Digital Commons Network^™

Metformin Downregulates Pd-L1 Expression In Esophageal Squamous Cell Catrcinoma By Inhibiting Il-6 Signaling Pathway, Yao Lu, Dao Xin, Lulu Guan, Mengli Xu, Yalan Yang, Yu Chen, Yuanyuan Yang, Andrea Wang-Gillam, Li Wang, Shanggang Zong, Feng Wang

Open Access Publications

Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.

Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin …

Metavariables Resuming Host Immune Features And Nodal Involvement Are Associated With Oncological Outcomes In Oral Cavity Squamous Cell Carcinoma, Francesco Missale, Mattia Bugatti, Davide Mattavelli, Silvia Lonardi, Davide Lombardi, Piero Nicolai, Cesare Piazza, Simonetta Battocchio, Anna Maria Bozzola, Stefano Calza, William Vermi

Open Access Publications

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8

Quantification Of Sepsis Model Alerts In 24 Us Hospitals Before And During The Covid-19 Pandemic, Andrew Wong, Jie Cao, Patrick G. Lyons, Sayon Dutta, Vincent J. Major, Erkin Ötles, Karandeep Singh

Open Access Publications

No abstract provided.

A Unique Cardiovascular Presentation Of Pheochromocytoma, William Orr, Riti Chokshi, Georgeann Groh, Jennifer N. Avari Silva, George Van Hare, Aarti Dalal

Open Access Publications

We describe a unique presentation of a pheochromocytoma in a normotensive teenager, who presented with symptoms of headache, neck pain, and palpitations. Holter and event monitor tracings revealed intermittent junctional rhythm causing electromechanical dyssynchrony between atrial and ventricular contraction resulting in reported symptoms. Exercise stress testing helped correlate symptomatic junctional rhythm events to episodic hypertension which led to the eventual diagnosis of pheochromocytoma. The exercise test provided insight into the physiologic coupling that the sympathetic and parasympathetic autonomic nervous systems have on the cardiovascular system during exercise and exaggerated hypertension. The patient was found to have MEN2A and partial adrenalectomy …

Predicting Mortality Among Patients With Liver Cirrhosis In Electronic Health Records With Machine Learning, Aixia Guo, Nikhilesh R. Mazumder, Daniela P. Ladner, Randi E. Foraker

Open Access Publications

OBJECTIVE: Liver cirrhosis is a leading cause of death and effects millions of people in the United States. Early mortality prediction among patients with cirrhosis might give healthcare providers more opportunity to effectively treat the condition. We hypothesized that laboratory test results and other related diagnoses would be associated with mortality in this population. Our another assumption was that a deep learning model could outperform the current Model for End Stage Liver disease (MELD) score in predicting mortality.

MATERIALS AND METHODS: We utilized electronic health record data from 34,575 patients with a diagnosis of cirrhosis from a large medical center …

Pharmacokinetics Of Single Domain Antibodies And Conjugated Nanoparticles Using A Hybrid Near Infrared Method, Shiran Su, Thomas J Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H Kim, David L Brody

Open Access Publications

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain …

Emerging Nanotechnology For Treatment Of Alzheimer's And Parkinson's Disease, Amanda Li, Joel Tyson, Shivni Patel, Meer Patel, Sruthi Katakam, Xiaobo Mao, Weiwei He

Open Access Publications

The prevalence of the two most common neurodegenerative diseases, Parkinson's disease (PD) and Alzheimer's Disease (AD), are expected to rise alongside the progressive aging of society. Both PD and AD are classified as proteinopathies with misfolded proteins α-synuclein, amyloid-β, and tau. Emerging evidence suggests that these misfolded aggregates are prion-like proteins that induce pathological cell-to-cell spreading, which is a major driver in pathogenesis. Additional factors that can further affect pathology spreading include oxidative stress, mitochondrial damage, inflammation, and cell death. Nanomaterials present advantages over traditional chemical or biological therapeutic approaches at targeting these specific mechanisms. They can have intrinsic properties …

Familial History Of Autoimmune Disorders Among Patients With Pediatric Multiple Sclerosis, Benjamin M. Greenberg, Soe S. Mar, Shannon Liang, Manu Goyal, Et Al

Open Access Publications

No abstract provided.

Initial Experience With Single-Port Robot-Assisted Radical Cystectomy: Comparison Of Perioperative Outcomes Between Single-Port And Conventional Multiport Approaches, James T. Gross, Joel M. Vetter, Kenneth G. Sands, Joshua K. Palka, Sam B. Bhayani, Robert S. Figenshau, Eric H. Kim

Open Access Publications

No abstract provided.

The Impact Of Psychological Factors And Their Treatment On The Results Of Total Knee Arthroplasty, Gregory S Kazarian, Christopher A Anthony, Charles M Lawrie, Robert L Barrack

Open Access Publications

➤: There is a growing body of evidence implicating psychosocial factors, including anxiety, depression, kinesiophobia, central sensitization, and pain catastrophizing, as negative prognostic factors following total knee arthroplasty (TKA).

➤: Symptoms of anxiety and depression likely represent risk factors for negative outcomes in patients undergoing TKA. However, few studies have assessed the impact of preoperative interventions for these conditions on postoperative outcomes.

➤: The Tampa Scale of Kinesiophobia and the Central Sensitization Inventory have demonstrated value in the diagnosis of kinesiophobia and central sensitization. Higher preoperative indices of kinesiophobia and central sensitization predict worse patient-reported outcomes postoperatively.

➤: Although evidence …

Work Organization Factors Associated With Health And Work Outcomes Among Apprentice Construction Workers: Comparison Between The Residential And Commercial Sectors, Ann Marie Dale, Diane S Rohlman, Lisa Hayibor, Bradley A Evanoff

Open Access Publications

There are substantial differences in work organization between residential and commercial construction sectors. This paper examined differences in work factors between construction sectors and examined the association between sector and health behaviors, health outcomes, and work outcomes. We surveyed 929 male construction apprentices (44% residential and 56% commercial) and found that residential apprentices reported fewer workplace safety policies, higher frequency of heavy lifting, and greater likelihood of reporting musculoskeletal pain compared to apprentices in commercial work. Residential apprentices reported higher job strain, lower supervisor support, more lost workdays due to pain or injury, and lower productivity related to health than …

Glucose-Mediated De Novo Lipogenesis In Photoreceptors Drives Early Diabetic Retinopathy, Rithwick Rajagopal, Beau Sylvester, Sheng Zhang, Sangeeta Adak, Xiaochao Wei, Megan Bowers, Sebastian Jessberger, Fong-Fu Hsu, Clay F. Semenkovich

Open Access Publications

No abstract provided.

Achieving A Diverse, Equitable, And Inclusive Environment For The Black Orthopaedic Surgeon: Part 1: Barriers To Successful Recruitment Of Black Applicants, Gabriella E Ode, Letitia Bradford, William A Ross, Eric W Carson, Jaysson T Brooks

Open Access Publications

No abstract provided.

Sex Differences In Clinical Outcomes Following Surgical Treatment Of Femoroacetabular Impingement, Tristan Maerz, Jeffrey J Nepple, Asheesh Bedi, Ira Zaltz, Étienne Belzile, Paul E Beaulé, Ernest L Sink, John C Clohisy, Anchor Group

Open Access Publications

BACKGROUND: Sex-based differences in clinical outcomes following surgical treatment of femoroacetabular impingement remain largely uncharacterized; this prospective, multicenter study evaluated these differences both directly and adjusted for covariates.

METHODS: Hips undergoing surgical treatment of symptomatic femoroacetabular impingement were prospectively enrolled in a multicenter cohort. Patient demographics, radiographic parameters, intraoperatively assessed disease severity, and history of surgical procedures, as well as patient-reported outcome measures, were collected preoperatively and at a mean follow-up of 4.3 years. A total of 621 (81.6%) of 761 enrolled hips met the minimum 1 year of follow-up and were included in the analysis; 56.7% of analyzed hips …

Barriers And Facilitators To Qualitative Data Sharing In The United States: A Survey Of Qualitative Researchers, Jessica Mozersky, Tristan Mcintosh, Heidi A. Walsh, Meredith V. Parsons, Melody Goodman, James M. Dubois

Open Access Publications

Qualitative health data are rarely shared in the United States (U.S.). This is unfortunate because gathering qualitative data is labor and time-intensive, and data sharing enables secondary research, training, and transparency. A new U.S. federal policy mandates data sharing by 2023, and is agnostic to data type. We surveyed U.S. qualitative researchers (N = 425) on the barriers and facilitators of sharing qualitative health or sensitive research data. Most researchers (96%) have never shared qualitative data in a repository. Primary concerns were lack of participant permission to share data, data sensitivity, and breaching trust. Researcher willingness to share would increase …

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 …

The Risks Of Stone Diagnosis And Stone Removal Procedure After Different Bariatric Surgeries, Steven M. Monda, Joel M. Vetter, Margaret A. Olsen, Matthew R. Keller, J. Christopher Eagon, Michael S. Chevinsky, Vasian Markollari, Ramakrishna Venkatesh, Alana C. Desai

Open Access Publications

No abstract provided.

Differences In Effectiveness And Use Of Laparoscopic Surgery In Locally Advanced Colon Cancer Patients, M. Schootman, Matthew Mutch, T. Loux, J.M. Eberth, N.O. Davidson

Open Access Publications

No abstract provided.

Local Field Potentials In The Parietal Reach Region Reveal Mechanisms Of Bimanual Coordination, Eric Mooshagian, Charles D. Holmes, Lawrence H. Snyder

Open Access Publications

No abstract provided.

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 …

Application Programming Interface Guided Qa Plan Generation And Analysis Automation, Matthew C Schmidt, Caleb A Raman, Yu Wu, Mahmoud M Yaqoub, Yao Hao, Rebecca Nichole Mahon, Matthew J Riblett, Nels C Knutson, Erno Sajo, Piotr Zygmanski, Marian Jandel, Francisco J Reynoso, Baozhou Sun

Open Access Publications

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process.

METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing …

High Optode-Density Wearable Diffuse Optical Probe For Monitoring Paced Breathing Hemodynamics In Breast Tissue, Samuel S. Spink, Fei Teng, Vivian Pera, Hannah M. Peterson, Tim Cormier, Alexis Sauer-Budge, David Chargin, Sam Brookfield, Adam T. Eggebrecht, Naomi Ko, Darren Roblyer

Open Access Publications

No abstract provided.

Innovations In Md-Only Physician-Scientist Training: Experiences From The Burroughs Wellcome Fund Physician-Scientist Institutional Award Initiative, Allison T Mcelvaine, Jacqueline A Hawkins-Salsbury, Wayne M Yokoyama, Et Al

Open Access Publications

No abstract provided.

Unexpected Role Of Sterol Synthesis In Rna Stability And Translation In Leishmania, Zemfira N Karamysheva, Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B Tikhonova, Andrey L Karamyshev, Kai Zhang

Open Access Publications

No abstract provided.

Development And External Validation Of Deep-Learning-Based Tumor Grading Models In Soft-Tissue Sarcoma Patients Using Mr Imaging, Fernando Navarro, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas, tumor grading constitutes a decisive factor to determine the best treatment decision. Tumor grading is obtained by pathological work-up after focal biopsies. Deep learning (DL)-based imaging analysis may pose an alternative way to characterize STS tissue. In this work, we sought to non-invasively differentiate tumor grading into low-grade (G1) and high-grade (G2/G3) STS using DL techniques based on MR-imaging.

METHODS: Contrast-enhanced T1-weighted fat-saturated (T1FSGd) MRI sequences and fat-saturated T2-weighted (T2FS) sequences were collected from two independent retrospective cohorts (training: 148 patients, testing: 158 patients). Tumor grading was determined following the French Federation of Cancer …

Combined Effect Of Lead Exposure And Allostatic Load On Cardiovascular Disease Mortality-A Preliminary Study, Emmanuel Obeng-Gyasi, Alesia C Ferguson, Katherine A Stamatakis, Michael A Province

Open Access Publications

This study explores the combined effect of lead (Pb) exposure and an index of chronic physiological stress on cardiovascular disease mortality using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2008 linked to 1999-2014 National Death Index data. Chronic physiological stress was measured using the allostatic load (AL) index, which was formed by analyzing markers from the cardiovascular, inflammatory, and metabolic systems, with Pb levels, assessed using blood lead levels (BLL). The dataset was analyzed with statistical techniques to explore (a) the relationship between Pb exposure and AL, and (b) the combined role of Pb and AL on …

Engaging Caregivers And Providers Of Children With Sickle Cell Anemia In Shared Decision Making For Hydroxyurea: Protocol For A Multicenter Randomized Controlled Trial, Anna M Hood, Allison A King, Cecelia Calhoun, Et Al

Open Access Publications

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term …

A Microfluidic-Based Filtration System To Enrich For Bone Marrow Disseminated Tumor Cells From Breast Cancer Patients, Sreeraj G. Pillai, Chidananda M. Siddappa, Cynthia Ma, Jackie Snider, Madhurima Kaushal, Mark A. Watson, Rebecca Aft

Open Access Publications

Disseminated tumors cells (DTCs) present in the bone marrow (BM) are believed to be the progenitors of distant metastatic spread, a major cause of mortality in breast cancer patients. To better understand the behavior and therapeutic vulnerabilities of these rare cell populations, unbiased methods for selective cell enrichment are required. In this study, we have evaluated a microfluidic-based filtration system (ParsortixR, Angle PLC), previously demonstrated for use in circulating tumor cell (CTC) capture, to capture BM DTCs. Performance using BM samples was also compared directly to enrichment of CTCs in the peripheral blood (PB) from both metastatic and non-metastatic breast …

Targeting The Gut To Treat Multiple Sclerosis, Laura Ghezzi, Claudia Cantoni, Gabriela V Pinget, Yanjiao Zhou, Laura Piccio

Open Access Publications

The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies …

Cisplatin Ototoxicity: Examination Of The Impact Of Dosing, Infusion Times, And Schedules In Pediatric Cancer Patients, Miranda L Camet, Anne Spence, Susan S Hayashi, Ningying Wu, Jennifer Henry, Kara Sauerburger, Robert J Hayashi

Open Access Publications

Background: Sensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss.

Methods: A retrospective review of 993 pediatric patients' medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical …