Clinical benefit with tebentafusp in a patient with GNAQ mutant metastatic blue nevus-associated melanoma.

Melanoma arising in association with a blue nevus (BN) is rare but has molecular similarities to uveal melanoma (UM), including GNAQ/11 mutations. Tebentafusp was recently approved for UM based on improved overall survival in a phase 3 study. We hypothesized that tebentafusp may be active in BN-associated melanoma.

Molecular and cellular dynamics of squamous cell carcinomas across tissues.

Squamous cell carcinomas (SCCs), arising from the skin, head and neck, lungs, esophagus, and cervix, are collectively among the most common cancers and a frequent cause of cancer morbidity and mortality. Despite distinct stratified epithelial tissues of origin, converging evidence points toward shared biologic pathways across SCCs. With recent breakthroughs in molecular technologies have come novel SCC treatment paradigms, including immunotherapies and targeted therapy.

Metastatic well differentiated serotonin-producing pancreatic neuroendocrine tumor with carcinoid heart disease: a case report.

Background: Less than two percent of pancreatic neuroendocrine tumors (NETs) produce serotonin. Serotonin can cause carcinoid syndrome and less commonly carcinoid heart disease (CHD). CHD is associated with increased mortality and requires a more aggressive approach.

Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent.

Serum glycomic profile as a predictive biomarker of recurrence in patients with differentiated thyroid cancer.

Purpose: Thyroid cancer recurrence following curative thyroidectomy is associated with increased morbidity and mortality, but current surveillance strategies are inadequate for early detection. Prior studies indicate that tissue glycosylation is altered in thyroid cancer, but the utility of serum glycosylation in thyroid cancer surveillance remains unexplored. We therefore assessed the potential utility of altered serum glycomic profile as a tumor-specific target for disease surveillance in recurrent thyroid cancer.

Network Analysis for Uncovering the Relationship between Host Response and Clinical Factors to Virus Pathogen: Lessons from SARS-CoV-2.

Analysing complex datasets while maintaining the interpretability and explainability of outcomes for clinicians and patients is challenging, not only in viral infections. These datasets often include a variety of heterogeneous clinical, demographic, laboratory, and personal data, and it is not a single factor but a combination of multiple factors that contribute to patient characterisation and host response. Therefore, multivariate approaches are needed to analyse these complex patient datasets, which are impossible to analyse with univariate comparisons (e.

Odds-ratio network for postoperative factors revealing differences in the 2-year longitudinal pattern of satisfaction between women and men after total knee arthroplasty.

Timely and accurate assessments of the factors influencing satisfaction, a key indicator of success in primary total knee arthroplasty (TKA), may help improve TKA outcomes. Here we performed the longitudinal trend analysis of relation between satisfaction and 12 postoperative factors, which positively or negatively influence the patient satisfaction 2 years after TKA. In a real-world registry cohort (women/men: 1121/650), we showed similarities and differences between women and men in the contribution of postoperative factors to satisfaction 2 years after TKA as assessed by odds-ratio-similarity network.

Knee osteoarthritis phenotypes based on synovial fluid immune cells correlate with clinical outcome trajectories.

Background: Knee osteoarthritis (KOA) is a highly heterogeneous disease encompassing a wide range of clinical phenotypes. Phenotypes based on immune cells and protein pattern in synovial fluid (SF) and their relationship to clinical trajectories have not been described.

Objective: To assess phenotypes based on immune cells and protein pattern of SF in KOA.

Determining Normative Values for Cerebrospinal Fluid Profiles in Infants.

Background: Previous studies of reference values for cerebrospinal fluid (CSF) profiles have been limited by small sample size and few exclusion criteria.

Objective: To determine age-specific normative CSF white blood cell count (WBC), glucose, and protein values in infants ≤90 days old.

Methods: Performed a retrospective cross-sectional study of infants ≤90 days old who had a diagnostic lumbar puncture between 2008 and 2016.

Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.

Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods. We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N -Bn-α-GalNAc), as surrogates of protein O-glycosylation. Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.

A theoretical model of health management using data-driven decision-making: the future of precision medicine and health.

Background: The burden of chronic and societal diseases is affected by many risk factors that can change over time. The minimalisation of disease-associated risk factors may contribute to long-term health. Therefore, new data-driven health management should be used in clinical decision-making in order to minimise future individual risks of disease and adverse health effects.

Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks.

The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells.

Resident and elicited murine macrophages differ in expression of their glycomes and glycan-binding proteins.

The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and glycan-binding proteins (GBPs) are integral to macrophage function and may contribute to macrophage diversity, little is known about the factors governing their expression. Here, we provide a resource for characterizing the N-/O-glycomes of various murine peritoneal macrophage sub-populations, demonstrating that glycosylation primarily reflects developmental origin and, to a lesser degree, cellular polarization.

High CXCR3 on Leukemic Cells Distinguishes from in Chronic Lymphocytic Leukemia: Evidence from CD5 and CD5 Clones.

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5 and CD5 neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5 and CD5 subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients ( = 60) subgrouped according to the mutational status ( , = 24; , = 36). CD5 subpopulation showed a high percentage of CXCR3 ( < 0.

Cosmc controls B cell homing.

The molecular mechanisms regulating lymphocyte homing into lymph nodes are only partly understood. Here, we report that B cell-specific deletion of the X-linked gene, Cosmc, and the consequent decrease of protein O-glycosylation, induces developmental blocks of mouse B cells. After transfer into wild-type recipient, Cosmc-null B cells fail to home to lymph nodes as well as non-lymphoid organs.

Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD.

Inflammatory bowel disease (IBD) affects 6.8 million people globally. A variety of factors have been implicated in IBD pathogenesis, including host genetics, immune dysregulation and gut microbiota alterations.

Maintenance Therapy for Cutaneous T-cell Lymphoma After Total Skin Electron Irradiation: Evidence for Improved Overall Survival With Ultraviolet Therapy.

Background: Treatment of cutaneous T-cell lymphoma (CTCL) with total skin electron beam (TSEB) therapy has been associated with deep responses but short progression-free intervals. Maintenance therapy might prolong the response duration; however, limited data assessing the outcomes with maintenance therapy after TSEB are available. We evaluated the effect of maintenance therapy on the outcomes for patients with CTCL receiving TSEB therapy.

Gender Differences in Contribution of Smoking, Low Physical Activity, and High BMI to Increased Risk of Early Reoperation After TKA.

Background: The reliable preoperative identification of patients at a high risk of early reoperations (<2 years after primary surgery) after total knee arthroplasty (TKA) could lead to adjustments of the surgical procedure and counseling, thus lowering the percentage of revision surgeries.

Methods: The unselected cohort consisted of 1885 patients (695 men and 1190 women) who underwent TKA implantation between September 2010 and April 2017 at a single tertiary orthopedic center. Multivariate patient similarity networks were applied to identify patient groups at a high risk of early reoperations based on 25 preoperative parameters.

Identification of Tn antigen O-GalNAc-expressing glycoproteins in human carcinomas using novel anti-Tn recombinant antibodies.

The Tn antigen is a neoantigen abnormally expressed in many human carcinomas and expression correlates with metastasis and poor survival. To explore its biomarker potential, new antibodies are needed that specifically recognize this antigen in tumors. Here we generated two recombinant antibodies to the Tn antigen, Remab6 as a chimeric human IgG1 antibody and ReBaGs6 as a murine IgM antibody and characterized their specificities using multiple biochemical and biological approaches.

Complex karyotype as a predictor of high-risk chronic lymphocytic leukemia: A single center experience over 12 years.

Objectives: A complex karyotype (CK) is considered a poor prognostic marker in chronic lymphocytic leukemia (CLL).

Methods: The study analyzed 644 untreated CLL patients (pts) using conventional/molecular cytogenetics to reveal the presence of a CK and its composition and to assess its predictive value. The mutational status ofTP53 was detected by next generation sequencing.

Inflammation time-axis in aseptic loosening of total knee arthroplasty: A preliminary study.

Objective: Aseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15-20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists.

Design: The inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry.

Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to SLE and SSc.

Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA ( = 36, DAS28 ≥ 3.