Experiencing Authenticity of the House Museums in Hybrid Environments

The paper presents an existing scenario related to the advanced integration of digital technologies in the field of house museums, based on the critical literature and applied experimentation. House museums are a particular type of heritage site, in which is highlighted the tension between the evocative capacity of the spaces and the requirements for preservation. In this dimension, the use of a seamless approach amplifies the atmospheric component of the space, superimposing, through hybrid digital technologies, an interactive, context-driven layer in an open dialogue between digital and physical. The methodology moves on the one hand from the literature review, framing the macro themes of research, and on the other from the overview of case studies, selected on the basis of the experiential value of the space. The analysis of the selected cases followed as criteria: the formal dimension of the technology; the narrative plot, as storytelling of socio-cultural atmosphere or identification within the intimate story; and the involvement of visitors as individual immersion or collective rituality. The paper aimed at outlining a developmental panorama in which the integration of hybrid technologies points to a new seamless awareness within application scenarios as continuous and work-in-progress challenges

Reduced intensity conditioning allogeneic transplant for advanced chronic lymphocytic leukemia

We report the preliminary results of 12 patients with advanced stage chronic lymphocytic leukemia (CLL) transplanted following reduced intensity conditioning (RIC. With a median of 22 months of follow-up, 9 patients are alive and 3 have died of progressive disease, graft-versus-host disease (GVHD) or toxic hepatitis. Acute grade I-III GVHD occurred in 33% of patients and chronic GVHD in 50%. Eight of the 12 patients achieved a complete remission (CR) and 2 patients a partial remission (PR). Donor lymphocyte infusion was effective in 6 patients. Event-free survival, progression-free survival and non-relapse mortality at 3 years were 68%, 42% and 16%, respectively. Our results show successful immunomodulation and reduction in tumor burden in high risk CL

Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice

Pharmacological treatments for advanced hepatocellular carcinoma (HCC) have a partial efficacy. Augmented Na+ content and water retention are observed in human cancers and offer unexplored targets for anticancer therapies. Na+ levels are evaluated upon treatments with the antibiotic cation ionophore Monensin by fluorimetry, ICP-MS, Na-23-MRI, NMR relaxometry, confocal or time-lapse analysis related to energy production, water fluxes and cell death, employing both murine and human HCC cell lines, primary murine hepatocytes, or HCC allografts in NSG mice. Na+ levels of HCC cells and tissue are 8-10 times higher than that of healthy hepatocytes and livers. Monensin further increases Na+ levels in HCC cells and in HCC allografts but not in primary hepatocytes and in normal hepatic and extrahepatic tissue. The Na+ increase is associated with energy depletion, mitochondrial Na+ load and inhibition of O-2 consumption. The Na+ increase causes an enhancement of the intracellular water lifetime and death of HCC cells, and a regression and necrosis of allograft tumors, without affecting the proliferating activity of either HCCs or healthy tissues. These observations indicate that HCC cells are, unlike healthy cells, energetically incapable of compensating and surviving a pharmacologically induced Na+ load, highlighting Na+ homeostasis as druggable target for HCC therapy.The ionophore monensin is shown to have cancer-selective cytotoxic action by selectively increasing the sodium content in cultured hepatocellular carcinoma cells (HCC) and allografts, highlighting the sensitivity of HCC cells to pharmacologically induced Na+ load

Terminal ileum ileoscopy and histology in patients undergoing high-definition colonoscopy with virtual chromoendoscopy for chronic nonbloody diarrhea : a prospective, multicenter study

Background and aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD. Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis. Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 \ub1 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient. Conclusions: Retrograde ileoscopy with HD + DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques

In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a treatment option for patients with hematopoietic malignancies that is hampered by treatment-related morbidity and mortality, in part the result of opportunistic infections, a direct consequence of delayed T-cell recovery. Thymic output can be improved by facilitation of thymic immigration, known to require precommitment of CD34(+) cells. We demonstrate that Delta-like ligand-mediated predifferentiation of mobilized CD34(+) cells in vitro results in a population of thymocyte-like cells arrested at a T/natural killer (NK)-cell progenitor stage. On intrahepatic transfer to Rag2(-/-)gamma(c)(-/-) mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor-alphabeta(+) mature T cells considerably faster than animals transplanted with noncultured CD34(+) cells. This finding creates the opportunity to develop an early T-cell reconstitution therapy to combine with HSCT

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. Ki67 at diagnosis did not discriminate responders to PARPi

Bone marrow endothelial progenitors are defective in systemic sclerosis

Objective. Vascular abnormalities represent the main component of the pathobiol. of systemic sclerosis (SSc), progressing from structural derangements of the microcirculation with abortive neoangiogenesis to final vessel loss. Since circulating endothelial progenitor cells (EPCs) are important in the vascular repair process, we undertook this study to examine their nos. in the peripheral blood (PB) of SSc patients and to evaluate whether their status is related to impaired quant. and/or qual. aspects of the bone marrow (BM) microenvironment. Methods. Circulating EPCs from 62 SSc patients were evaluated by flow cytometry and characterized as CD45 neg. and CD133 pos. BM EPCs, identified as CD133 pos., were isolated from 14 SSc patients and grown to induce endothelial differentiation. In addn., progenitor nos. and functional properties of hematopoietic and stromal compartments were analyzed by various assays. Results. We found that EPCs were detectable in the PB of patients with SSc, and their no. was significantly increased in patients with early-stage disease but not in those with late-stage disease. All of the examd. BM samples contained reduced nos. of EPCs and stromal cells, both of which were functionally impaired. Both endothelial and stromal progenitors expressed vascular endothelial growth factor receptor, indicating that BM is strongly induced to differentiate into the endothelial lineage; furthermore, only BM EPCs from patients with early disease led to endothelial differentiation in vitro. Conclusion. This study provides the first demonstration that in SSc, there is a complex impairment in the BM microenvironment involving both the endothelial and mesenchymal stem cell compartments and that this impairment might play a role in defective vasculogenesis in scleroderma. [on SciFinder (R)