BiomiX, a user-friendly bioinformatic tool for democratized analysis and integration of multiomics data.

Background: Interpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community.

Results: BiomiX tackles the bottleneck in high-throughput omics data analysis, enabling efficient and integrated analysis of multiomics data obtained from two cohorts.

Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus.

Objective: To link changes in the B-cell transcriptome from systemic lupus erythematosus (SLE) patients with those in their macroenvironment, including cellular and fluidic components.

Methods: Analysis was performed on 363 patients and 508 controls, encompassing transcriptomics, metabolomics, and clinical data. B-cell and whole-blood transcriptomes were analysed using DESeq and GSEA.

Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

Purpose: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [F]-FET PET/CT.

Stereotactic body radiation therapy for liver metastases in oligometastatic disease.

Oligometastatic cancers designate cancers in which the number of metastases is less than five, corresponding to a particular biological entity whose prognosis is situated between a localized and metastatic disease. The liver is one of the main sites of metastases. When patients are not suitable for surgery, stereotactic body radiotherapy provides high local control rate, although these data come mainly from retrospective studies, with no phase III study results.

Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers.

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease.

Abnormal B cell glycosylation in autoimmunity: A new potential treatment strategy.

Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are two autoimmune diseases characterised by the production of pathogenic autoreactive antibodies. Their aetiology is poorly understood. Nevertheless, they have been shown to involve several factors, such as infections and epigenetic mechanisms.

External Validation of a Radiomics Model for the Prediction of Complete Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

: Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). All patients treated for a LARC with neoadjuvant CRT and subsequent surgery in two separate institutions between 2012 and 2019 were considered. Both pre-CRT pelvic MRI and CE-CT were mandatory for inclusion.

Metabolic Program of Regulatory B Lymphocytes and Influence in the Control of Malignant and Autoimmune Situations.

Metabolic pathways have been studied for a while in eukaryotic cells. During glycolysis, glucose enters into the cells through the Glut1 transporter to be phosphorylated and metabolized generating ATP molecules. Immune cells can use additional pathways to adapt their energetic needs.

Identification of altered cell signaling pathways using proteomic profiling in stable and progressive chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study was designed to explore CLL B-cells' proteomic profile in order to identify biologic processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were tested at two time points by liquid chromatography-tandem mass spectrometry.

Hyposialylation Must Be Considered to Develop Future Therapies in Autoimmune Diseases.

Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control of pro- or anti-inflammatory immune reactions.

Simulated patient and role play methodologies for communication skills and empathy training of undergraduate medical students.

Background: Verbal and non-verbal communication, as well as empathy are central to patient-doctor interactions and have been associated with patients' satisfaction. Non-verbal communication tends to override verbal messages. The aim of this study was to analyze how medical students use verbal and non-verbal communication using two different educational approaches, student role play (SRP) and actor simulated patient (ASP), and whether the non-verbal behaviour is different in the two different poses.

Epigenetics in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (SjS) is a chronic and systemic autoimmune epithelitis with predominant female incidence, which is characterized by exocrine gland dysfunction. Incompletely understood, the etiology of SjS is multi-factorial and evidence is growing to consider that epigenetic factors are playing a crucial role in its development. Independent from DNA sequence mutations, epigenetics is described as inheritable and reversible processes that modify gene expression.

JAK Inhibitors and Oxidative Stress Control.

Primary Sjögren's syndrome (SjS) is a complex autoimmune epithelitis, with few treatment options, but the use of Janus kinase (JAK) inhibitors is promising because suppression of the JAK/signal transducer and activator of transcription (STAT) pathway improves sicca manifestations. Playing a primary and pathogenic role in disease development, the oxidative stress response is upregulated in activated salivary gland epithelial cells (SGECs) from patients with SjS. Therefore, the aim of this study was to investigate whether JAK inhibitors would suppress SGEC activation in response to an oxidative stress.

The Innate Part of the Adaptive Immune System.

The innate immune response provides a first line of defense against common microorganisms and, for more complex and/or recurring situations where pathogens must be eliminated, an adaptive immune response has emerged and evolved to provide better protection against subsequent infections. However, such dichotomy has to be reevaluated because innate B cells (e.g.

Complement System: a Neglected Pathway in Immunotherapy.

Approved for the treatment of autoimmune diseases, hematological malignancies, and solid cancers, several monoclonal antibodies (mAb) make use of complement in their mechanism of action. Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. Accordingly, new approaches can now be developed with the final objective of increasing the clinical efficacy of mAb.

The regulatory capacity of B cells directs the aggressiveness of CLL.

Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement.

17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study.

Resistance to complement activation, cell membrane hypersialylation and relapses in chronic lymphocytic leukemia patients treated with rituximab and chemotherapy.

The anti-CD20-specific monoclonal antibody rituximab (RTX), in combination with chemotherapy, is commonly used for primary treatment in chronic lymphocytic leukemia (CLL). However, relapses remain important and activation of the complement pathway is one of the mechanisms by which RTX generates the destruction of B cells directly by complement-dependent cytotoxicity (CDC), or indirectly by antibody-dependent cellular phagocytosis. In this study, the RTX capacity to induce CDC was established in 69 untreated CLL patients, this cohort including 34 patients tested before the initiation of RTX-chemotherapy.

Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion.

Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established.

Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]).

[Influence of epigenetic in Sjögren's syndrome].

Sjögren's syndrome (SS) is a systemic autoimmune epithelitis with a major female incidence, and characterized by a dry syndrome, impaired quality of life, visceral involvement, and lymphoma for the most aggressive cases. During this process, epithelial cells acquire the capacity to produce cytokines, chemokines, and autoantigens which can in turn be presented to the immune system. Consequently, this epithelitis is accompanied by lymphocytic infiltrations leading to the formation of pseudo-follicles in which self-reactive B lymphocytes are present.

Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia.

Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients ( = 55) and controls ( = 17). The DNA methylation 'writers' (DNA methyltransferases []), 'readers' (methyl-CpG-binding domain []), 'editors' (ten-eleven translocation []) and 'modulators' () were also evaluated.

Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome.

Objectives: The aetiology of primary Sjögren's syndrome (pSS), also referred to as autoimmune epithelitis, is incompletely understood but includes an epigenetic contribution. Accordingly, the aim of this study was to investigate DNA methylation in salivary gland epithelial cells (SGEC), and to compare results with those publicly available from pSS B and T cells.

Methods: Long-term cultured SGEC were selected to conduct an epigenome-wide association study (EWAS) in patients with pSS with comparison to controls using the HumanMethylation 450 K array from Illumina.

Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by an abnormal expansion of mature B cells in the bone marrow and their accumulation in blood and secondary lymphoid organs. Tumor CLL cells share expression of various surface molecules with many subsets of B cells and have several common characteristics with regulatory B cells (B regs). However, the identification of B regs and their role in CLL remain elusive.

Epigenetic modifications in salivary glands from patients with Sjögren's syndrome affect cytokeratin 19 expression.

Sjögren's syndrome (SS) is a chronic autoimmune epithelitis, and several lines of experiments indicate that multifactorial factors contribute to salivary gland epithelial cells (SGEC) dysfunctions including a combination of environmental factors, lymphocytic infiltrations, genetic predispositions as well as epigenetic defects. Such statement is reinforced by the observation that global DNA methylation (5MeCyt) is altered in minor salivary glands from pSS patients and that such defect is associated cytokeratin 19 (KRT19) overexpression. An epigenetic deregulation of the KRT19 gene was further tested by treating the human salivary gland (HSG) cell line with the DNA demethylating agent 5-azacytidin, and with the histone acetylase inhibitor trichostatin A.

An in silico Approach Reveals Associations between Genetic and Epigenetic Factors within Regulatory Elements in B Cells from Primary Sjögren's Syndrome Patients.

Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets, such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis.