Additional Cladribine tablets treatment courses in multiple sclerosis patients. A retrospective observational study in Latin American countries.

The use of additional cladribine tablets treatment courses is becoming an option in patients with multiple sclerosis (MS) showing disease activity after treatment initiation. Despite the availability over the past year of several expert opinion guidance on the subject, there is a need for real-world assessment of the efficacy and safety of cladribine tablets in these patients. Thus, the aim of the present retrospective observational study is to describe the characteristics of patients that received additional treatment courses within the cohort of cladribine tablets-treated MS patients enrolled in the patient support program (PSP) Adveva® in Latin America countries.

Outcome of Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis.

Introduction: Approximately 50% of patients with C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) reach kidney failure 10 years after diagnosis. Because these patients are generally young, the majority will be listed for kidney transplantation (KTx). However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, because they are mainly based on retrospective monocentric studies.

SCRMshaw: Supervised cis-regulatory module prediction for insect genomes.

As the number of sequenced insect genomes continues to grow, there is a pressing need for rapid and accurate annotation of their regulatory component. SCRMshaw is a computational tool designed to predict cis-regulatory modules ("enhancers") in the genomes of various insect species. A key advantage of SCRMshaw is its accessibility.

Identification of a novel downstream midline regulatory element in .

Development of the central nervous system midline depends on the gene ( ). Although regulation has been studied extensively, the fact that an enhancer mediating late embryonic transcription has not been identified suggests that additional regulatory sequences remain unknown. We tested several evolutionarily conserved sequences in the downstream region and isolated , whose midline activity in a reporter gene assay begins later than previously characterized enhancers.

Regulatory genome annotation of 33 insect species.

Annotation of newly sequenced genomes frequently includes genes, but rarely covers important non-coding genomic features such as the -regulatory modules-e.g., enhancers and silencers-that regulate gene expression.

Mechanisms of transcriptional regulation in revealed by allele-specific expression.

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in , by regulatory sequences on the same chromosome, and by acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in -regulatory modules (CRM), but few of these have been identified in mosquitoes.

Case report: Bruton tyrosine kinase inhibitor as therapy for chronic lymphocytic leukemia infiltrating a kidney allograft.

The burden of chronic lymphocytic leukemia (CLL) in the prognosis of solid organ transplant (SOT) recipients seems non-negligible. Whether transplanting a patient with previous CLL is safe or what is the optimal monitoring and treatment management after transplantation is still unclear and only based on few case series and reports. Therefore, we aimed to contribute to this understanding by reporting the first documented case of a clinically significant CLL with biopsy-proven infiltration of the kidney allograft and its successful management with a Bruton tyrosine kinase inhibitor (BTKi).

Mitochondrial Dysfunction in Systemic Lupus Erythematosus with a Focus on Lupus Nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting mostly women of child-bearing age. Immune dysfunction in SLE results from disrupted apoptosis which lead to an unregulated interferon (IFN) stimulation and the production of autoantibodies, leading to immune complex formation, complement activation, and organ damage. Lupus nephritis (LN) is a common and severe complication of SLE, impacting approximately 30% to 40% of SLE patients.

Improved methodology for fixation and preparation of Aedes aegypti embryos.

The yellow fever mosquito Aedes aegypti is a major disease vector and an increasingly popular emerging model research organism. We present here an improved protocol for the collection, fixation, and preparation of A. aegypti embryos for immunohistochemical and in situ hybridization studies.

A new suite of reporter vectors and a novel landing site survey system to study cis-regulatory elements in diverse insect species.

Comparative analyses between traditional model organisms, such as the fruit fly Drosophila melanogaster, and more recent model organisms, such as the red flour beetle Tribolium castaneum, have provided a wealth of insight into conserved and diverged aspects of gene regulation. While the study of trans-regulatory components is relatively straightforward, the study of cis-regulatory elements (CREs, or enhancers) remains challenging outside of Drosophila. A central component of this challenge has been finding a core promoter suitable for enhancer-reporter assays in diverse insect species.

Conserved and novel enhancers in the Aedes aegypti single-minded locus recapitulate embryonic ventral midline gene expression.

Transcriptional cis-regulatory modules, e.g., enhancers, control the time and location of metazoan gene expression.

EnhancerTracker: Comparing cell-type-specific enhancer activity of DNA sequence triplets via an ensemble of deep convolutional neural networks.

Motivation: Transcriptional enhancers - unlike promoters - are unrestrained by distance or strand orientation with respect to their target genes, making their computational identification a challenge. Further, there are insufficient numbers of confirmed enhancers for many cell types, preventing robust training of machine-learning-based models for enhancer prediction for such cell types.

Results: We present , a novel tool that leverages an ensemble of deep separable convolutional neural networks to identify cell-type-specific enhancers with the need of only two confirmed enhancers.

Mechanisms of transcriptional regulation in revealed by allele specific expression.

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in , by regulatory sequences on the same chromosome, and by acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in -regulatory modules (CRM), but few of these have been identified in mosquitoes.

Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment.

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target.

Evaluation of metric and representation learning approaches: Effects of representations driven by relative distance on the performance.

Several deep neural network architectures have emerged recently for metric learning. We asked which architecture is the most effective in measuring the similarity or dissimilarity among images. To this end, we evaluated six networks on a standard image set.

ITGAM rs1143679 Variant in Systemic Lupus Erythematosus Is Associated with Increased Serum Calcification Propensity.

Objectives: CD11B/ITGAM (Integrin Subunit α M) mediates the adhesion of monocytes, macrophages, and granulocytes and promotes the phagocytosis of complement-coated particles. Variants of the ITGAM gene are candidates for genetic susceptibility to systemic lupus erythematosus (SLE). SNP rs1143679 (R77H) of CD11B particularly increases the risk of developing SLE.

IOeRT in retroperitoneal sarcoma: Towards more organ preservation with comparable oncological outcomes.

Background: Retroperitoneal sarcomas (RPS) present a surgical challenge with high rates of local recurrence (LR). We investigated the role of intraoperative electron radiotherapy (IOeRT) in reducing LR after surgical resection of RPS.

Methods: A retrospective analysis of all patients who underwent surgical resection for RPS between 2014 and 2021 at a tertiary academic referral center (n = 172).

Resection of Recurrent Pelvic Soft Tissue Sarcoma: Is the Risk Worth the Reward?

Introduction: Soft tissue sarcomas (STS) of the pelvis present a surgical and oncological challenge. We investigated the outcomes of patients undergoing resection of pelvic sarcomas.

Methods: A retrospective analysis of all patients who underwent surgical resection for STS between 2014 and 2021 at a tertiary academic referral center (n = 172).

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait.

Animal traits develop through the expression and action of numerous regulatory and realizator genes that comprise a gene regulatory network (GRN). For each GRN, its underlying patterns of gene expression are controlled by cis-regulatory elements (CREs) that bind activating and repressing transcription factors. These interactions drive cell-type and developmental stage-specific transcriptional activation or repression.

Multi-state modeling of antibody-antigen complexes with SAXS profiles and deep-learning models.

Antibodies are an established class of human therapeutics. Epitope characterization is an important part of therapeutic antibody discovery. However, structural characterization of antibody-antigen complexes remains challenging.

Reporter gene assays and chromatin-level assays define substantially non-overlapping sets of enhancer sequences.

Background: Transcriptional enhancers are essential for gene regulation, but how these regulatory elements are best defined remains a significant unresolved question. Traditional definitions rely on activity-based criteria such as reporter gene assays, while more recently, biochemical assays based on chromatin-level phenomena such as chromatin accessibility, histone modifications, and localized RNA transcription have gained prominence.

Results: We examine here whether these two types of definitions, activity-based and chromatin-based, effectively identify the same sets of sequences.