Adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of people with resected stage I to III non-small-cell lung cancer and EGFR mutation.

Background: Postoperative adjuvant epidermal growth factor receptor (EGFR) inhibitor osimertinib is the standard care for stage IB-IIIB non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutation, following complete tumour resection, with or without prior platinum-based adjuvant chemotherapy. However, the role of EGFR tyrosine kinase inhibitors (TKIs) in this setting is debated, particularly concerning long-term curative effects versus recurrence delay. Uncertainties persist around treatment duration, harms, and effectiveness across disease stages, prior chemotherapy, or EGFR-sensitising mutation types.

Role of innate immunity in tumor microenvironment of HPV-associated anal cancer: The hypothetical beneficial role of γδ T cells.

HPV infection plays a crucial role in the formation of the tumor microenvironment, especially in tumors associated with the genital tract, anus, and oropharyngeal region. In this manuscript, we will discuss the main genetic characteristics of HPV and its transmission mechanisms, with a specific focus on the expression of the oncogenes E6 and E7. We will also address the major tumors HPV can generate and their associated epidemiology.

The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense.

Pancreatic ductal adenocarcinoma (PDAC) presents a unique challenge for researchers due to its late diagnosis caused by vague symptoms and lack of early detection markers. Additionally, PDAC is characterized by an immunosuppressive microenvironment (TME), making it a difficult tumor to treat. While γδ T cells have shown potential for anti-tumor activity, conflicting studies exist regarding their effectiveness in pancreatic cancer.

Recent Advances in Artificial Intelligence to Improve Immunotherapy and the Use of Digital Twins to Identify Prognosis of Patients with Solid Tumors.

To date, the public health system has been impacted by the increasing costs of many diagnostic and therapeutic pathways due to limited resources. At the same time, we are constantly seeking to improve these paths through approaches aimed at personalized medicine. To achieve the required levels of diagnostic and therapeutic precision, it is necessary to integrate data from different sources and simulation platforms.

Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy.

Natural killer (NK) cells and dendritic cells (DCs) are critical mediators of anti-cancer immune responses. In addition to their individual roles, NK cells and DCs are involved in intercellular crosstalk which is essential for the initiation and coordination of adaptive immunity against cancer. However, NK cell and DC activity is often compromised in the tumor microenvironment (TME).

High fat diet affects the hippocampal expression of miRNAs targeting brain plasticity-related genes.

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD).

Managing low-acuity patients in an Emergency Department through simulation-based multiobjective optimization using a neural network metamodel.

This paper deals with Emergency Department (ED) fast-tracks for low-acuity patients, a strategy often adopted to reduce ED overcrowding. We focus on optimizing resource allocation in minor injuries units, which are the ED units that can treat low-acuity patients, with the aim of minimizing patient waiting times and ED operating costs. We formulate this problem as a general multiobjective simulation-based optimization problem where some of the objectives are expensive black-box functions that can only be evaluated through a time-consuming simulation.

A Closer Look at Histamine in .

The present work intends to provide a closer look at histamine in . This choice is motivated firstly because has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal functions, but also derangements that occur in higher organisms, not excluding humans. Secondly, because histamine has been demonstrated to be a pleiotropic master molecule in pharmacology and immunology, with increasingly recognized roles also in the nervous system.

Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism.

Immunometabolism investigates the intricate relationship between the immune system and cellular metabolism. This study delves into the consequences of mitochondrial frataxin (FXN) depletion, the primary cause of Friedreich's ataxia (FRDA), a debilitating neurodegenerative condition characterized by impaired coordination and muscle control. By using single-cell RNA sequencing, we have identified distinct cellular clusters within the cerebellum of an FRDA mouse model, emphasizing a significant loss in the homeostatic response of microglial cells lacking FXN.

Prospective Validation Study of a Novel Integrated Pathway Based on Clinical Features, Magnetic Resonance Imaging Biomarkers, and MicroRNAs for Early Detection of Prostate Cancer.

Background: Prostate cancer (PCa) is the most diagnosed cancer in men, with an increasing need to integrate noninvasive imaging and circulating microRNAs beyond prostate-specific antigen for screening and early detection.

Objective: To validate magnetic resonance imaging (MRI) biomarkers and circulating microRNAs as triage tests for patients directed to prostate biopsy, and to test different diagnostic pathways to compare their performance on patients' outcome, in terms of unnecessary biopsy avoidance.

Design, Setting, And Participants: A prospective single-center cohort study, enrolling patients with PCa suspicion who underwent MRI, MRI-directed fusion biopsy (MRDB), and circulating microRNAs, was conducted.

A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy.

Background: The ability to increase their degree of pigmentation is an adaptive response that confers pigmentable melanoma cells higher resistance to BRAF inhibitors (BRAFi) compared to non-pigmentable melanoma cells.

Methods: Here, we compared the miRNome and the transcriptome profile of pigmentable 501Mel and SK-Mel-5 melanoma cells vs. non-pigmentable A375 melanoma cells, following treatment with the BRAFi vemurafenib (vem).

Delineating Purinergic Signaling in .

Simplistic models can aid in discovering what is important in the context of normal and pathological behavior. First recognized as a genetic model more than 100 years ago, to date, fruit flies () still remain an astonishingly good laboratory stand-in for scientists to study development and physiology and to investigate the molecular mechanisms of human diseases. This is because fruit flies indeed represent a simplistic model.

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT.

Repurposing Histaminergic Drugs in Multiple Sclerosis.

Multiple sclerosis is an autoimmune disease with a strong neuroinflammatory component that contributes to severe demyelination, neurodegeneration and lesions formation in white and grey matter of the spinal cord and brain. Increasing attention is being paid to the signaling of the biogenic amine histamine in the context of several pathological conditions. In multiple sclerosis, histamine regulates the differentiation of oligodendrocyte precursors, reduces demyelination, and improves the remyelination process.

Vitamin B6 rescues insulin resistance and glucose-induced DNA damage caused by reduced activity of Drosophila PI3K.

The insulin signaling pathway controls cell growth and metabolism, thus its deregulation is associated with both cancer and diabetes. Phosphatidylinositol 3-kinase (PI3K) contributes to the cascade of phosphorylation events occurring in the insulin pathway by activating the protein kinase B (PKB/AKT), which phosphorylates several substrates, including those involved in glucose uptake and storage. PI3K inactivating mutations are associated with insulin resistance while activating mutations are identified in human cancers.

SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells.

Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown.

Comprehensive Analysis of the ILCs and Unconventional T Cells in Virus Infection: Profiling and Dynamics Associated with COVID-19 Disease for a Future Monitoring System and Therapeutic Opportunities.

This review is a comprehensive analysis of the effects of SARS-CoV-2 infection on Unconventional T cells and innate lymphoid cells (ILCs). COVID-19 affected patients show dysregulation of their adaptive immune systems, but many questions remain unsolved on the behavior of Unconventional cells and ILCs during infection, considering their role in maintaining homeostasis in tissue. Therefore, we highlight the differences that exist among the studies in cohorts of patients who in general were categorized considering symptoms and hospitalization.

Integro-differential approach for modeling the COVID-19 dynamics - Impact of confinement measures in Italy.

The COVID-19 pandemic has overwhelmed the life and security of most of the world countries, and especially of the Western countries, without similar experiences in the recent past. In a first phase, the response of health systems and governments was disorganized, but then incisive, also driven by the fear of a new and dramatic phenomenon. In the second phase, several governments, including Italy, accepted the doctrine of "coexistence with the virus" by putting into practice a series of containment measures aimed at limiting the dramatic sanitary consequences while not jeopardizing the economic and social stability of the country.

Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing.

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs).

Novel P2X7 Antagonist Ameliorates the Early Phase of ALS Disease and Decreases Inflammation and Autophagy in SOD1-G93A Mouse Model.

Amyotrophic lateral sclerosis (ALS) is a disease with a resilient neuroinflammatory component caused by activated microglia and infiltrated immune cells. How to successfully balance neuroprotective versus neurotoxic actions through the use of anti-inflammatory agents is still under debate. There has been a boost of awareness regarding the role of extracellular ATP and purinergic receptors in modulating the physiological and pathological mechanisms in the nervous system.

SWIMmeR: an R-based software to unveiling crucial nodes in complex biological networks.

Summary: We present SWIMmeR, an open-source version of its predecessor SWIM (SWitchMiner) that is a network-based tool for mining key (switch) genes that are associated with intriguing patterns of molecular co-abundance and may play a crucial role in phenotypic transitions in various biological settings. SWIM was originally written in MATLAB®, a proprietary programming language that requires the purchase of a license to install, manipulate, operate and run the software. Over the last years, SWIM has sparked a widespread interest within the scientific community thanks to the promising results obtained through its application in a broad range of phenotype-specific scenarios, spanning from complex diseases to grapevine berry maturation.

A mathematical model of cardiovascular dynamics for the diagnosis and prognosis of hemorrhagic shock.

A variety of mathematical models of the cardiovascular system have been suggested over several years in order to describe the time-course of a series of physiological variables (i.e. heart rate, cardiac output, arterial pressure) relevant for the compensation mechanisms to perturbations, such as severe haemorrhage.

A data-driven model of the COVID-19 spread among interconnected populations: epidemiological and mobility aspects following the lockdown in Italy.

An epidemic multi-group model formed by interconnected SEIR-like structures is formulated and used for data fitting to gain insight into the COVID-19 dynamics and into the role of non-pharmaceutical control actions implemented to limit the infection spread since its outbreak in Italy. The single submodels provide a rather accurate description of the COVID-19 evolution in each subpopulation by an extended SEIR model including the class of asymptomatic infectives, which is recognized as a determinant for disease diffusion. The multi-group structure is specifically designed to investigate the effects of the inter-regional mobility restored at the end of the first strong lockdown in Italy (June 3, 2020).