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  • Personalized immune intervention to release and redirect the T cells against a tumor has shown substantial progress in aggressive tumors such as melanoma and lung cancer, despite the fact that predictors of sustained response are still unclear. Data on less common histotypes are scanty. Among soft tissue sarcomas, uterine leiomyosarcomas (ULMS) have a dire prognosis, yet therapeutic advances are needed in order to improve the actual treatment. Immune checkpoint inhibitor therapy has been applied to exceptionally few cases, of which the immune cell composition was not examined in detail. We analyzed in situ the inflammatory infiltrate of 21 untreated ULMS in high-dimensional, single cell phenotyping on routinely processed tissue, directed at the characterization of lymphoid cells and macrophages. T-lymphoid cells displayed a composite phenotype common to all tumors, suggestive of antigen-exposure; in about half of the cases containing sufficient lymphocytes, we found evidence of exhaustion and a CD8+ TCF7+ phenotype, this latter associated with T-cell reactivation. To the contrary, myelomonocytic cells had case-specific individual combinations of phenotypes and subsets. We identified five distinct monocyte-macrophage cell types: histiocytes, phagocytes, tumor-associated macrophages, inflammatory monocytes and myelomonocytic cells of undefined phenotype. Immunosuppressive molecules (TIM3, B7H3, VISTA, PD1, PDL1) were heterogeneously expressed in inflammatory and endothelial cells. The heterogeneity and phenotype of the monocyte-macrophage population may represents a challenge for which we provide an initial understanding.
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  • Dataset and materials for the rTMS study "Keeping order in the brains: the supramarginal gyrus and serial order in short-term memory". In the "Experiment folders" there are the E-Prime script of the tasks and the stimuli used. In the "Database and all anlysis" folder, there is the anonymus excel database of all 4 experiments and the Statistica workbook with all the analyses conducted and reported in the paper.
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  • Pipelines for CellProfiler mask generation, creation of heatmaps with R from Phenograph .csv data, .csv data exported from HistoCAT after segmentation and analysis. Refers to The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping. by Bolognesi MM et al.
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  • Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect β-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer's disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.
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  • Purpose: The association between serum uric acid (SUA) and pulse wave velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. The purpose of this study was to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies. Materials and methods: Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed. Results: Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: −0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association. Conclusion: The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cf- and ba-PWV in hypertensive subjects.
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  • Objective: To assess acceptability, efficacy, and short- and medium-term complications of vaginal misoprostol therapy for the treatment of first trimester miscarriage. Study design: A prospective cohort study including women admitted to the Unit of Obstetrics, MBBM Foundation, San Gerardo Hospital (Monza, Italy) for medical or surgical treatment of first trimester miscarriage between October 2014 and March 2018. As per Institutional protocol, patients in the medical therapy group received 800 µg of misoprostol vaginally. A second dose could be considered 3 days after the first administration if that was ineffective. Surgical treatment consisted of uterine vacuum aspiration. Success of misoprostol treatment was defined as the expulsion of the gestational sac with no need for subsequent surgery. Results: During the study period, 967 patients were diagnosed with first trimester miscarriage and were included in the study. Of these, 514 (53.2%) women were eligible for and consented to medical therapy. Surgical treatment was performed in the remaining 453 (46.8%) patients due to either medical contraindication to misoprostol or patient’s choice. Acceptance of misoprostol as first therapeutic choice increased over time, becoming the preferred treatment after approximately 18 months of use in clinical practice. One dose of misoprostol was successful in 69.8% (n = 359) of patients, whereas 20 women required urgent surgery for bleeding (n = 19) or suspected infection (n = 1). Among the remaining 135 patients, 20 (14.8%) refused the second dose of misoprostol and opted for surgery. Expulsion of the gestational sac was obtained in 74 additional cases who completed the medical protocol, for an overall success rate of 87.7% (433/494). The majority of women receiving misoprostol did not experience any short-term complication (92.0%) or side effect (93.8%). Eight (1.6%) cases requiring delayed surgery (hysteroscopy or vacuum aspiration) for retained product of conception were identified at the postmedical treatment follow up, thus leading to an actual success rate of misoprostol of 86.0% (n = 425). Conclusions: This is the first study assessing the acceptability, efficacy, and complication rate of medical management of first trimester miscarriage in an Italian tertiary care center. Our results confirm that misoprostol alone is an effective as well as a safe therapeutic option for the treatment of first trimester miscarriage.
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  • Additional file 1. Online Methodology and eTables. Expanded Methods and Materials. eTable 1: Comorbidities and risk factors in study population (n = 2005), stratified by arterial oxygenation on day 1. eTable 2. Characteristics of patients with sustained normoxemia and sustained hyperoxemia. eTable 3: Characteristics at ARDS onset and clinical outcomes in matched sample (n = 354) of patients with sustained normoxemia and with sustained hyperoxemia. eTable 4. Characteristics at ARDS onset and clinical outcomes in matched sample (n = 646) of patients with normoxemia and with excess oxygen use at day 1.
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  • Appendix 1, Table S1, Table S2, − Table S3. (DOCX 40 kb)
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  • Additional file 1: Supplementary Movie 1. High-resolution imaging of phantom 30E017 at baseline (October 2015, Left panel) and at two years post manufacturing (Right panel). (MP4 69,750 kb)
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  • Purpose: Cuffless blood pressure (CL-BP) measurements are believed to be a potentially alternative to cuff-occlusion-based (C-BP) measurement. A new cuffless device was developed for ambulatory BP monitoring. We assessed the accuracy of a new CL-BP device compared to a standard oscillatory C-BP device over the 24 h. Materials and methods: Eighty-four consecutive patients were included in the study. BP was measured simultaneously by the CL-BP device and by a C-BP device over the 24 h. Calculations included 24 h mean systolic (S) BP, the mean diastolic (D) BP and the heart rate (HR). Correlations between the CL-BP and C-BP measurements were sought using Pearson’s correlation coefficients and Bland-Altman plots. Results: Using the C-BP device, the 24 h SBP value for the cohort was 125.4 ± 10.9 mmHg (mean ± SD); the corresponding DBP value being 75 ± 8.3 mmHg. Mean SBP/DBP were higher with the CL-BP device, i.e. 131.1 ± 15.9/80.2 ± 9.7 mmHg . The correlation coefficients between the two sets of values were significant (SBP: r = 0.58, DBP: r = 0.65). Better correlations for SBP and DBP were found 1) in patients with BMI > 25 (SBP: r = 0.65, DBP: r = 0.70) compared to those with BMI <25 and 2) in males compared to females (SBP: r = 0.71, DBP: r = 0.77). Conclusions: In our patients a CL-BP device estimated 24 h mean SBP and DBP differently from the classical oscillometric device, with a moderate correlation. CL-BP measurements were most accurate on male and overweight subjects.
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