Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept.

The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable and models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy.

Global trends in antibiotic consumption during 2016-2023 and future projections through 2030.

Antibiotic resistance is a global public health threat. Many factors contribute to this issue, with human antibiotic consumption being significant among them. Analyzing trends and patterns in consumption can aid in developing policies to mitigate the burden of antimicrobial resistance and global disparities in access to antibiotics.

Hepatocellular carcinoma associated with progressive intrahepatic familial cholestasis type 2: a case report.

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disorder typically presenting in infancy with cholestasis and rapidly progressing to cirrhosis. PFIC has been associated with an elevated risk of hepatocellular carcinoma (HCC), a neoplasm that is uncommon in children. PFIC type 4 has the strongest link to this type of cancer, although a few cases have also been connected to PFIC2.

Endoscopic transmural resection as an alternative to colorectal surgery after high-risk (non-curative) endoscopic resection.

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal lesions. The full-thickness resection device (FTRD®, Ovesco, Germany) has primarily been used for non-exposed transmural resection of challenging subepithelial or epithelial lesions, where conventional methods may be limited. This technique represents an alternative to surgery in selected patients, and its applications are rapidly expanding.

Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells.

Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch.

Extraskeletal myxoid chondrosarcoma metastasis to a Meckel's diverticulum adenocarcinoma.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain.

Microphysiological pancreas-on-chip platform with integrated sensors to model endocrine function and metabolism.

Pancreatic research is of major importance to advance mechanistic understanding and development of treatment options for diseases such as diabetes mellitus. We present a thermoplastic-based microphysiological system aiming to model the complex microphysiological structure and function of the endocrine pancreas with concurrent real-time read-out capabilities. The specifically tailored platform enables self-guided trapping of single islets at defined locations: β-cells are assembled to pseudo-islets and injected into the tissue chamber using hydrostatic pressure-driven flow.

ObScene database: Semantic congruency norms for 898 pairs of object-scene pictures.

Research on the interaction between object and scene processing has a long history in the fields of perception and visual memory. Most databases have established norms for pictures where the object is embedded in the scene. In this study, we provide a diverse and controlled stimulus set comprising real-world pictures of 375 objects (e.

Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy.

Colorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression.

Hepatic Progenitor Cells in the Form of Ductular Structures within a GIST Liver Metastasis: Supporting a Putative Role in the Hepatic Metastatic Niche.

Introduction: Recent studies have highlighted the presence of hepatic progenitor cells (HPCs) in metastatic liver carcinomas. We provide further evidence of this phenomenon, presenting a case of a gastrointestinal stromal tumour (GIST) liver metastasis with evidence of intra- and peritumoral HPC.

Case Description: A 64-year-old man presented with a gastric mass diagnosed as a high-risk KIT-mutated GIST.

An Immunohistochemical Study of Breast Cancer Brain Metastases: The Role of CD44 and AKT in the Prognosis.

Breast cancer is a major health burden, and up to one-third of patients with breast cancer develop brain metastases, which are linked to a very poor prognosis. Few biomarkers are available to predict the prognosis of patients with metastases. Assessment by immunohistochemistry may be used as a tool to predict the behavior of these tumors.

Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA).

Extensive Phenotypic Characterization of T Cells Infiltrating Liver Metastasis from Colorectal Cancer: A Potential Role in Precision Medicine.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with liver metastasis being its main cause of death. This study harvested fresh biological material from non-tumor and tumor tissue from 47 patients with CRC liver metastasis after surgery, followed by mechanical cellular extraction and stain-lyse-wash direct immunofluorescence technique. Here, 60 different T-cell populations were characterized by flow cytometry.

Combined use of lactoferrin and vitamin D as a preventive and therapeutic supplement for SARS-CoV-2 infection: Current evidence.

Lactoferrin is a multifunctional protein that exhibits anti-inflammatory, immune regulating and anti-infective properties. One of its receptor sites is located on severe acute respiratory syndrome coronavirus 2. The binding of lactoferrin with heparin sulfate proteoglycans may prevent the first contact between the virus and host cells, thus preventing subsequent infection.

Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.

NEU-4438 is a lead for the development of drugs against , which causes human African trypanosomiasis. Optimized with phenotypic screening, targets of NEU-4438 are unknown. Herein, we present a cell perturbome workflow that compares NEU-4438's molecular modes of action to those of SCYX-7158 (acoziborole).

HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia: An immunohistochemical/molecular exploratory study.

Background: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis.

Functional genomics analysis of a phyllospheric Pseudomonas spp with potential for biological control against coffee rust.

Background: Pseudomonas spp. promotes plant growth and colonizes a wide range of environments. During the annotation of a Coffea arabica ESTs database, we detected a considerable number of contaminant Pseudomonas sequences, specially associated with leaves.

Stimuli in 3 Acts: A normative study on action-statements, action videos and object photos.

The study of action observation and imagery, separately and combined, is expanding in diverse research areas (e.g., sports psychology, neurosciences), making clear the need for action-related stimuli (i.

Clinicopathological prognostic factors for gallbladder carcinoma: a retrospective study.

Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical.

Genomic and physiological evaluation of two root associated Pseudomonas from Coffea arabica.

Many Pseudomonas species promote plant growth and colonize a wide range of environments. The annotation of a Coffea arabica ESTs database revealed a considerable number of Pseudomonas sequences. To evaluate the genomic and physiology of Pseudomonas that inhabit coffee plants, fluorescent Pseudomonas from C.