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Author: David Elashoff (283)


Apr
2018

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of contains ligands, such as tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria.

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Mar
2018

Multiparametric MRI (mpMRI) and biopsy-based molecular tests such as the 17-gene Oncotype DX Genomic Prostate Score™ (GPS) assay are increasingly used to improve risk stratification in men with clinically localized prostate cancer (PCa). The GPS assay was previously shown to be a significant independent predictor of adverse pathology (AP) at radical prostatectomy (RP) in men diagnosed with systematic biopsies only. We therefore investigated the ability of GPS to predict AP in the setting of MRI-guided prostate biopsy.

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Jan
2018

In severe circulatory failure agreement between arterial and mixed venous or central venous values is poor; venous values are more reflective of tissue acid-base imbalance. No prior study has examined the relationship between peripheral venous blood gas (VBG) values and arterial blood gas (ABG) values in hemodynamic compromise. The objective of this study was to examine the correlation between hemodynamic parameters, specifically systolic blood pressure (SBP) and the arterial-peripheral venous (A-PV) difference for all commonly used acid-base parameters (pH, Pco, and bicarbonate).

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Feb
2018

Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses.

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Jan
2018

We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related.

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Mar
2018

Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown.

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Dec
1969

Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers.

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Dec
1969

Classification models can demonstrate apparent prediction accuracy even when there is no underlying relationship between the predictors and the response. Variable selection procedures can lead to false positive variable selections and overestimation of true model performance. A simulation study was conducted using logistic regression with forward stepwise, best subsets, and LASSO variable selection methods with varying total sample sizes (20, 50, 100, 200) and numbers of random noise predictor variables (3, 5, 10, 15, 20, 50).

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Dec
2017

Obesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers.

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Feb
2018

To evaluate the impact of cone beam CT (CBCT) in the diagnostic thinking efficacy, management and prognosis of patients with suspected Stage 0 medication-related osteonecrosis of the jaw (MRONJ).
For 15 patients with suspected Stage 0 MRONJ, clinical photographs, a panoramic radiograph and selected CBCT sections were identified. 13 oral surgeons reviewed the material and answered 10 questions in two different sessions.

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Nov
2017

Surgical patients aged 65 and over face a higher risk of cardiac complications from noncardiac surgery. The Revised Cardiac Risk Index (RCRI) and the Gupta Myocardial Infarction or Cardiac Arrest (MICA) calculator are widely used to predict this risk, but they are not specifically designed to predict MICA in geriatric patients. Our hypothesis is that a new geriatric-sensitive index, derived from geriatric data, will capture this population's unique response to risk factors.

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Dec
2017

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated.
The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014.

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Jan
2017

Alzheimer's disease (AD) incidence is disproportionately high in African Americans, yet, recruitment of this community to AD clinical trials is challenging.
We compared 47 African Americans and 78 whites in their willingness to enroll in a hypothetical preclinical AD trial and examined barriers and facilitators in their decision making.
African American race (OR = 0.

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Oct
2017

Research has revealed that manifest Alzheimer's disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms.

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Dec
1969

Analysis of RNA sequencing (RNA-Seq) data in human saliva is challenging. Lack of standardization and unification of the bioinformatic procedures undermines saliva's diagnostic potential. Thus, it motivated us to perform this study.

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Jan
2018

Angiotensin II type 1 receptor (AT1R) antibody has been linked to poor allograft outcomes in adult kidney transplantation. However, its clinical consequences in children are unknown. To study this, we examined the relationship of AT1R antibody with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibodies (DSA) in a cohort of pediatric renal transplant recipients.

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Jan
2018

Objective To evaluate the adverse effects and therapeutic efficacy of our biocompatible polymer platform delivering targeted local therapy of cytokine CCL21 and cisplatin in a partially resected xenograft animal model of head and neck squamous cell carcinoma. In addition, to evaluate the efficacy of cotreatment with radiotherapy and assess the biocompatibility of the cisplatin-eluting polymer in the murine neck. Study Design Experimental animal study.

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Nov
2017

We have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data were also available.

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Oct
2017

Insulin resistance (IR) detection is challenging and no test is currently used in clinical practice. We developed salivary biomarkers that could be used for IR detection.
We collected saliva from 186 healthy and 276 pre-diabetic participants, divided them into high and low IR groups based on a HOMA cutoff of 2.

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Jul
2017

Poor sleep and immobility are common in patients in the medical intensive care unit (MICU) and are associated with adverse outcomes. Interventions to promote sleep and mobilization in the MICU are gaining popularity, but feasible instruments to measure their effectiveness are lacking. Actigraphy may be useful for large-scale, continuous measurement of sleep and activity, but its feasibility in MICU patients has not been rigorously evaluated.

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Aug
2017

Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.

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Dec
1969

All published studies of health care utilization in gout have been cross-sectional to date, and most used a patient-reported diagnosis of gout. Our objective was to assess health care utilization and its predictors in patients with physician-confirmed gout in a prospective cohort study.
In a multi-center prospective cohort study of U.

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Mar
2017

The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles.

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Aug
2017

A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following vaccination (ClinicalTrials.gov: NCT01574222).

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Dec
1969

Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we initially undertook microarrays targeting microRNAs in a small sub-set of placentas of appropriate (AGA) versus small for gestational age (SGA) weight infants, and observed up-regulation of 97 miRs and down-regulation of 44 miRs in SGA versus AGA.

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Oct
2017

To compare diagnostic test ordering practices of NPs with those of physicians in the role of Provider in Triage (PIT).
This was a secondary analysis of data from a prospective RCT of waiting room diagnostic testing, where 770 patients had diagnostic studies ordered from the waiting room. The primary outcome was the number of test categories ordered by provider type.

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Dec
1969

There are limited data on factors associated with retention in Option B+. We sought to explore the characteristics of women retained in Option B+ in Malawi, with a focus on the role of HIV disclosure, awareness of partner HIV status, and knowledge around the importance of Option B+ for maternal-child health. We performed a case-control study of HIV-infected women in Malawi initiated on antiretroviral therapy (ART) under Option B+.

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May
2017

We explored the association between liver metastases, tumor CD8 T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.

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Dec
1969

High-density lipoprotein (HDL) function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic treated HIV-1 infection.

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Dec
1969

Both theoretical and statistically derived approaches have been used in research settings for predicting cognitive decline.
Fifty-eight cognitively normal (NC) and 71 mild cognitive impairment (MCI) subjects completed a comprehensive cognitive battery for up to 5 years of follow-up. Composite indices of cognitive function were derived using a classic theoretical approach and exploratory factor analysis (EFA).

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Dec
1969

Clinical swollen joint examination of the obese rheumatoid arthritis (RA) patient can be difficult. Musculoskeletal Ultrasound (MSUS) has higher sensitivity than physical examination for swollen joints (SJ). The purpose of this study was to determine the joint-specific association between power Doppler (PDUS) and clinical SJ in RA across body mass index (BMI) categories.

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Aug
2017

Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.
Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

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Sep
2016

Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal-luminal interface to study the disease-related biology of the human colonic mucosa.
We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects.

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Dec
1969

Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.
In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients.

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Dec
1969

We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism.
We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8.

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Jan
2017

To compare the health-related quality of life (HRQOL) and the functional ability by race in patients with gout.
In a 9-month prospective cohort multicentre study, patients with gout self-reported race, dichotomized as Caucasian or African American (others excluded). We calculated HRQOL/function scores adjusted for age, study site and college education for Short Form-36 (SF-36; generic HRQOL), Gout Impact Scale (GIS; disease-specific HRQOL) and HAQ-disability index (HAQ-DI; functional ability).

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Jan
2017

Intensity-modulated radiotherapy (IMRT) is a dose-delivery technology allowing for a reduction in radiotherapy side effects. It has been rapidly adopted despite the lack of prospective studies showing improved outcomes. We sought to compare the cost through Medicare reimbursement patterns of surgery, IMRT, and conventional XRT in treating head and neck cancer.

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Dec
1969

Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38 luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling.

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Dec
1969

Echocardiography-based speckle-tracking strain imaging is an emerging modality to assess left ventricular function. The aim of this study was to investigate the change in left ventricular systolic function after cardiac surgery with 3-dimensional (3D) speckle-tracking strain imaging and to determine whether preoperative 3D strain is an independent predictor of acute and long-term clinical outcomes after aortic valve, mitral valve, and coronary artery bypass grafting operations.
In total, 163 adult patients undergoing aortic valve, mitral valve, and coronary artery bypass surgeries were enrolled prospectively and had complete data sets.

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Nov
2016

The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized HDL and LDL (HDLox and LDLox) contribute to HIV-1-related immune dysfunction.
In the AIDS Clinical Trials Group A5260, 234 HIV-infected antiretroviral therapy (ART)-naive participants were randomized to receive tenofovir-emtricitabine and protease inhibitors or raltegravir and had HIV-1 RNA less than 50 copies/ml by week 24 and thereafter.

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Jan
2017

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center.

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Dec
1969

OBJECTIVE To evaluate the impact of discontinuation of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) and expansion of chlorhexidine gluconate (CHG) use on the health system. DESIGN Retrospective, nonrandomized, observational, quasi-experimental study. SETTING Two California hospitals.

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Dec
1969

Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation.

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Dec
1969

In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC).
Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.
p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail.

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Mar
2017

The effect of clinician screening of patients in the emergency department (ED) waiting room is unclear. This study aims to determine the effect of initiating laboratory and imaging studies from the ED waiting room on time in a bed, total ED time, and likelihood of patients leaving before completion of service.
This was a prospective, randomized, controlled trial evaluating 1,659 nonpregnant adults with a chief complaint of abdominal pain, conducted in a public hospital ED when all ED beds were occupied and patients were in the waiting room awaiting definitive evaluation.

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Dec
1969

Abnormal function of high-density lipoprotein (HDL) has been implicated as a potential mechanism for the increased incidence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). This study was undertaken to evaluate changes in HDL function and HDL-associated proteins over 2 years of follow-up in patients with early RA receiving either methotrexate (MTX) monotherapy, MTX + etanercept (ETN) combination therapy, or MTX + sulfasalazine (SSZ) + hydroxychloroquine (HCQ) triple therapy in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.
The antioxidant capacity of HDL, paraoxonase 1 (PON-1) activity, and levels of HDL-associated haptoglobin (Hp), HDL-associated apolipoprotein A-I (Apo A-I), and myeloperoxidase (MPO) were measured in 550 TEAR participants at 4 time points (time 0 [pretreatment] and at 24, 48, and 102 weeks of treatment).

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Jun
2016

Background : Hepatitis C (HCV) direct acting antiviral agents (DAAs) are safe, effective, and tolerable. Most contraindications to interferon-based treatment are no long applicable. The aims of this study were to understand the predictors of approval to drug accessibility.

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