Identifying meaningful aspects of health and concepts of interest for assessment in systemic lupus erythematosus: implications for digital clinical measure development.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical manifestations which significantly impacts the daily lives of patients. Herein, we aimed to (i) investigate patients' perspectives on and experience with SLE; (ii) identify meaningful aspects of health (MAHs) and concepts of interest (COIs) in SLE that could be evaluated using digital clinical measures (DCMs); and (iii) identify target DCMs for their assessment.

Methods: A mixed-methods, multistep approach was deployed for (i) exploring patients' experience with SLE through a social media listening study and focused group discussions with patients; (ii) mapping patients' experiences to define MAHs and identify COIs measurable using DCMs; (iii) selecting DCMs for the target COIs; and (iv) identifying types of wearable sensors for measuring COIs in the patients.

Developing molecular classifiers to detect environmental stressors, smolt stages and morbidity in coho salmon, Oncorhynchus kisutch.

Aquatic species are increasingly confronted with environmental stressors because of climate change. Although molecular technologies have advanced our understanding of how organisms respond to stressors in laboratory settings, the ability to detect physiological responses to specific stressors under complex field conditions remains underdeveloped. This research applied multi-stressor challenge trials on coho salmon, employing the "Salmon Fit-Chips" genomic tool and a random forest-based classification model to develop classifiers predictive for chronic thermal and hypoxic stress, as well as salinity acclimation, smolt stage and morbidity status.

Comprehensive immune profiling of SARS-CoV-2 infected kidney transplant patients.

Introduction: The immune responses of kidney transplant recipients against SARS-CoV-2 remains under studied.

Methods: In this prospective pilot study, we performed comprehensive immune profiling using cellular, proteomic, and serologic assays on a cohort of 9 kidney transplant recipients and 12 non-transplant individuals diagnosed with COVID-19.

Results: Our data show that in addition to having reduced SARS-CoV-2 specific antibody levels, kidney transplant recipients exhibited significant cellular differences including a decrease in naïve-but increase in effector T cells, a high number of CD28+ CD4 effector memory T cells, and increased CD8 T memory stem cells compared with non-transplant patients.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

Background: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures.

Disease course following High Disease Activity Status revealed patterns in SLE.

Background: We sought to examine the disease course of High Disease Activity Status (HDAS) patients and their different disease patterns in a real-world longitudinal cohort. Disease resolution till Lupus Low Disease Activity State (LLDAS) has been a general treatment goal, but there is limited information on this subset of patients who achieve this.

Methods: All consenting patients of the Monash Lupus Cohort who had at least 12 months of observation were included.

High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation.

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms.

Discovery and surveillance of viruses from salmon in British Columbia using viral immune-response biomarkers, metatranscriptomics, and high-throughput RT-PCR.

The emergence of infectious agents poses a continual economic and environmental challenge to aquaculture production, yet the diversity, abundance, and epidemiology of aquatic viruses are poorly characterised. In this study, we applied salmon host transcriptional biomarkers to identify and select fish in a viral disease state, but only those that were negative for known viruses based on RT-PCR screening. These fish were selected for metatranscriptomic sequencing to discover potential viral pathogens of dead and dying farmed Atlantic () and Chinook () salmon in British Columbia (BC).

Algorithm for calculating high disease activity in SLE.

Background: The ability to identify lupus patients in high disease activity status (HDAS) without knowledge of the SLEDAI could have application in selection of patients for treatment escalation or enrolment in trials. We sought to generate an algorithm that could calculate via model fitting the presence of HDAS using simple demographic and laboratory values.

Methods: We examined the association of high disease activity (HDA) with demographic and laboratory parameters using prospectively collected data.

Testosterone therapy: Prescribing and monitoring patterns of practice in British Columbia.

Introduction: Guidelines recommend that testosterone therapy (TTh) be restricted to men with a biochemical diagnosis of hypogonadism, and that therapeutic responses be titrated within the normal range.

Methods: Using four provincial longitudinal databases in British Columbia, we identified men prescribed TTh from 1997-2013. We characterized the prescribing and monitoring practices of TTh in the context of serum testosterone levels drawn prior to and following initiation of TTh in a population-based setting.

Identification of Hypoxia-Specific Biomarkers in Salmonids Using RNA-Sequencing and Validation Using High-Throughput qPCR.

Identifying early gene expression responses to hypoxia (, low dissolved oxygen) as a tool to assess the degree of exposure to this stressor is crucial for salmonids, because they are increasingly exposed to hypoxic stress due to anthropogenic habitat change, , global warming, excessive nutrient loading, and persistent algal blooms. Our goal was to discover and validate gill gene expression biomarkers specific to the hypoxia response in salmonids across multi-stressor conditions. Gill tissue was collected from 24 freshwater juvenile Chinook salmon (), held in normoxia [dissolved oxygen (DO) > 8 mg L] and hypoxia (DO = 4‒5 mg L) in 10 and 18° temperatures for up to six days.

Discovery and validation of candidate smoltification gene expression biomarkers across multiple species and ecotypes of Pacific salmonids.

Early marine survival of juvenile salmon is intimately associated with their physiological condition during smoltification and ocean entry. Smoltification (parr-smolt transformation) is a developmental process that allows salmon to acquire seawater tolerance in preparation for marine living. Traditionally, this developmental process has been monitored using gill Na/K-ATPase (NKA) activity or plasma hormones, but gill gene expression offers the possibility of another method.

Salmonid gene expression biomarkers indicative of physiological responses to changes in salinity and temperature, but not dissolved oxygen.

An organism's ability to respond effectively to environmental change is critical to its survival. Yet, life stage and overall condition can dictate tolerance thresholds to heightened environmental stressors, such that stress may not be equally felt across individuals and at all times. Also, the transcriptional responses induced by environmental changes can reflect both generalized responses as well as others that are highly specific to the type of change being experienced.

Developing specific molecular biomarkers for thermal stress in salmonids.

Background: Pacific salmon (Oncorhynchus spp.) serve as good biological indicators of the breadth of climate warming effects on fish because their anadromous life cycle exposes them to environmental challenges in both marine and freshwater environments. Our study sought to mine the extensive functional genomic studies in fishes to identify robust thermally-responsive biomarkers that could monitor molecular physiological signatures of chronic thermal stress in fish using non-lethal sampling of gill tissue.

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis.

Molecular indices of viral disease development in wild migrating salmon.

Infectious diseases can impact the physiological performance of individuals, including their mobility, visual acuity, behavior and tolerance and ability to effectively respond to additional stressors. These physiological effects can influence competitiveness, social hierarchy, habitat usage, migratory behavior and risk to predation, and in some circumstances, viability of populations. While there are multiple means of detecting infectious agents (microscopy, culture, molecular assays), the detection of infectious diseases in wild populations in circumstances where mortality is not observable can be difficult.

Pathologic fracture and healthcare resource utilisation: A retrospective study in eight European countries.

Background: Skeletal-related events (SREs; pathologic fracture [PF], spinal cord compression and radiation or surgery to bone) are common complications of bone metastases or bone lesions and can impose a considerable burden on patients and healthcare systems. In this study, the healthcare resource utilisation (HRU) associated with PFs in patients with bone metastases or lesions secondary to solid tumours or multiple myeloma was estimated in eight European countries.

Methods: Eligible patients were identified in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland.

Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers.

Background: Air pollution's association with asthma may be due to its augmentation of allergenic effects, but the role of microRNA (miRNA) and gene expression in this synergy is unknown.

Objective: We sought to determine whether exposure to allergen, exposure to diesel exhaust (DE), or coexposures modulate miRNA, gene expression, or inflammatory pathways and whether these measurements are correlated.

Methods: Fifteen participants with atopy completed this controlled study of 2 hours of filtered air or DE (300 μg PM/m) exposure, followed by saline-controlled segmental bronchial allergen challenge.

Health resource utilization associated with skeletal-related events: results from a retrospective European study.

Background: Bone complications, also known as skeletal-related events (SREs), are common in patients with bone metastases secondary to advanced cancers.

Objective: To provide a detailed estimate of the health resource utilization (HRU) burden associated with SREs across eight European countries.

Methods: Eligible patients from centers in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden, and Switzerland with bone metastases or lesions secondary to breast cancer, prostate, or lung cancer or multiple myeloma who had experienced at least one SRE (defined as radiation to bone, long-bone pathologic fracture, other bone pathologic fracture, surgery to bone or spinal cord compression) were entered into this study.

Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.

Multi-omics research is a key ingredient of data-intensive life sciences research, permitting measurement of biological molecules at different functional levels in the same individual. For a complete picture at the biological systems level, appropriate statistical techniques must however be developed to integrate different 'omics' data sets (e.g.

Contralateral knee effect on self-reported knee-specific function and global functional assessment: data from the Osteoarthritis Initiative.

Objective: To analyze the effect of contralateral knee pain on sensitivity of patient-reported outcomes and objectively measured functional performance tests in subjects with knee osteoarthritis (OA).

Methods: Subjects with discordant knee pain status (i.e.

Longitudinal analysis of whole blood transcriptomes to explore molecular signatures associated with acute renal allograft rejection.

In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype.

Alteration of human blood cell transcriptome in uremia.

Background: End-stage renal failure is associated with profound changes in physiology and health, but the molecular causation of these pleomorphic effects termed "uremia" is poorly understood. The genomic changes of uremia were explored in a whole genome microarray case-control comparison of 95 subjects with end-stage renal failure (n = 75) or healthy controls (n = 20).

Methods: RNA was separated from blood drawn in PAXgene tubes and gene expression analyzed using Affymetrix Human Genome U133 Plus 2.

The economic burden associated with skeletal-related events in patients with bone metastases secondary to solid tumors in Belgium.

Objectives: More than 1.5 million patients worldwide are affected by bone metastases. Patients with bone metastases frequently develop skeletal-related events (SREs, including radiation to bone, non-vertebral fracture, vertebral fracture, surgery to bone, and spinal cord compression) that are associated with high healthcare costs.

A computational pipeline for the development of multi-marker bio-signature panels and ensemble classifiers.

Background: Biomarker panels derived separately from genomic and proteomic data and with a variety of computational methods have demonstrated promising classification performance in various diseases. An open question is how to create effective proteo-genomic panels. The framework of ensemble classifiers has been applied successfully in various analytical domains to combine classifiers so that the performance of the ensemble exceeds the performance of individual classifiers.

DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children.

Background: Allergic inflammation is commonly observed in a number of conditions that are associated with atopy including asthma, eczema and rhinitis. However, the genetic, environmental or epigenetic factors involved in these conditions are likely to be different. Epigenetic modifications, such as DNA methylation, can be influenced by the environment and result in changes to gene expression.