Low-pressure continuous dynamic extraction from oak chips combined with passive micro-oxygenation to tune red wine properties.

Static infusion of oak chips in wine is a common practice during wine ageing, aimed at improving sensory properties and stability of wines. The wine/chips contact required to reach the desired effect can last several weeks or months. A low-pressure continuous dynamic (LPCD) extractor in which a closed-circle, low-pressure continuous flow of wine passes through an extraction cell filled with chips, was evaluated as a tool to tune red wine properties in few hours.

The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID.

Introduction: SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

Methods: We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19.

AIEC-dependent pathogenic Th17 cell transdifferentiation in Crohn's disease is suppressed by and deletion.

Mucosal enrichment of the Adherent-Invasive (AIEC) pathotype and the expansion of pathogenic IFNγ-producing Th17 (pTh17) cells have been linked to Crohn's Disease (CD) pathogenesis. However, the molecular pathways underlying the AIEC-dependent pTh17 cell transdifferentiation in CD patients remain elusive. To this aim, we created and functionally screened a transposon AIEC mutant library of 10.

Increasing vaccination coverage among healthcare workers: Active call and mandatory laws. Data from a large general hospital in Southern Italy.

Influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are respiratory pathogens which significantly impact healthcare systems. Seasonal vaccination is recommended for all healthcare workers (HCWs) to reduce the risk for both operators and patients. Puglia, a region in Southern Italy, has been enforcing since 2018 a law mandating influenza vaccination in healthcare workers.

Fine-Tuning the Epigenetic Landscape: Chemical Modulation of Epigenome Editors.

Epigenome editing has emerged as a powerful technique for targeted manipulation of the chromatin and transcriptional landscape, employing designer DNA binding domains fused with effector domains, known as epi-editors. However, the constitutive expression of dCas9-based epi-editors presents challenges, including off-target activity and lack of temporal resolution. Recent advancements of dCas9-based epi-editors have addressed these limitations by introducing innovative switch systems that enable temporal control of their activity.

M-mode ultrasound for assessment of the "tethered fat sign" in children: an easily performed way to certify a dynamic process as a still picture.

Background: Omental infarction is a rare pediatric disease. Ultrasound is a useful modality for a non-invasive pre-operative differential diagnosis between inflammatory conditions (as appendicitis) and omental infarction, especially by detecting immobility of the omentum adhered to the abdominal wall ("tetherd fat sign"). However, this is a dynamic sign that cannot be documented in a static image with B-mode technique.

Feasibility of excitation-emission fluorescence spectroscopy in tandem with chemometrics for quantitation of trans-resveratrol in vine-shoot ethanolic extracts.

Background: trans-Resveratrol (TR) is a well-known phytochemical compound with important biological properties. It can be recovered from agri-food by-products or wastes, such as vine shoots. Once recovered, its concentration should be measured, possibly in a green, non-destructive, and efficient manner.

Epigenetic remodeling to improve the efficacy of immunotherapy in human glioblastoma: pre-clinical evidence for development of new immunotherapy approaches.

Background: Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM.

Application of toasted vine-shoot chips and ultrasound treatment in the ageing of Primitivo wine.

Ageing wine in barrels is an historical practice used to improve the aromatic complexity of wine, but due to the high cost and the long ageing period, alternative approaches have been developed, such as the use of wood chips and ultrasound treatment. The present paper reports the results of an investigation performed on wine (cv. Primitivo).

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

Introduction: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics.

Methods: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery.

Histone-Specific CD4 T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus.

Objective: The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE).

Methods: Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01.

Temporal features of size constancy for perception and action in a real-world setting: A combined EEG-kinematics study.

A stable representation of object size, in spite of continuous variations in retinal input due to changes in viewing distance, is critical for perceiving and acting in a real 3D world. In fact, our perceptual and visuo-motor systems exhibit size and grip constancies in order to compensate for the natural shrinkage of the retinal image with increased distance. The neural basis of this size-distance scaling remains largely unknown, although multiple lines of evidence suggest that size-constancy operations might take place remarkably early, already at the level of the primary visual cortex.

RhoA Is a Crucial Regulator of Myoblast Fusion.

Satellite cells (SCs) are adult muscle stem cells that are mobilized when muscle homeostasis is perturbed. Here we show that RhoA in SCs is indispensable to have correct muscle regeneration and hypertrophy. In particular, the absence of RhoA in SCs prevents a correct SC fusion both to other RhoA-deleted SCs (regeneration context) and to growing control myofibers (hypertrophy context).

Attitudes towards Vaccinations in a National Italian Cohort of Patients with Inflammatory Bowel Disease.

Background: The vaccination status of patients with inflammatory bowel disease (IBD) should be investigated before starting any treatment, and patients should eventually be vaccinated against vaccine-preventable diseases (VPDs). Patients with IBD may have suboptimal vaccination rates. The aim of this study was to evaluate the vaccination coverage, attitude towards vaccinations, and determinants among an Italian cohort of patients with IBD.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution.

Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial.

Association with hypomethylating agents is a promising strategy to improve the efficacy of immune checkpoint inhibitors-based therapy. The NIBIT-M4 was a phase Ib, dose-escalation trial in patients with advanced melanoma of the hypomethylating agent guadecitabine combined with the anti-CTLA-4 antibody ipilimumab that followed a traditional 3 + 3 design (NCT02608437). Patients received guadecitabine 30, 45 or 60 mg/m/day subcutaneously on days 1 to 5 every 3 weeks starting on week 0 for a total of four cycles, and ipilimumab 3 mg/kg intravenously starting on day 1 of week 1 every 3 weeks for a total of four cycles.

Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study.

Background And Aims: Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC.

Structural insights into opposing actions of neurosteroids on GABA receptors.

γ-Aminobutyric acid type A (GABA) receptors mediate fast inhibitory signaling in the brain and are targets of numerous drugs and endogenous neurosteroids. A subset of neurosteroids are GABA receptor positive allosteric modulators; one of these, allopregnanolone, is the only drug approved specifically for treating postpartum depression. There is a consensus emerging from structural, physiological and photolabeling studies as to where positive modulators bind, but how they potentiate GABA activation remains unclear.

Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance.

CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression.

Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires tools to quantitatively modulate protein abundance. Here we present CasTuner, a CRISPR-based toolkit for analog tuning of endogenous gene expression.

Human herpesvirus 6-specific T-cell immunity in allogeneic hematopoietic stem cell transplant recipients.

Human herpesvirus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplant (allo-HSCT) and may lead to severe symptoms. HHV-6-specific immune responses after HSCT are largely unexplored. We conducted a prospective observational study on 208 consecutive adult patients who received allo-HSCT to investigate HHV-6 reactivations and specific immune responses.

iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis.

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models.