Digital Commons Network^™

Acute Symptoms Of Mild To Moderate Covid-19 Are Highly Heterogeneous Across Individuals And Over Time, Thomas L. Rodebaugh, Madelyn R. Frumkin, Angela M. Reiersen, Eric J. Lenze, Michael S. Avidan, J. Philip Miller, Jay F. Piccirillo, Charles F. Zorumski, Caline Mattar

Open Access Publications

Background: The symptoms of coronavirus disease 2019 (COVID-19) appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and to assess how symptom course predicts other symptom changes as well as clinical deterioration.

Methods: One hundred sixty-two participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because 9 participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles.

Results: Trajectories varied …

The Dystonia Coalition: A Multicenter Network For Clinical And Translational Studies, Gamze Kilic-Berkmen, Laura J Wright, Joel S Perlmutter, Cynthia Comella, Mark Hallett, Jan Teller, Sarah Pirio Richardson, David A Peterson, Carlos Cruchaga, Codrin Lungu, H A Jinnah

Open Access Publications

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition …

Predicting Alcohol Use Disorder Remission: A Longitudinal Multimodal Multi-Featured Machine Learning Approach, Sivan Kinreich, Vivia V. Mccutcheon, Jessica L. Bourdon, Andrey P. Anokhin, Kathleen K. Bucholz, Meredith W. Francis, Et Al.

Open Access Publications

No abstract provided.

Genomic And Neoantigen Evolution From Primary Tumor To First Metastases In Head And Neck Squamous Cell Carcinoma, Charles R. Schutt, Hua Sun, Jaya Sarin Pradhan, Yvonne Saenger, Jessica Ley, Douglas Adkins, Matthew Ingham, Li Ding, Brian A. Van Tine

Open Access Publications

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified …

Brain Volumetric Deficits In Mapt Mutation Carriers: A Multisite Study, Stephanie A. Chu, Nupur Ghoshal, Et Al

Open Access Publications

No abstract provided.

Blood Leukocytes Recapitulate Diabetogenic Peptide-Mhc-Ii Complexes Displayed In The Pancreatic Islets, Anthony N. Vomund, Cheryl F. Lichti, Orion J. Peterson, Ana Maria Arbelaez, Xiaoxiao Wan, Emil R. Unanue

Open Access Publications

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule (MHC-II) I-Ag7 and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of the insulin peptides from the pancreatic islets. The circulating leukocytes, …

Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human And Mouse Hosts, Bruce A Rosa, Caroline Snowden, John Martin, Kerstin Fischer, Jonah Kupritz, Ethiopia Beshah, Taniawati Supali, Lincoln Gankpala, Peter U Fischer, Joseph F Urban, Makedonka Mitreva

Open Access Publications

The human whipworm

The Impact Of Covid-19 On Dual-Physician Couples: A Disproportionate Burden On Women Physicians, Andrea Soares, Prashanth Thakker, Elena Deych, Shikha Jain, Rakhee K. Bhayani

Open Access Publications

No abstract provided.

4Β-Hydroxycholesterol Is A Prolipogenic Factor That Promotes Srebp1c Expression And Activity Through The Liver X Receptor, Ofer Moldavski, Peter-James H. Zushin, Charles A. Berdan, Robert J. Van Eijkeren, Xuntian Jiang, Mingxing Qian, Daniel S. Ory, Douglas F. Covey, Daniel K. Nomura, Andreas Stahl, Ethan J. Weiss, Roberto Zoncu

Open Access Publications

No abstract provided.

Neuroskeletal Effects Of Chronic Bioelectric Nerve Stimulation In Health And Diabetes, Alec T Beeve, Ivana Shen, Xiao Zhang, Kristann Magee, Ying Yan, Matthew R Macewan, Erica L Scheller

Open Access Publications

Background/Aims: Bioelectric nerve stimulation (eStim) is an emerging clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes.

Methods: To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and …

Cohort Study Protocol To Characterize The Incidence And Severity Of Neuropathic Pain In Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Chioma U. Odozor, Kristen Roles, Carrie Burk, Thomas Kannampallil, David B. Clifford, Jay F. Piccirillo, Simon Haroutounian

Open Access Publications

No abstract provided.

Quantitative Evaluation Of Frequency Domain Measurements In High Density Diffuse Optical Tomography, Guy A. Perkins, Adam T. Eggebrecht, Hamid Dehghani

Open Access Publications

No abstract provided.

Bromodomain Protein Brd4 Directs And Sustains Cd8 T Cell Differentiation During Infection, J. Justin Milner, Takeshi Egawa, Et Al

Open Access Publications

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule-mediated BET inhibition impaired maintenance of a terminal …

Data Quality Methods Through Remote Source Data Verification Auditing: Results From The Congenital Cardiac Research Collaborative, Joelle A Pettus, Amy L Pajk, Andrew C Glatz, Christopher J Petit, Bryan H Goldstein, Athar M Qureshi, George T Nicholson, Jeffery J Meadows, Jeffrey D Zampi, Mark A Law, Shabana Shahanavaz, Michael S Kelleman, Courtney M Mccracken, Congenital Cardiac Research Collaborative

Open Access Publications

BACKGROUND: Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.

MATERIALS AND METHODS: The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into …

Survival Predictors Of Heart Rate Variability After Myocardial Infarction With And Without Low Left Ventricular Ejection Fraction, Junichiro Hayano, Norihiro Ueda, Masaya Kisohara, Emi Yuda, Robert M Carney, James A Blumenthal

Open Access Publications

Background: Heart rate variability (HRV) and heart rate (HR) dynamics are used to predict the survival probability of patients after acute myocardial infarction (AMI), but the association has been established in patients with mixed levels of left ventricular ejection fraction (LVEF).

Objective: We investigated whether the survival predictors of HRV and HR dynamics depend on LVEF after AMI.

Methods: We studied 687 post-AMI patients including 147 with LVEF ≤35% and 540 with LVEF >35%, of which 23 (16%) and 22 (4%) died during the 25 month follow-up period, respectively. None had an implanted cardioverter-defibrillator. From baseline 24 h ECG, the …

Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini

Open Access Publications

No abstract provided.

Perlecan In Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation And Mechanoregulation Of Load-Bearing Connective Tissues, Farshid Guilak, Anthony J Hayes, James Melrose

Open Access Publications

In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes …

Prognostic Assessment In High-Grade Soft-Tissue Sarcoma Patients: A Comparison Of Semantic Image Analysis And Radiomics, Jan C Peeken, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas of the extremities, the treatment decision is currently regularly based on tumor grading and size. The imaging-based analysis may pose an alternative way to stratify patients' risk. In this work, we compared the value of MRI-based radiomics with expert-derived semantic imaging features for the prediction of overall survival (OS).

METHODS: Fat-saturated T2-weighted sequences (T2FS) and contrast-enhanced T1-weighted fat-saturated (T1FSGd) sequences were collected from two independent retrospective cohorts (training: 108 patients; testing: 71 patients). After preprocessing, 105 radiomic features were extracted. Semantic imaging features were determined by three independent radiologists. Three machine learning techniques (elastic …

Aapm Medical Physics Practice Guideline 3.B.: Levels Of Supervision For Medical Physicists In Clinical Training, Douglas Pfeiffer, Hania Al-Hallaq, Per Halvorsen, Kristi Hendrickson, Zheng Feng Lu, Melissa Carol Martin, Beth Schueler, Jillian Shuman, Jacqueline E Zoberi

Open Access Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth …

Current And Prospective Methods For Assessing Anti-Tumor Immunity In Colorectal Cancer, Yulia I Nussbaum, Yariswamy Manjunath, Kanve N Suvilesh, Wesley C Warren, Chi-Ren Shyu, Jussuf T Kaifi, Matthew A Ciorba, Jonathan B Mitchem

Open Access Publications

Colorectal cancer (CRC) remains one of the deadliest malignancies worldwide despite recent progress in treatment strategies. Though immune checkpoint inhibition has proven effective for a number of other tumors, it offers benefits in only a small group of CRC patients with high microsatellite instability. In general, heterogenous cell groups in the tumor microenvironment are considered as the major barrier for unveiling the causes of low immune response. Therefore, deconvolution of cellular components in highly heterogeneous microenvironments is crucial for understanding the immune contexture of cancer. In this review, we assimilate current knowledge and recent studies examining anti-tumor immunity in CRC. …

Incidence And Burden Of Staphylococcus Aureus Infection After Orthopedic Surgeries, Jill G Dreyfus, Holly Yu, Elizabeth Begier, Julie Gayle, Margaret A Olsen

Open Access Publications

OBJECTIVE: To assess the 180-day incidence of Staphylococcus aureus infections following orthopedic surgeries using microbiology cultures.

DESIGN: Retrospective observational epidemiology study.

SETTING: National administrative hospital database.

PATIENTS: Adult patients with an elective admission undergoing orthopedic surgeries in the inpatient and hospital-based outpatient settings discharged between July 1, 2010, and June 30, 2015.

METHODS: Patients were identified from 181 hospitals reporting microbiology results to the Premier Healthcare Database. Orthopedic surgeries were defined using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure and current procedural terminology (CPT) codes. Microbiology cultures and ICD-9/10 diagnosis codes identified surgical site infections (SSIs), bloodstream …

Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge

Open Access Publications

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis

Approaches For Ending Ineffective Programs: Strategies From State Public Health Practitioners, Emily Rodriguez Weno, Peg Allen, Stephanie Mazzucca, Louise Farah Saliba, Margaret Padek, Sarah Moreland-Russell, Ross C Brownson

Open Access Publications

No abstract provided.

Identifying The Impact Of Intimate Partner Violence In Humanitarian Settings: Using An Ecological Framework To Review 15 Years Of Evidence, Melissa Meinhart, Ilana Seff, Katrina Troy, Samantha Mcnelly, Luissa Vahedi, Catherine Poulton, Lindsay Stark

Open Access Publications

Intimate partner violence (IPV) is a pervasive form of gender-based violence that exacerbates in humanitarian settings. This systematic review examined the myriad IPV impacts and the quality of existing evidence of IPV in humanitarian settings. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, a total of 51 articles were included from the 3924 screened. We identified the impact of IPV across two levels of the ecological framework: individual and microsystem. Our findings corroborated previous evidence that indicated IPV to be associated with adverse physical and mental health for survivors. Our findings also uniquely synthesized the intergenerational …

Pattern And Degree Of Individual Brain Atrophy Predicts Dementia Onset In Dominantly Inherited Alzheimer's Disease, Ophir Keret, Randal J Bateman, Tammie L S Benzinger, John C Morris, Beau M Ances, Nelly Joseph-Mathurin, Richard J Perrin, Brian A Gordon, Dominantly Inherited Alzheimer Network, Et Al

Open Access Publications

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.

Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.

Results: Our risk score separated asymptomatic versus demented …

Glembatumumab Vedotin For Patients With Metastatic, Gpnmb Overexpressing, Triple-Negative Breast Cancer (“Metric”): A Randomized Multicenter Study, Linda T. Vahdat, Cynthia Ma, Et Al.

Open Access Publications

No abstract provided.

Braf-Mek Inhibitors As Steroid-Sparing Bridge Prior To Checkpoint Blockade Therapy In Symptomatic Intracranial Melanoma, Karam Khaddour, Tanner M. Johanns, George Ansstas

Open Access Publications

The introduction of immune checkpoint blockade (ICB) and BRAF-MEK inhibitors has substantially improved outcomes in patients with metastatic melanoma. However, several challenging factors may hinder the efficacy of ICB in patients with symptomatic intracranial metastatic melanoma who are immunosuppressed due to the use of steroids prior to the administration of ICB. This has resulted in the exclusion of patients treated with high dose steroid at baseline from the majority of ICB clinical trials. In addition, despite the high efficacy of BRAF-MEK inhibitors in

Unsupervised Cluster Analysis Of Patients With Recovered Left Ventricular Ejection Fraction Identifies Unique Clinical Phenotypes, Andrew Perry, Francis Loh, Luigi Adamo, Kathleen W. Zhang, Elena Deych, Randi Foraker, Douglas L. Mann

Open Access Publications

BACKGROUND: Patients with heart failure (HF) with recovered ejection fraction (HFrecEF) are a recently identified cohort that are phenotypically and biologically different from HFrEF and HFpEF patients. Whether there are unique phenotypes among HFrecEF patients is not known.

METHODS: We studied all patients at a large medical center, who had an improvement in LVEF from ≤ 35% to ≥ 50% (LVrecEF) between January 1, 2005 and December 31, 2013. We identified a set of 11 clinical variables and then performed unsupervised clustering analyses to identify unique clinical phenotypes among patients with LVrecEF, followed by a Kaplan-Meier analysis to identify differences …

Mitochondria In Epithelial Ovarian Carcinoma Exhibit Abnormal Phenotypes And Blunted Associations With Biobehavioral Factors, Snehal Bindra, Marlon A. Mcgill, Marina K. Triplett, Anisha Tyagi, Premal H. Thaker, Laila Dahmoush, Michael J. Goodheart, R. Todd Ogden, Edward Owusu-Ansah, Kalpita R. Karan, Steve Cole, Anil K. Sood, Susan K. Lutgendorf, Martin Picard

Open Access Publications

No abstract provided.

Bispecific T Cell Engagers For The Treatment Of Multiple Myeloma: Achievements And Challenges, Kinan Alhallak, Jennifer Sun, Amanda Jeske, Chaelee Park, Jessica Yavner, Hannah Bash, Berit Lubben, Ola Adebayo, Ayah Khaskiah, Abdel Kareem Azab

Open Access Publications

MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.