Gilles, Matthew E Kennedy, Robert Vassar

2020-Current year OA Pubs

Evidence suggests that β-secretase (BACE1), which cleaves Amyloid Precursor Protein (APP) to form sAPPβ and amyloid-β, is elevated in Alzheimer's disease (AD) brains and biofluids and, thus, BACE1 is a therapeutic target for this devastating disease. The direct product of BACE1 cleavage of APP, sAPPβ, serves as a surrogate marker of BACE1 activity in the central nervous system. This biomarker could be utilized to better understand normal APP processing, aberrant processing in the disease setting, and modulations to processing during therapeutic intervention. In this paper, we present a method for measuring the metabolism of sAPPβ and another APP proteolytic product, …

Genome Scanning Of Behavioral Selection In A Canine Olfactory Detection Breeding Cohort, Alexander W Eyre, Isain Zapata, Elizabeth Hare, Katharine M N Lee, Claire Bellis, Jennifer L Essler, Cynthia M Otto, James A Serpell, Carlos E Alvarez

2020-Current year OA Pubs

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration's (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed …

Exit Rates Of Accountable Care Organizations That Serve High Proportions Of Beneficiaries Of Racial And Ethnic Minority Groups, Sunny C Lin, Karen E Joynt Maddox, Andrew M Ryan, Nicholas Moloci, Addison Shay, John Malcolm Hollingsworth

2020-Current year OA Pubs

Importance: The Medicare Shared Savings Program provides financial incentives for accountable care organizations (ACOs) to reduce costs of care. The structure of the shared savings program may not adequately adjust for challenges associated with caring for patients with high medical complexity and social needs, a population disproportionately made up of racial and ethnic minority groups. If so, ACOs serving racial and ethnic minority groups may be more likely to exit the program, raising concerns about the equitable distribution of potential benefits from health care delivery reform efforts.

Objective: To evaluate whether ACOs with a high proportion of beneficaries of racial …

Overall Survival In The Simplify-1 And Simplify-2 Phase 3 Trials Of Momelotinib In Patients With Myelofibrosis, Ruben Mesa, Stephen T Oh, Et Al

2020-Current year OA Pubs

Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS …

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 …

Real-Time Analysis And Display Of Quantitative Measures To Track And Improve Clinical Workflow, Reshma Munbodh, Toni M Roth, Kara L Leonard, Robert C Court, Utkarsh Shukla, Sarah Andrea, Marissa Gray, Gregg Leichtman, Eric E Klein

2020-Current year OA Pubs

PURPOSE: Radiotherapy treatment planning is a complex process with multiple, dependent steps involving an interdisciplinary patient care team. Effective communication and real-time tracking of resources and care path activities are key for clinical efficiency and patient safety.

MATERIALS AND METHODS: We designed and implemented a secure, interactive web-based dashboard for patient care path, clinical workflow, and resource utilization management. The dashboard enables visualization of resource utilization and tracks progress in a patient's care path from the time of acquisition of the planning CT to the time of treatment in real-time. It integrates with the departmental electronic medical records (EMR) system …

Risk Factors And Medical Resource Utilization In Us Adults Hospitalized With Influenza Or Respiratory Syncytial Virus In The Hospitalized Acute Respiratory Tract Infection Study, Jessica Hartnett, Prina Donga, Gabriela Ispas, Yannick Vandendijck, David Anderson, Stacey House, Selim Suner

2020-Current year OA Pubs

BACKGROUND: Influenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.

METHODS: HARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017-2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post-discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, …

Does Social Intolerance Vary According To Cognitive Styles, Genetic Cognitive Capacity, Or Education?, Aino Saarinen, Liisa Keltikangas-Järvinen, Henrik Dobewall, C Robert Cloninger, Ari Ahola-Olli, Terho Lehtimäki, Nina Hutri-Kähönen, Olli Raitakari, Suvi Rovio, Niklas Ravaja

2020-Current year OA Pubs

BACKGROUND: Low education, low cognitive abilities, and certain cognitive styles are suggested to predispose to social intolerance and prejudices. Evidence is, however, restricted by comparatively small samples, neglect of confounding variables and genetic factors, and a narrow focus on a single sort of prejudice. We investigated the relationships of education, polygenic cognitive potential, cognitive performance, and cognitive styles with social intolerance in adulthood over a 15-year follow-up.

METHODS: We used data from the prospective population-based Young Finns Study (n = 960-1679). Social intolerance was evaluated with the Social Intolerance Scale in 1997, 2001, and 2011; cognitive performance with the Cambridge …

Sex Differences In Wild-Type Transthyretin Amyloidosis: An Analysis From The Transthyretin Amyloidosis Outcomes Survey (Thaos), Courtney M Campbell, Samantha Lorusso, Angela Dispenzieri, Arnt V Kristen, Mathew S Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo Garcia-Pavia, Martha Grogan, Doug Chapman, Leslie Amass, Thaos Investigators

2020-Current year OA Pubs

INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

METHODS: THAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021).

RESULTS: Of 1386 patients with ATTRwt …

Exposure Contrasts Of Pregnant Women During The Household Air Pollution Intervention Network Randomized Controlled Trial, Michael Johnson, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to

OBJECTIVES: This paper reports exposure reductions achieved by a liquified petroleum gas (LPG) stove and fuel intervention for pregnant mothers in the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial.

METHODS: The HAPIN trial included 3,195 households primarily using biomass for cooking in Guatemala, India, Peru, and Rwanda. Twenty-four-hour exposures to

RESULTS: Median postrandomization exposures of particulate matter (PM) with aerodynamic diameter

DISCUSSION: Postintervention

Association Of Male Hypogonadism With Risk Of Hospitalization For Covid-19, Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan

2020-Current year OA Pubs

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh).

Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh.

Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021.

Exposures: The primary exposure was gonadal status …

Association Of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest, Ericka L Fink, Stuart Friess, Et Al.

2020-Current year OA Pubs

Importance: Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment.

Objective: To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest.

Design, Setting, and Participants: The Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included …

Minimal Change Prion Retinopathy: Morphometric Comparison Of Retinal And Brain Prion Deposits In Creutzfeldt-Jakob Disease, Vanessa S Goodwill, Ian Dryden, Jihee Choi, Chiara De Lillo, Katrin Soldau, Jorge Llibre-Guerra, Henry Sanchez, Christina J Sigurdson, Jonathan H Lin

2020-Current year OA Pubs

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrP

Creation And Internal Validation Of A Clinical Predictive Model For Fluconazole Resistance In Patients With Candida Bloodstream Infection, Adriana M Rauseo, Margaret A Olsen, Dustin Stwalley, Patrick B Mazi, Lindsey Larson, William G Powderly, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: Fluconazole is recommended as first-line therapy for candidemia when risk of fluconazole resistance (fluc-R) is low. Lack of methods to estimate resistance risk results in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial or early step-down fluconazole would be appropriate.

METHODS: Retrospective analysis of hospitalized adult patients with positive blood culture for

RESULTS: We identified 539 adults with candidemia and 72

CONCLUSIONS: This model is a potential tool for identifying patients at low risk for fluc-R candidemia to receive first-line or …

Methylation-Mediated Silencing Of Ptprd Induces Pulmonary Hypertension By Promoting Pulmonary Arterial Smooth Muscle Cell Migration Via The Pdgfrb/Plcγ1 Axis, Junhua Xu, Yanfeng Zhong, Haoyang Yin, John Linneman, Yixuan Luo, Sijian Xia, Qinyi Xia, Lei Yang, Xingtao Huang, Kang Kang, Jun Wang, Yanqin Niu, Li Li, Deming Gou

2020-Current year OA Pubs

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension.

METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia.

RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary …

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.

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 …

World Guidelines For Falls Prevention And Management For Older Adults: A Global Initiative, Manuel Montero-Odasso, Susan Stark, Et Al.

2020-Current year OA Pubs

No abstract provided.