Medicine and Health Sciences Commons^™

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population, Elias S Sotirchos, Robert T Naismith, Min Qiao, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

Sting Suppresses Mitochondrial Vdac2 To Govern Rcc Growth Independent Of Innate Immunity, Zhichuan Zhu, Xin Zhou, Hongwei Du, Erica W Cloer, Jiaming Zhang, Liu Mei, Ying Wang, Xianming Tan, Austin J Hepperla, Jeremy M Simon, Jeanette Gowen Cook, Michael B Major, Gianpietro Dotti, Pengda Liu

2020-Current year OA Pubs

STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth …

The Plasma Virome In Longitudinal Samples From Pregnant Patients, Molly J Stout, Anoop K Brar, Brandi N Herter, Ananda Rankin, Kristine M Wylie

2020-Current year OA Pubs

INTRODUCTION: Nucleic acid from viruses is common in peripheral blood, even in asymptomatic individuals. How physiologic changes of pregnancy impact host-virus dynamics for acute, chronic, and latent viral infections is not well described. Previously we found higher viral diversity in the vagina during pregnancy associated with preterm birth (PTB) and Black race. We hypothesized that higher diversity and viral copy numbers in the plasma would show similar trends.

METHODS: To test this hypothesis, we evaluated longitudinally collected plasma samples from 23 pregnant patients (11 term and 12 preterm) using metagenomic sequencing with ViroCap enrichment to enhance virus detection. Sequence data …

Review Of Factors Resulting In Systemic Biases In The Screening, Assessment, And Treatment Of Individuals At Clinical High-Risk For Psychosis In The United States, Miranda A Bridgwater, Emily Petti, Maksim Giljen, Leeann Akouri-Shan, Joseph S Deluca, Pamela Rakhshan Rouhakhtar, Caroline Millar, Nicole R Karcher, Elizabeth A Martin, Jordan Devylder, Deidre Anglin, Raquel Williams, Lauren M Ellman, Vijay A Mittal, Jason Schiffman

2020-Current year OA Pubs

BACKGROUND: Since its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature.

RESULTS: Existing literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender …

3′-Sulfated Lewisa/C: An Oncofetal Epitope Associated With Metaplastic And Oncogenic Plasticity Of The Gastrointestinal Foregut, Koushik K Das, Jeffrey W Brown

2020-Current year OA Pubs

Metaplasia, dysplasia, and cancer arise from normal epithelia

A Practitioner's Guide To Geospatial Analysis In A Neuroimaging Context, Julie K Wisch, Ganesh M Babulal, Kalen Petersen, Peter R Millar, Enbal Shacham, Stephen Scroggins, Anna H Boerwinkle, Shaney Flores, Sarah Keefe, Brian A Gordon, John C Morris, Beau M Ances

2020-Current year OA Pubs

INTRODUCTION: Health disparities arise from biological-environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort.

METHODS: We estimated brain age gap (BAG) from structural magnetic resonance imaging (MRI) from 239 city-dwelling participants in St. Louis, Missouri. We compared these participants to population-level estimates from the American Community Survey (ACS). We used geospatial analysis to identify neighborhoods associated with patterns of altered brain structure. We also evaluated the relationship between Area Deprivation Index (ADI) and BAG.

RESULTS: …

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

The In Vivo Study Of Cardiac Mechano-Electric And Mechano-Mechanical Coupling During Heart Development In Zebrafish, Jonathan S Baillie, Alex Gendernalik, Deborah M Garrity, David Bark Jr, T Alexander Quinn

2020-Current year OA Pubs

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

A Review Of Technological Innovations Leading To Modern Endovascular Brain Aneurysm Treatment, David C Lauzier, Anna L Huguenard, Anja I Srienc, Samuel J Cler, Joshua W Osbun, Arindam R Chatterjee, Ananth K Vellimana, Akash P Kansagra, Colin P Derdeyn, Dewitte T Cross, Christopher J Moran

2020-Current year OA Pubs

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.

Precision Neuromodulation: Promises And Challenges Of Spinal Stimulation For Multi-Modal Rehabilitation, Maria F Bandres, Jefferson L Gomes, Gerson N Moreno Romero, Avery R Twyman, Jacob Graves Mcpherson

2020-Current year OA Pubs

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar …

The Function Of Histone Methylation And Acetylation Regulators In Gbm Pathophysiology, Colin Mccornack, Timothy Woodiwiss, Angela Hardi, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In …

Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent …

Down Syndrome And Alzheimer's Disease: A Scoping Review Of Functional Performance And Fall Risk, Selena E Washington, Emily Cler, Cameron Lowery, Susan L Stark

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and …

Genotype And Clinical Characteristics Of Patients With Wolfram Syndrome And Wfs1-Related Disorders, Evan M Lee, Megha Verma, Nila Palaniappan, Emiko M Pope, Sammie Lee, Lindsey Blacher, Pooja Neerumalla, William An, Toko Campbell, Cris Brown, Stacy Hurst, Bess Marshall, Tamara Hershey, Fumihiko Urano, Et Al.

2020-Current year OA Pubs

No abstract provided.

Financial Burden Of Men With Localized Prostate Cancer: A Process Paper, Ashley J Housten, Hannah E Rice, Su-Hsin Chang, Allison J L'Hotta, Eric H Kim, Bettina F Drake, Robin Wright-Jones, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Many individuals undergoing cancer treatment experience substantial financial hardship, often referred to as financial toxicity (FT). Those undergoing prostate cancer treatment may experience FT and its impact can exacerbate disparate health outcomes. Localized prostate cancer treatment options include: radiation, surgery, and/or active surveillance. Quality of life tradeoffs and costs differ between treatment options. In this project, our aim was to quantify direct healthcare costs to support patients and clinicians as they discuss prostate cancer treatment options. We provide the transparent steps to estimate healthcare costs associated with treatment for localized prostate cancer among the privately insured population using a …

The Evaluation Of The Delayed Swollen Breast In Patients With A History Of Breast Implants, Grace C Keane, Alexandra M Keane, Ryan Diederich, Kaitlyn Kennard, Eric J Duncavage, Terence M Myckatyn

2020-Current year OA Pubs

Breast implants, whether placed for reconstructive or cosmetic purposes, are rarely lifetime devices. Rupture, resulting from compromised implant shell integrity, and capsular contracture caused by constriction of the specialized scar tissue that normally forms around breast implants, have long been recognized, and remain the leading causes of implant failure. It is apparent, however, that women with breast implants may also experience delayed breast swelling due to a range of etiologic factors. While a majority of delayed seromas associated with breast implants have a benign etiology, this presentation cannot be ignored without an adequate workup as malignancies such as breast implant …

Changes In Patient-Reported Pain Interference After Surgical Treatment Of Painful Lower Extremity Neuromas, Adam Liebendorfer, Esther Ochoa, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Painful neuromas commonly cause neuropathic pain, in up to 1 in 20 cases of traumatic or iatrogenic nerve injury. Despite the multiple surgical treatment types that reduce pain, no type has been universally accepted.

METHODS: We performed a retrospective cohort study by administering follow-up surveys to all surgical patients treated in our department for lower-extremity neuroma from September 1, 2015, to October 22, 2021, that could be contacted, excluding those with Morton neuroma. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) questionnaire, survey questions covered the time to pain reduction, use of physical or …

A Universal Neocortical Mask For Centiloid Quantification, Pierrick Bourgeat, Vincent Doré, Christopher C Rowe, Tammie Benzinger, Duygu Tosun, Manu S Goyal, Pamela Lamontagne, Liang Jin, Michael W Weiner, Colin L Masters, Jurgen Fripp, Victor L Villemagne, Alzheimer's Disease Neuroimaging Initiative; Oasis3, Aibl Research Group

2020-Current year OA Pubs

INTRODUCTION: The Centiloid (CL) project was developed to harmonize the quantification of amyloid beta (Aβ) positron emission tomography (PET) scans to a unified scale. The CL neocortical mask was defined using

METHODS: Using data from the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) study (Australian Imaging Biomarkers and Lifestyle + Alzheimer's Disease Neuroimaging Initiative + Open Access Series of Imaging Studies), age-matched pairs of mild Alzheimer's disease (AD) and healthy controls (HC) were selected:

RESULTS: In the GAAIN dataset, the universal mask led to a small reduction in the variance of the YC, and a small increase in …

Conditional Protein Degradation In Yarrowia Lipolytica Using The Auxin-Inducible Degron, Zhenlin Han, Jessica Maruwan, Yinjie Tang, Wei Wen Su

2020-Current year OA Pubs

Conditional protein degradation is a powerful tool for controlled protein knockdown. The auxin-inducible degron (AID) technology uses a plant auxin to induce depletion of degron-tagged proteins, and it has been shown to be functional in several non-plant eukaryotes. In this study, we demonstrated AID-based protein knockdown in an industrially important oleaginous yeast

Carotid Atherosclerotic Plaque Segmentation In Multi-Weighted Mri Using A Two-Stage Neural Network: Advantages Of Training With High-Resolution Imaging And Histology, Ran Li, Jie Zheng, Mohamed A Zayed, Jeffrey E Saffitz, Pamela K Woodard, Abhinav K Jha

2020-Current year OA Pubs

INTRODUCTION: A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes.

METHODS: To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that …

Ube2c Expression Is Elevated In Hepatoblastoma And Correlates With Inferior Patient Survival, Ruth Nousiainen, Katja Eloranta, Noora Isoaho, Stefano Cairo, David B Wilson, Markku Heikinheimo, Marjut Pihlajoki

2020-Current year OA Pubs

Hepatoblastoma (HB) is the most common malignant liver tumor among children. To gain insight into the pathobiology of HB, we performed RNA sequence analysis on 5 patient-derived xenograft lines (HB-243, HB-279, HB-282, HB-284, HB-295) and 1 immortalized cell line (HUH6). Using cultured hepatocytes as a control, we found 2,868 genes that were differentially expressed in all of the HB lines on mRNA level. The most upregulated genes were

Proceedings Of The Association For Pathology Informatics Bootcamp 2022, Amrom E Obstfeld, Victor Brodsky, Alexis B Carter, Peter Gershkovich, Shannon Haymond, Bruce Levy, John Sinard, Devereaux Sellers, Michelle Stoffel, Ronald Jackups

2020-Current year OA Pubs

The Pathology Informatics Bootcamp, held annually at the Pathology Informatics Summit, provides pathology trainees with essential knowledge in the rapidly evolving field of Pathology Informatics. With a focus on data analytics, data science, and data management in 2022, the bootcamp addressed the growing importance of data analysis in pathology and laboratory medicine practice. The expansion of data-related subjects in Pathology Informatics Essentials for Residents (PIER) and the Clinical Informatics fellowship examinations highlights the increasing significance of these skills in pathology practice in particular and medicine in general. The curriculum included lectures on databases, programming, analytics, machine learning basics, and specialized …

Patient Specific Contouring Region Of Interest For Abdominal Stereotactic Adaptive Radiotherapy, Alex T Price, Christopher J Zachary, Eric Laugeman, Borna Maraghechi, Tong Zhu, Lauren E Henke

2020-Current year OA Pubs

Contouring during adaptive radiotherapy (ART) can be a time-consuming process. This study describes the generation of patient specific contouring regions of interest (CRoI) for evaluating the high dose fall-off in stereotactic abdominal ART. An empirical equation was derived to determine the radius of a cylindrical patient specific CRoIs. These CRoIs were applied to 60 patients and their adaptive fractions (301 unique treatment plans). Out of the 301 unique treatment plans, 284 (94%) treatment plans contained the high dose fall-off within the CRoI. There was an expected predicted average timesaving of 2.9-min-per case. Patient specific CRoIs improves the efficiency of ART.

Transferrin Receptor In Primary And Metastatic Breast Cancer: Evaluation Of Expression And Experimental Modulation To Improve Molecular Targeting, Francesca Fontana, Alison K. Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S. Allen, Yalin Xu, Jennifer L. Davis, Ariel Gabay, Jingyu Xiang, Kristin A. Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher

2020-Current year OA Pubs

BACKGROUND: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.

METHODS: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were …

Maximizing Flow Rate In Single Paper Layer, Rapid Flow Microfluidic Paper-Based Analytical Devices, Iain Macleod Briongos, Zachary D Call, Charles S Henry, David L Bark Jr.

2020-Current year OA Pubs

UNLABELLED: Small, single-layer microfluidic paper-based analytical devices (µPADs) offer potential for a range of point-of-care applications; however, they have been limited to low flow rates. Here, we investigate the role of laser cutting paper channels in maximizing flow rate in small profile devices with limited fluid volumes. We demonstrate that branching, laser-cut grooves can provide a 59.23-73.98% improvement in flow rate over a single cut, and a 435% increase over paper alone. These design considerations can be applied to more complex microfluidic devices with the aim of increasing the flow rate, and could be used in stand-alone channels for self-pumping. …

The Oral Selective Estrogen Receptor Degrader Gdc-0810 (Arn-810) In Postmenopausal Women With Hormone Receptor-Positive Her2-Negative (Hr + /Her2 -) Advanced/Metastatic Breast Cancer, Aditya Bardia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

METHODS: A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

RESULTS: Patients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose …

Scaling-Up Child And Youth Mental Health Services: Assessing Coverage Of A County-Wide Prevention And Early Intervention Initiative During One Fiscal Year, Cole Hooley, Deborah Salvo, Derek S Brown, Lauren Brookman-Frazee, Anna S Lau, Ross C Brownson, Patrick J Fowler, Debbie Innes-Gomberg, Enola K Proctor

2020-Current year OA Pubs

PURPOSE: In the U.S., the percentage of youth in need of evidence-based mental health practices (EBPs) who receive them (i.e., coverage rate) is low. We know little about what influences coverage rates. In 2010, the Los Angeles County Department of Mental Health (LACDMH) launched a reimbursement-driven implementation of multiple EBPs in youth mental health care. This study examines two questions: (1) What was the coverage rate of EBPs delivered three years following initial implementation? (2) What factors are associated with the coverage rates?

METHODS: To assess coverage rates of publicly insured youth, we used LACDMH administrative claims data from July …

Introducing Sonhr-Reporting Guidelines For Social Networks In Health Research, Douglas A. Luke, Edward Tsai, Bobbi J. Carothers, Sara Malone, Beth Prusaczyk, Todd B. Combs, Mia T Vogel, Jennifer Watling Neal, Zachary P. Neal

2020-Current year OA Pubs

OBJECTIVE: The overall goal of this work is to produce a set of recommendations (SoNHR-Social Networks in Health Research) that will improve the reporting and dissemination of social network concepts, methods, data, and analytic results within health sciences research.

METHODS: This study used a modified-Delphi approach for recommendation development consistent with best practices suggested by the EQUATOR health sciences reporting guidelines network. An initial set of 28 reporting recommendations was developed by the author team. A group of 67 (of 147 surveyed) experienced network and health scientists participated in an online feedback survey. They rated the clarity and importance of …

Development Of A Social And Environmental Determinants Of Health Informatics Maturity Model, Juan C Espinoza, Shruti Sehgal, Jimmy Phuong, Neil Bahroos, Justin Starren, Adam Wilcox, Daniella Meeker

2020-Current year OA Pubs

INTRODUCTION: Integrating social and environmental determinants of health (SEDoH) into enterprise-wide clinical workflows and decision-making is one of the most important and challenging aspects of improving health equity. We engaged domain experts to develop a SEDoH informatics maturity model (SIMM) to help guide organizations to address technical, operational, and policy gaps.

METHODS: We established a core expert group consisting of developers, informaticists, and subject matter experts to identify different SIMM domains and define maturity levels. The candidate model (v0.9) was evaluated by 15 informaticists at a Center for Data to Health community meeting. After incorporating feedback, a second evaluation round …