Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype.

Association between bacterial resistance profile and the development of intra-abdominal abscesses in pediatric patients with perforated appendicitis: cohort study.

Purpose: The objective of this study was to determine the association between the presence of a microorganism resistant to the antibiotic used in empirical therapy and the development of intra-abdominal abscesses in children with perforated appendicitis.

Methods: A prospective cohort study was conducted in patients under 18 years of age who underwent laparoscopic appendectomy between November 1, 2019, and September 30, 2020, in whom perforated appendicitis was documented intraoperatively. Peritoneal fluid samples were taken for bacteria culture purposes, and clinical and microbiological data were collected from all patients.

Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine.

Background: Follicular lymphoma (FL), the most common indolent non-Hodgkin's Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses.

Methods: To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability.

A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses.

Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages.

Venetoclax improves CD20 immunotherapy in a mouse model of MYC/BCL2 double-expressor diffuse large B-cell lymphoma.

Background: Approximately one-third of diffuse large B cell lymphoma (DLBCL) patients exhibit co-expression of MYC and BCL2 (double-expressor lymphoma, DEL) and have a dismal prognosis. Targeted inhibition of the anti-apoptotic protein BCL2 with venetoclax (ABT-199) has been approved in multiple B-cell malignancies and is currently being investigated in clinical trials for DLBCL. Whether BCL2 anti-apoptotic function represents a multifaceted vulnerability for DEL-DLBCL, affecting both lymphoma B cells and T cells within the tumor microenvironment, remains to be elucidated.

Predictors of clinical response of esophageal dilatations in pediatric population.

Introduction: Esophageal strictures are a common condition, and pediatric surgeons confront them regularly. Despite being performed very frequently, there ared not studies that clearly identify prognostic factors for pediatric patients.

Methods: Medical records of the children who were taken to esophageal dilatation due to strictures from January 2015 to December 2018 were reviewed.

Cardiac fibroblasts display endurance to ischemia, high ROS control and elevated respiration regulated by the JAK2/STAT pathway.

Cardiovascular diseases are the leading cause of death globally and more than four out of five cases are due to ischemic events. Cardiac fibroblasts (CF) contribute to normal heart development and function, and produce the post-ischemic scar. Here, we characterize the biochemical and functional aspects related to CF endurance to ischemia-like conditions.

Revised International Prognostic Index and genetic alterations are associated with early failure to R-CHOP in patients with diffuse large B-cell lymphoma.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next-generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39.

3D Model Characterization by 2D and 3D Imaging in t(14;18)-Positive B-NHL: Perspectives for In Vitro Drug Screens in Follicular Lymphoma.

Follicular lymphoma (FL) is an indolent B cell lymphoproliferative disorder of transformed follicular center B cells, which accounts for 20-30 percent of all non-Hodgkin lymphoma (NHL) cases. Great advances have been made to identify the most relevant targets for precision therapy. However, no relevant models for in vitro studies have been developed or characterized in depth.

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma.

Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favors tumor growth and, via the secretion of CCL2 and CSF-1, promotes monocyte recruitment, differentiation, and polarization towards an M2-like protumoral phenotype.

Clinical features of amoebic appendicitis in children: A study of 23 cases.

Aim Of The Study: To describe the clinical, surgical, and pathological features of children with acute appendicitis and amebiasis.

Materials And Methods: The medical records of children diagnosed with appendicitis and amebiasis treated at Fundación Hospital la Misericordia were retrospectively reviewed. Patients were classified into two groups according to the location of the amoebas: the amoebic appendicitis (AA) group (when the amoebic infection involved the appendiceal wall), and the appendicitis with incidental amoebiasis (IA) group (when amoebas were only found in the appendiceal lumen).

PI3Kδ inhibition reshapes follicular lymphoma-immune microenvironment cross talk and unleashes the activity of venetoclax.

Despite idelalisib approval in relapsed follicular lymphoma (FL), a complete characterization of the immunomodulatory consequences of phosphatidylinositol 3-kinase δ (PI3Kδ) inhibition, biomarkers of response, and potential combinatorial therapies in FL remain to be established. Using ex vivo cocultures of FL patient biopsies and follicular dendritic cells (FDCs) to mimic the germinal center (n = 42), we uncovered that PI3Kδ inhibition interferes with FDC-induced genes related to angiogenesis, extracellular matrix formation, and transendothelial migration in a subset of FL samples, defining an 18-gene signature fingerprint of idelalisib sensitivity. A common hallmark of idelalisib found in all FL cases was its interference with the CD40/CD40L pathway and induced proliferation, together with the downregulation of proteins crucial for B-T-cell synapses, leading to an inefficient cross talk between FL cells and the supportive T-follicular helper cells (TFH).

Evaluation of concordance among surgeons and pathologists regarding the diagnosis and classification of acute appendicitis in children.

Unlabelled: Acute appendicitis is the most frequent urgent abdominal surgical pathology in children. Therapeutic decisions in patients who have undergone an appendectomy are made based on the macroscopic findings at the moment of surgery. There is high variability between surgical and histopathological findings.

Prognostic Factors Associated with Clinical and Economic Outcomes of Appendectomies in Children: A Multilevel Analysis in a National Retrospective Cohort Study.

Background: Acute appendicitis is the most common acute surgical abdominal pathology in children, and it has a large impact on morbidity and the costs incurred by health care systems. In low- and median-income countries, national information on the clinical and economic outcomes associated with this surgery does not exist. This study aimed to identify and describe the clinical and economic outcomes for children undergoing appendectomy in Colombia's contributory system and to determine the prognostic factors associated with these outcomes.

Characterization of Patients with Minimally Invasive Surgery Converted in a Pediatric Hospital.

Minimally invasive surgery (MIS) in pediatric surgery is now the standard of care for various surgical conditions. We have seen an increase in MIS with some of the procedures requiring intraoperative conversion to open surgery. This is a single-institution retrospective study of patients who underwent MIS between 2009 and 2017 requiring conversion to open surgery.

Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens.

CD38 is expressed in several types of non-Hodgkin lymphoma (NHL) and constitutes a promising target for antibody-based therapy. Daratumumab (Darzalex) is a first-in-class anti-CD38 antibody approved for the treatment of relapsed/refractory (R/R) multiple myeloma (MM). It has also demonstrated clinical activity in Waldenström macroglobulinaemia and amyloidosis.

Mutations in the RAS-BRAF-MAPK-ERK pathway define a specific subgroup of patients with adverse clinical features and provide new therapeutic options in chronic lymphocytic leukemia.

Mutations in genes of the RAS-BRAF-MAPK-ERK pathway have not been fully explored in patients with chronic lymphocytic leukemia. We, therefore, analyzed the clinical and biological characteristics of chronic lymphocytic leukemia patients with mutations in this pathway and investigated the response of primary cells to BRAF and ERK inhibitors. Putative damaging mutations were found in 25 of 452 patients (5.

Reuse of degraded (Jacq.) P. Kumm. substrate by supplementation with wheat bran. Quantitative parameters.

This research work was conducted in order to investigate the agronomic feasibility of by reusing spent substrates previously in crops of the same mushroom. After the physical and chemical characterization of the substrates, we have evaluated quantitative production parameters in one growing season. As base material, the experiment was arranged in wheat straw (WS) and spent substrate (SPS) to generate prepared substrates with the participation of the same, alone, and mixed in different proportions with wheat bran (WB).

Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity.

Background: Excessive apoptosis induces unwanted cell death and promotes pathological conditions. Drug discovery efforts aimed at decreasing apoptotic damage initially targeted the inhibition of effector caspases. Although such inhibitors were effective, safety problems led to slow pharmacological development.

ss3sim: an R package for fisheries Stock Assessment simulation with stock synthesis.

Simulation testing is an important approach to evaluating fishery stock assessment methods. In the last decade, the fisheries stock assessment modeling framework Stock Synthesis (SS3) has become widely used around the world. However, there lacks a generalized and scriptable framework for SS3 simulation testing.

µ-Calpain conversion of antiapoptotic Bfl-1 (BCL2A1) into a prodeath factor reveals two distinct alpha-helices inducing mitochondria-mediated apoptosis.

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor.

Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells.

Although many cancer cells are primed for apoptosis, they usually develop resistance to cell death at several levels. Permeabilization of the outer mitochondrial membrane, which is mediated by proapoptotic Bcl-2 family members such as Bax, is considered as a point of no return for initiating apoptotic cell death. This crucial role has placed Bcl-2 family proteins as recurrent targets for anticancer drug development.

Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence.

Background: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction.

Methodology/principal Findings: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence.