Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort.

Background And Aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis.

Methods: HCC occurrence was evaluated by Kaplan-Meier analysis.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

Study Question: How should fertility-sparing treatment of patients with endometrial carcinoma be performed?

Summary Answer: Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma.

What Is Known Already: The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting.

Probiotics and Prebiotics: Any Role in Menopause-Related Diseases?

Purpose Of Review: The aim of this review is to provide an overview of the menopause-related changes in microbiota and their role in the pathogenesis of menopause-related diseases. In addition, evidence on probiotic supplementation as a therapeutic strategy is discussed.

Recent Findings: The human microbiota is a complex community that lives in a mutualism relationship with the host.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.

Effects of a probiotic suspension Symprove™ on a rat early-stage Parkinson's disease model.

An increasing number of studies in recent years have focused on the role that the gut may play in Parkinson's Disease (PD) pathogenesis, suggesting that the maintenance of a healthy gut may lead to potential treatments of the disease. The health of microbiota has been shown to be directly associated with parameters that play a potential role in PD including gut barrier integrity, immunity, function, metabolism and the correct functioning of the gut-brain axis. The gut microbiota (GM) may therefore be employed as valuable indicators for early diagnosis of PD and potential targets for preventing or treating PD symptoms.

Clinical features and metabolic complications for non-alcoholic fatty liver disease (NAFLD) in youth with obesity.

Pediatric obesity has become in the last forty years the most common metabolic disease in children and adolescents affecting about 25% of the pediatric population in the western world. As obesity worsens, a whole-body insulin resistance (IR) occurs. This phenomenon is more pronounced during adolescence, when youth experience a high degree of insulin resistance due the production of growth hormone.

Integrative multi-omics networks identify PKCδ and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy.

Despite producing a panoply of potential cancer-specific targets, the proteogenomic characterization of human tumors has yet to demonstrate value for precision cancer medicine. Integrative multi-omics using a machine-learning network identified master kinases responsible for effecting phenotypic hallmarks of functional glioblastoma subtypes. In subtype-matched patient-derived models, we validated PKCδ and DNA-PK as master kinases of glycolytic/plurimetabolic and proliferative/progenitor subtypes, respectively, and qualified the kinases as potent and actionable glioblastoma subtype-specific therapeutic targets.

Identification of 2-Aminoacyl-1,3,4-thiadiazoles as Prostaglandin E and Leukotriene Biosynthesis Inhibitors.

The application of a multi-step scientific workflow revealed an unprecedented class of PGE/leukotriene biosynthesis inhibitors with activity. Specifically, starting from a combinatorial virtual library of ∼4.2 × 10 molecules, a small set of compounds was identified for the synthesis.

Optimizing choices and sequences in the diagnostic-therapeutic landscape of advanced triple-negative breast cancer: An Italian consensus paper and critical review.

Triple-negative (TN) metastatic breast cancer (mBC) represents the most challenging scenario withing mBC framework, and it has been only slightly affected by the tremendous advancements in terms of drug availability and survival prolongation we have witnessed in the last years for advanced disease. However, although chemotherapy still represents the mainstay of TN mBC management, in the past years, several novel effective agents have been developed and made available in the clinical practice setting. Within this framework, a panel composed of a scientific board of 17 internationally recognized breast oncologists and 42 oncologists working within local spoke centers, addressed 26 high-priority statements, including grey areas, regarding the management of TN mBC.

Lipidomic alterations in human saliva from cystic fibrosis patients.

Cystic fibrosis is a hereditary metabolic disorder characterized by impaired traffic of chloride ions and water through membranes of the respiratory and gastrointestinal, that causes inadequate hydration of airway surfaces, dehydrated mucous secretions and a high-sodium chloride sweat. Although the classical presentation of the condition is well known, a better characterization of metabolic alterations related is need. In particular, the metabolic composition alterations of biological fluids may be influence by the disease state and could be captured as putative signature to set targeted therapeutic strategies.

Homo sapiens and Neanderthals share high cerebral cortex integration into adulthood.

There is controversy around the mechanisms that guided the change in brain shape during the evolution of modern humans. It has long been held that different cortical areas evolved independently from each other to develop their unique functional specializations. However, some recent studies suggest that high integration between different cortical areas could facilitate the emergence of equally extreme, highly specialized brain functions.

Frailty and hyperactive delirium in hospitalized older patients with COVID-19: an insight from GeroCovid registry.

Background: Delirium is an acute neuropsychiatric condition associated with unfavourable outcomes, frequent in older hospitalized people. In the context of the SARS-CoV-2 pandemic, few studies have specifically focused on the inflammatory status of older, frail patients with hyperactive delirium (HD) hospitalized for COVID-19.

Aim: To identify biological correlates of HD at hospital admission and to assess the independent effect of delirium and physical frailty on in-hospital mortality.

Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei.

Identification of 2,4,5-trisubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one-based small molecules as selective BRD9 binders.

Targeting bromodomain-containing protein 9 (BRD9) represents a promising strategy for the development of new agents endowed with anticancer properties. With this aim, a set of 2,4,5-trisubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one-based compounds was investigated following a combined approach that relied on in silico studies, chemical synthesis, biophysical and biological evaluation of the most promising items. The protocol was initially based on molecular docking experiments, accounting a library of 1896 potentially synthesizable items tested in silico against the bromodomain of BRD9.

Effect of Different Coffee Brews on Tryptophan Metabolite-Induced Cytotoxicity in HT-29 Human Colon Cancer Cells.

Coffee consumption positively influences colon health. Conversely, high levels of tryptophan metabolites such as skatole released from intestinal putrefactive fermentation in the presence of excessive dietary animal protein intake, and gut microbiota alterations, may have several adverse effects, including the development of colorectal cancer. Therefore, this study aimed to elucidate the potential protective effects of coffee in the presence of different skatole levels.

European Association for the Study of Obesity Position Statement on Medical Nutrition Therapy for the Management of Overweight and Obesity in Adults Developed in Collaboration with the European Federation of the Associations of Dietitians.

Introduction: Obesity affects nearly 1 in 4 European adults increasing their risk for mortality and physical and psychological morbidity. Obesity is a chronic relapsing disease characterized by abnormal or excessive adiposity with risks to health. Medical nutrition therapy based on the latest scientific evidence should be offered to all Europeans living with obesity as part of obesity treatment interventions.

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles.

is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity.

Pleiotropic genetic factors (e.g., DNA polymorphisms) may be involved in the initiation of neuroblastoma (NB) and coronary artery disease (CAD) given their common origin from defects in neural crest development.

Untargeted and targeted LC-MS and data processing workflow for the comprehensive analysis of oligopeptides from cyanobacteria.

Cyanobacteria produce a plethora of structurally diverse bioactive secondary metabolites, including cyanotoxins which pose a serious threat to humans and other living organisms worldwide. Currently, a wide variety of mass spectrometry-based methods for determination of microcystins (MCs), the most commonly occurring and studied class of cyanotoxins, have been developed and employed for research and monitoring purposes. The scarcity of commercially available reference materials, together with the ever-growing range of mass spectrometers and analytical approaches, make the accuracy of quantitative analyses a critical point to be carefully investigated in view of a reliable risk evaluation.

Boosting lung accumulation of gallium with inhalable nano-embedded microparticles for the treatment of bacterial pneumonia.

The potential of intra-venous gallium nitrate (GaN) administration against Pseudomonas aeruginosa pneumonia was recently demonstrated in mice and in cystic fibrosis (CF) patients. Likewise, the added value of direct lung delivery of Ga(III) has been shown in rats. Therefore, the design of a drug delivery system specifically engineered for Ga(III) inhalation is imperative to improve its accumulation in lungs.

Fluorouracil and dose-dense adjuvant chemotherapy in patients with early-stage breast cancer (GIM2): end-of-study results from a randomised, phase 3 trial.

Background: Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.

Methods: In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18-70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0-1 from 81 hospitals in Italy.