Hepatotoxicity in Cancer Immunotherapy: Diagnosis, Management, and Future Perspectives.

Cancer immunotherapy, particularly immune checkpoint inhibitors, has positively impacted oncological treatments. Despite its effectiveness, immunotherapy is associated with immune-related adverse events (irAEs) that can affect any organ, including the liver. Hepatotoxicity primarily manifests as immune-related hepatitis and, less frequently, cholangitis.

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation.

Antibiotic resistance of isolates from different water sources in Mbarara, Uganda.

is widely used as an indicator of recent faecal pollution of water. Most strains are commensals; however, isolates in water samples have been shown to carry antibiotic resistance determinants. In total, 47 were isolated from selected drinking water sources in Mbarara, Uganda.

Occurrence of Uncultured spp. in Treated Wastewater Effluent and Its Impact on Human Health (SCA.Re.S Project).

Wastewater treatment plants (WWTPs) provide optimal conditions for the environmental spread of . As part of the Evaluation of Sanitary Risk Related to the Discharge of Wastewater to the Ground (SCA.Re.

Factors Influencing Microbial Contamination of Groundwater: A Systematic Review of Field-Scale Studies.

Pathogenic microorganisms released onto the soil from point or diffuse sources represent a public health concern. They can be transported by rainwater that infiltrates into subsoil and reach the groundwater where they can survive for a long time and contaminate drinking water sources. As part of the SCA.

RICTOR/mTORC2 downregulation in BRAF melanoma cells promotes resistance to BRAF/MEK inhibition.

Background: The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM.

Methods: After analyzing The Cancer Genome Atlas MM patients' database to explore both overall survival and molecular signatures as a function of intra-tumor RICTOR levels, we investigated the effects of RICTOR downregulation in BRAF MM cell lines on their response to BRAF/MEKi.

Biology System Description Language (BiSDL): a modeling language for the design of multicellular synthetic biological systems.

Background: The Biology System Description Language (BiSDL) is an accessible, easy-to-use computational language for multicellular synthetic biology. It allows synthetic biologists to represent spatiality and multi-level cellular dynamics inherent to multicellular designs, filling a gap in the state of the art. Developed for designing and simulating spatial, multicellular synthetic biological systems, BiSDL integrates high-level conceptual design with detailed low-level modeling, fostering collaboration in the Design-Build-Test-Learn cycle.

GI genius endoscopy module: a clinical profile.

Introduction: The identification of early-stage colorectal cancers (CRC) and the resection of pre-cancerous neoplastic lesions through colonoscopy allows to decrease both CRC incidence and mortality. However, colonoscopy miss rates up to 26% for adenomas and 9% for advanced adenomas have been reported. In recent years, artificial intelligence (AI) systems have been emerging as easy-to-use tools, potentially lowering the risk of missing lesions.

Validation of the structured interview section of the penn computerized adaptive test for neurocognitive and clinical psychopathology assessment (CAT GOASSESS).

Large-scale studies and burdened clinical settings require precise, efficient measures that assess multiple domains of psychopathology. Computerized adaptive tests (CATs) can reduce administration time without compromising data quality. We examined feasibility and validity of an adaptive psychopathology measure, GOASSESS, in a clinical community-based sample (N = 315; ages 18-35) comprising three groups: healthy controls, psychosis, mood/anxiety disorders.

Cross-Omic Transcription Factor Analysis: An Insight on Transcription Factor Accessibility and Expression Correlation.

It is well known how sequencing technologies propelled cellular biology research in recent years, providing incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to simultaneously perform the mentioned sequencing modalities on the same cells.

Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer.

Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation.

Benchmark Software and Data for Evaluating CRISPR-Cas9 Experimental Pipelines Through the Assessment of a Calibration Screen.

Genome-wide genetic screens using CRISPR-guide RNA libraries are widely performed in mammalian cells to functionally characterize individual genes and for the discovery of new anticancer therapeutic targets. As the effectiveness of such powerful and precise tools for cancer pharmacogenomics is emerging, tools and methods for their quality assessment are becoming increasingly necessary. Here, we provide an R package and a high-quality reference data set for the assessment of novel experimental pipelines through which a single calibration experiment has been executed: a screen of the HT-29 human colorectal cancer cell line with a commercially available genome-wide library of single-guide RNAs.

Validation of the cognitive section of the Penn computerized adaptive test for neurocognitive and clinical psychopathology assessment (CAT-CCNB).

Background: The Penn Computerized Neurocognitive Battery is an efficient tool for assessing brain-behavior domains, and its efficiency was augmented via computerized adaptive testing (CAT). This battery requires validation in a separate sample to establish psychometric properties.

Methods: In a mixed community/clinical sample of N = 307 18-to-35-year-olds, we tested the relationships of the CAT tests with the full-form tests.

p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells.

p140Cap is an adaptor protein involved in assembling multi-protein complexes regulating several cellular processes. p140Cap acts as a tumor suppressor in breast cancer (BC) and neuroblastoma patients, where its expression correlates with a better prognosis. The role of p140Cap in tumor metabolism remains largely unknown.

Scoring systems for risk stratification in upper and lower gastrointestinal bleeding.

Several scoring systems have been developed for both upper and lower GI bleeding to predict the bleeding severity and discriminate between low-risk patients, who may be suitable for outpatient management, and those who would likely need hospital-based interventions and are at high risk for adverse outcomes. Risk scores created to identify low-risk patients (namely the Glasgow Blatchford Score and the Oakland score) showed very good discriminative performances and their implementation has proven to be effective in reducing hospital admissions and healthcare burden. Conversely, the performances of risk scores in identifying specific adverse events to define high-risk patients are less accurate, and whether their integration into routine clinical practice has a tangible impact on patient management remains unproven.

Neuronal Spike Shapes (NSS): A straightforward approach to investigate heterogeneity in neuronal excitability states.

The mammalian brain exhibits a remarkable diversity of neurons, contributing to its intricate architecture and functional complexity. The analysis of multimodal single-cell datasets enables the investigation of cell types and states heterogeneity. In this study, we introduce the Neuronal Spike Shapes (NSS), a straightforward approach for the exploration of excitability states of neurons based on their Action Potential (AP) waveforms.

RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because of subsequent waves and long-term consequences of great concern. Here, we chart the molecular basis of COVID-19 pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproducts (RAGE) pathway in monocytes.

Validation in type 2 diabetes of a metabolomic signature of all-cause mortality.

Context: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed.

Objective: To validate in type 2 diabetes the association with all-cause mortality of a 14-metabolite score (14-MS) previously reported in the general population and whether this score can be used to improve well-established mortality prediction models.

High-throughput screening as a drug repurposing strategy for poor outcome subgroups of pediatric B-cell precursor Acute Lymphoblastic Leukemia.

Although a great cure rate has been achieved for pediatric BCP-ALL, approximately 15% of patients do not respond to conventional chemotherapy and experience disease relapse. A major effort to improve the cure rates by treatment intensification would result in an undesirable increase in treatment-related toxicity and mortality, raising the need to identify novel therapeutic approaches. High-throughput (HTP) drug screening enables the profiling of patients' responses in vitro and allows the repurposing of compounds currently used for other diseases, which can be immediately available for clinical application.

Peripheral Blood and Nasopharyngeal Swab MiRNA-155 Expression in Infants with Respiratory Syncytial Virus Infection.

Introduction: MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as antiviral responses, but its role during respiratory syncytial virus (RSV) infections is not known. The objective of this study was to investigate the expression of miR-155 using pharyngeal swabs and peripheral blood in infants with RSV infection and uninfected controls.

Methods: A prospective age-matched study was conducted in primary care in Torino from 1 August 2018 to 31 January 2020.