Enhanced Place Specificity of the Parallel Auditory Brainstem Response: An Electrophysiological Study.

Purpose: This study investigates the effect of parallel stimulus presentation on the place specificity of the auditory brainstem response (ABR) in human listeners. Frequency-specific stimuli do not guarantee a response from the place on the cochlea corresponding only to that characteristic frequency - especially for brief and high-level stimuli. Adding masking noise yields responses that are more place specific, and our prior modeling study has suggested similar effects when multiple frequency-specific stimuli are presented in parallel.

Enhanced Place Specificity of the Parallel Auditory Brainstem Response: An Electrophysiological Study.

Purpose: This study investigates the effect of parallel stimulus presentation on the place specificity of the auditory brainstem response (ABR) in human listeners. Frequency-specific stimuli do not guarantee a response from the place on the cochlea corresponding only to that characteristic frequency - especially for brief and high-level stimuli. Adding masking noise yields responses that are more place specific, and a prior modeling study has suggested similar effects when multiple frequency-specific stimuli are presented in parallel.

Enhanced Place Specificity of the Parallel Auditory Brainstem Response: A Modeling Study.

While each place on the cochlea is most sensitive to a specific frequency, it will generally respond to a sufficiently high-level stimulus over a wide range of frequencies. This spread of excitation can introduce errors in clinical threshold estimation during a diagnostic auditory brainstem response (ABR) exam. Off-frequency cochlear excitation can be mitigated through the addition of masking noise to the test stimuli, but introducing a masker increases the already long test times of the typical ABR exam.

Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites.

Maturation rates of malaria parasites within red blood cells (RBCs) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongoing acute infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. Importantly, plasma from LPS-conditioned or acutely infected mice directly inhibited parasite maturation during in vitro culture, which was not rescued by supplementation, suggesting the emergence of inhibitory factors in plasma.

Segmental Acetabular Defects Managed by Augments in Conjunction with CT During Robotic Total Hip Arthroplasty: A Report of 2 Cases.

Cases: We present 2 robotic-assisted hip arthroplasty cases with significant segmental acetabular defects that could compromise cup fixation. We outline an algorithmic planning approach on a computed tomography (CT)-based platform to address these defects by predicting augmentation needs, when component adjustments alone are inadequate, and describe the novel combination of augments in conjunction with robotic-assisted hip arthroplasty.

Conclusion: CT-based robotic-assisted hip arthroplasty is a powerful tool to assess and address acetabular deficiencies.

Skin Cancer-Associated Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress.

Actinic keratosis (AK) is a premalignant lesion, common on severely photodamaged skin, that can progress over time to cutaneous squamous cell carcinoma (SCC). A high bacterial load of is associated with AK and SCC, but it is unknown whether this has a direct impact on skin cancer development. To determine whether can have cancer-promoting effects on skin cells, we performed RNA sequencing and shotgun proteomics on primary human keratinocytes after challenge with sterile culture supernatant ('secretome') from four clinical strains isolated from AK and SCC.

Elevation of fatty acid desaturase 2 in esophageal adenocarcinoma increases polyunsaturated lipids and may exacerbate bile acid-induced DNA damage.

Background: The risk of esophageal adenocarcinoma (EAC) is associated with gastro-esophageal reflux disease (GERD) and obesity. Lipid metabolism-targeted therapies decrease the risk of progressing from Barrett's esophagus (BE) to EAC, but the precise lipid metabolic changes and their roles in genotoxicity during EAC development are yet to be established.

Methods: Esophageal biopsies from the normal epithelium (NE), BE, and EAC, were analyzed using concurrent lipidomics and proteomics (n = 30) followed by orthogonal validation on independent samples using RNAseq transcriptomics (n = 22) and immunohistochemistry (IHC, n = 80).

Accelerometry-based physical activity, disability and quality of life before and after lumbar decompression surgery from a physiotherapeutic perspective: An observational cohort study.

Background: The effect of lumbar decompression on physical activity (PA) measures (measured as number of steps/day and as moderate to vigorous PA (MVPA)) is poorly understood. The aim of the current study was to compare PA in patients before and after lumbar decompression and to determine the association between change in steps/day and MVPA with change in disability, health-related quality of life (HRQOL) and pain.

Methods: Patients undergoing lumbar decompression surgery were recruited.

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

Objective: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases.

Ex vivo glucocorticoid-induced secreted proteome approach for discovery of glucocorticoid-responsive proteins in human serum.

Purpose: To identify glucocorticoid-responsive proteins measurable in human serum that may have clinical utility in therapeutic drug monitoring and the diagnosis of cortisol excess or deficiency.

Experimental Design: A phased biomarker discovery strategy was conducted in two cohorts. Secretome from peripheral blood mononuclear cells (PBMC) isolated from six volunteers after ex vivo incubation ± dexamethasone (DEX) 100 ng/mL for 4 h and 24 h was used for candidate discovery and qualification using untargeted proteomics and a custom multiple reaction monitoring mass spectrometry (MRM-MS) assay, respectively.

Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.

Objectives: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000.

Accrual of Atherosclerotic Vascular Events in a Multicenter Inception Systemic Lupus Erythematosus Cohort.

Objective: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE.

Methods: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017.

Antibody-Free Multiplex Measurement of 23 Human Cytokines in Primary Cell Culture Secretome Using Targeted Mass Spectrometry.

Cytokines are commonly measured by immunoassays; however, these have limited multiplexing capacity, are costly, and can exhibit cross-reactivity. Multiple reaction monitoring (MRM) mass spectrometry is a robust method to quantify analytes with high specificity and multiplexing ability, hence we aimed to investigate its suitability as an alternative cost-effective method for cytokine measurement. Human keratinocyte conditioned media spiked with recombinant cytokines was used as an experimental system to evaluate sensitivity, linearity, and reproducibility of an MRM assay targeting 79 peptides representing 23 human cytokines.

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression.

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus.

Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach.

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling.

Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis.

Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis.

Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (Ov) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer.

Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis.

Cholangiocarcinoma (CCA) is a major health problem in northeastern Thailand. The majority of CCA cases are clinically silent and difficult to detect at an early stage. Although abdominal ultrasonography (US) can detect premalignant periductal fibrosis (PDF), this method is not suitable for screening populations in remote areas.

Integration of Two In-depth Quantitative Proteomics Approaches Determines the Kallikrein-related Peptidase 7 (KLK7) Degradome in Ovarian Cancer Cell Secretome.

Kallikrein-related peptidase 7 (KLK7) is a serine peptidase that is over expressed in ovarian cancer. functional analyses have suggested KLK7 to play a cancer progressive role, although monitoring of KLK7 expression has suggested a contradictory protective role for KLK7 in ovarian cancer patients. In order to help delineate its mechanism of action and thereby the functional roles, information on its substrate repertoire is crucial.

Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort.

Objective: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.

Methods: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available.

Development of a Rapid BioID System as a Probe for Plasma Membrane-Associated Immunity Proteins.

Plant pathogens secrete effector molecules that suppress the plant immune response to facilitate disease development. AvrPto is a well-studied effector from the phytopathogenic bacterium . Here we utilize an proximity dependent biotin ligase labeling technique (BioID) in combination with AvrPto to identify proximal proteins that are potential immune system components.

Proteomics of the wheat tan spot pathogen Pyrenophora tritici-repentis.

Objectives: The fungus Pyrenophora tritici-repentis is a major pathogen of wheat worldwide, causing the leaf spotting disease tan spot. To best inform approaches for plant genetic resistance, an understanding of the biology and pathogenicity mechanisms of this fungal pathogen is essential. Here, intracellular and extracellular proteins of P.