Digitalomics - digital transformation leading to omics insights.

Introduction: Biomarker discovery is increasingly moving from single omics to multiomics, as well as from multi-cell omics to single-cell omics. These transitions have increasingly adopted digital transformation technologies to accelerate the progression from data to insight. Here, we will discuss the concept of 'digitalomics' and how digital transformation directly impacts biomarker discovery.

Glucosamine and Cancer Incidence in Osteoarthritis: A Prevalent New-User Cohort Design.

Objective: Observational studies have associated glucosamine, used to treat joint pain and osteoarthritis, with reductions in cancer incidence, although their study design was affected by selection bias. We assessed this association using a study design that mitigates this selection bias.

Methods: We used the UK Clinical Practice Research Datalink to identify a cohort of patients diagnosed with osteoarthritis during 1995 through 2017.

A Prospective Study of Publicly Funded Molecular Testing of Indeterminate Thyroid Nodules: Canada's Experience.

Context: Indeterminate thyroid nodules (ITNs) lead to diagnostic surgeries in many countries. Use of molecular testing (MT) is endorsed by several guidelines, but costs are limitative, especially in public healthcare systems like in Canada.

Objectives: Primary objective: evaluate the clinical value of Thyroseq® v3 (TSv3) using benign call rate (BCR) in a real-world practice.

Imaging in Rheumatic Immune-related Adverse Events.

Since their introduction, immune checkpoint inhibitors have revolutionized cancer treatment by harnessing the body's own immune system as a defense against tumor growth. The downside of activating the immune system is the development of immune-related adverse events (irAEs), which mimic autoimmune disease of various organ systems. The musculoskeletal system is an uncommon, but substantial one for patients and can lead to long-term pain and disability that affects their quality of life.

The Utility of Laboratory Investigations for the Assessment and Management of Rheumatic Immune Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs).

Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study.

JCO Mosunetuzumab is a CD20xCD3 T-cell-engaging bispecific antibody administered as an off-the-shelf, fixed-duration treatment in an outpatient setting. We report an updated analysis of the durability of response, by investigator assessment, after an overall median follow-up of 3.5 years in patients with relapsed/refractory indolent or aggressive B-cell non-Hodgkin lymphoma (iNHL/aNHL) from the dose-escalation stage of a phase I/II study of mosunetuzumab (ClinicalTrials.

Impact of combined lumbar spine fusion and total hip arthroplasty on spine, pelvis, and hip kinematics during a sit to stand task.

Lumbar fusion is a risk factor for hip dislocation following total hip arthroplasty (THA). The objective was to compare joint/segment angles during sit-stand-sit in participants that had a THA with and without a lumbar fusion. The secondary objective was to compare pain, physical function, disability, and quality of life.

Rheumatoid Arthritis Care Experiences of Black People Living in Canada: A Qualitative Study to Inform Health Service Improvements.

Objective: To understand experiences related to rheumatoid arthritis (RA) care and propose service-level strategies to reduce and mitigate inequities for Black people living in Canada.

Methods: Purposive and respondent driven sampling was used to recruit participants for qualitative interviews to explore population factors relevant to RA care and challenges and facilitators for access to health care services, medications, and enacting preferred treatment plans. Thematic analysis was conducted using the Braun and Clarke method with inductive and deductive coding and critical race theory guiding analysis.

Medicinal Chemistry and NMR Driven Discovery of Novel UDP-glucuronosyltransferase 1A Inhibitors That Overcome Therapeutic Resistance in Cells.

The UDP glucuronosyltransferases (UGT) deactivate many therapeutics via glucuronidation while being required for clearance of normal metabolites and xenobiotics. There are 19 UGT enzymes categorized into UGT1A and UGT2B families based on sequence conservation. This presents a challenge in terms of targeting specific UGTs to overcome drug resistance without eliciting overt toxicity.

Inter-segment coordination amplitude and variability during gait in patients with knee osteoarthritis and asymptomatic adults.

Background: Inter-segment coordination examines the timing and coupling of multiple body segments and provides a complex understanding of how the neuromuscular system controls the body. Research is required to examine if inter-segment coordination during gait differs between individuals with different knee osteoarthritis (OA) severities and asymptomatic adults.

Research Question: Do inter-segment coordination amplitude and between-trial variability during gait differ between individuals with varying levels of knee OA severity and asymptomatic adults?

Methods: This observational, cross-sectional study included participants with mild/moderate knee OA (n = 38), severe knee OA (n = 24), and asymptomatic adults (n = 51).

FGF1 supports glycolytic metabolism through the estrogen receptor in endocrine-resistant and obesity-associated breast cancer.

Background: Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk.

Differential Item Functioning on the Cochin Hand Function Scale Among People With Systemic Sclerosis by Language, Sex, and Disease Subtype: A Scleroderma Patient-Centered Intervention Network (SPIN) Cohort Study.

Objective: To evaluate the degree that the Cochin Hand Function Scale (CHFS) generates scores that are comparable across language, sex, and disease subtype.

Methods: We included participants enrolled in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort who completed the CHFS at their baseline assessment between April 2014 and September 2020. Confirmatory factor analysis (CFA) was used to test unidimensionality, and multiple indicator multiple cause (MIMIC) models were used for differential item functioning (DIF) analysis based on language, sex, and disease subtype.

Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.

Purpose: Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. Genetic testing is currently recommended for adults diagnosed with heritable, idiopathic, anorexigen-, hereditary hemorrhagic telangiectasia-, and congenital heart disease-associated PAH, PAH with overt features of venous/capillary involvement, and all children diagnosed with PAH. Variants in at least 27 genes have putative evidence for PAH causality.

Validity, Reliability, and Differential Item Functioning of English and French Versions of the 10-Item Connor-Davidson Resilience Scale in Systemic Sclerosis: A Scleroderma Patient-Centered Intervention Network Cohort Study.

Objective: Some individuals with systemic sclerosis (SSc) report positive mental health, despite severe disease manifestations, which may be associated with resilience, but no resilience measure has been validated in SSc. This study was undertaken to assess the validity, reliability, and differential item functioning (DIF) between English- and French-language versions of the 10-item Connor-Davidson Resilience Scale (CD-RISC-10) in SSc.

Methods: Eligible participants were enrolled in the Scleroderma Patient-centered Intervention Network Cohort and completed the CD-RISC-10 between August 2022 and January 2023.

Molecular targeting of the UDP-glucuronosyltransferase enzymes in high-eukaryotic translation initiation factor 4E refractory/relapsed acute myeloid leukemia patients: a randomized phase II trial of vismodegib, ribavirin with or without decitabine.

Drug resistance underpins poor outcomes in many malignancies including refractory and relapsed acute myeloid leukemia (R/R AML). Glucuronidation is a common mechanism of drug inactivation impacting many AML therapies, e.g.

Evaluation of Measurement Properties and Differential Item Functioning in the English and French Versions of the University of California, Los Angeles, Loneliness Scale-6: A Scleroderma Patient-Centered Intervention Network (SPIN) Study.

Objective: Loneliness has been associated with poorer health-related quality of life but has not been studied in patients with systemic sclerosis (SSc). The current study was undertaken to examine and compare the psychometric properties of the English and French versions of the University of California, Los Angeles, Loneliness Scale-6 (ULS-6) in patients with SSc during the COVID-19 pandemic.

Methods: This study used baseline cross-sectional data from 775 adults enrolled in the Scleroderma Patient-Centered Intervention Network (SPIN) COVID-19 Cohort.

Contemporary incidence and predictors of left ventricular thrombus in patients with anterior acute myocardial infarction.

Background: The incidence of left ventricular thrombus (LVT) after anterior acute myocardial infarction (AMI) has not been well established in the era of primary percutaneous coronary intervention (pPCI) and potent dual antiplatelet therapy. The objective of this study is to establish the contemporary incidence of LVT in this population, to identify their risk factors, and to examine their association with clinical outcomes.

Methods: A multicenter retrospective cohort study including AMI patients with new-onset antero-apical wall motion abnormalities treated with pPCI between 2009 and 2017 was conducted.

Anti-Valosin-Containing Protein (VCP/p97) Autoantibodies in Inclusion Body Myositis and Other Inflammatory Myopathies.

Objective: The rationale for this study was based on reports that valosin-containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti-VCP antibodies in sIBM and other IIMs.

Mental Health Care Use and Associated Factors in Systemic Sclerosis: A Scleroderma Patient-Centered Intervention Network Cohort Study.

Objective: Systemic sclerosis (SSc) has significant psychosocial implications. We aimed to evaluate the proportion of participants in a large international SSc cohort who used mental health services in a 3-month period and to evaluate demographic, psychological, and disease-specific factors associated with use.

Methods: Baseline data of participants enrolled in the Scleroderma Patient-Centered Intervention Network Cohort were analyzed.