Transparency in Negotiation of European Union With Big Pharma on COVID-19 Vaccines

Immunization through vaccination represents one of the most cost-effective public health interventions and the main tool for primary prevention of communicable diseases. Vaccination programs and vaccine prices, however, vary considerably among and within countries in the European Union (EU), because of the differences in the way healthcare systems are organized at the national or regional levels. These differences may lead to a new threat represented by the so-called “vaccine nationalism” that keep negotiations with the pharmaceutical industry behind the closed doors of each single nation, thus undermining global efforts to ensure fair access to vaccines for everyone (1). The severity of the recent COVID-19 pandemic is urging a major change in our capabilities to respond in the most appropriate and coordinated manner to the emergency situation. Transparency about the different roles of all stakeholders, either public or private, of vaccine manufacturers, and of health authorities and, most importantly, transparency in negotiations regarding vaccine price, could help avoid misconceptions, thus strengthening the collaboration required to protect against the pandemic

Sparse bayesian imaging of solar flares

We consider imaging of solar flares from NASA Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) data as a parametric imaging problem, where flares are represented as a finite collection of geometric shapes. We set up a Bayesian model in which the number of objects forming the image is a priori unknown, as well as their shapes. We use a sequential Monte Carlo algorithm to explore the corresponding posterior distribution. We apply the method to synthetic and experimental data, largely known in the RHESSI community. The method reconstructs improved images of solar flares, with the additional advantage of providing uncertainty quantification of the estimated parameters

Investigation of VOCs associated with different characteristics of breast cancer cells

The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization

Analysis of adenomatous polyposis coli gene in thyroid tumours.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma

Age is not the only risk factor in COVID-19: the role of comorbidities and of long staying in residential care homes

Background: The actual SARS-CoV-2 outbreak caused a highly transmissible disease with a tremendous impact on elderly people. So far, few studies focused on very elderly patients (over 80 years old). In this study we examined the clinical presentation and the outcome of the disease in this group of patients, admitted to our Hospital in Rome. Methods: This is a single-center, retrospective study performed in the Sant’Andrea University Hospital of Rome. We included patients older than 65 years of age with a diagnosis of COVID-19, from March 2020 to May 2020, divided in two groups according to their age (Elderly: 65–80 years old; Very Elderly > 80 years old). Data extracted from the each patient record included age, sex, comorbidities, symptoms at onset, the Pneumonia Severity Index (PSI), the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) (P/F) on admission, laboratory tests, radiological findings on computer tomography (CT), length of hospital stay (LOS), mortality rate and the viral shedding. The differences between the two groups were analyzed by the Fisher’s exact test or the Wilcoxon signed-rank test for categorical variables and the Mann-Whitney U test for continuous variables. To assess significance among multiple groups of factors, we used the Bonferroni correction. The survival time was estimated by Kaplan-Meier method and Log Rank Test. Univariate and Multivariate logistic regression were performed to estimate associations between age, comorbidities, provenance from long-stay residential care homes (LSRCH) s and clinical outcomes. Results: We found that Very Elderly patients had an increased mortality rate, also due to the frequent occurrence of multiple comorbidities. Moreover, we found that patients coming from LSRCHs appeared to be highly susceptible and vulnerable to develop severe manifestations of the disease. Conclusion: We demonstrate that there were considerable differences between Elderly and Very Elderly patients in terms of inflammatory activity, severity of disease, adverse clinical outcomes. To establish a correct risk stratification, comorbidities and information about provenience from LSRCHs should be considered

Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies.METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC).RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3.CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified

Isomeric Decay of \u3csup\u3e208\u3c/sup\u3eRa

Low-energy excited states of 208Ra were investigated using the 182W(30Si, 4n) reaction at the Wright Nuclear Structure Laboratory of Yale University. Fusion evaporation recoils were selected using the gas-filled spectrometer SASSYER. Delayed γ rays, following isomeric decays, were detected at the focal plane of SASSYER with a small array of three clover Ge detectors. Transitions following a proposed J π = 8+ isomer were observed, and the half-life was measured

Isomers and Seniority in the Trans-Pb Nuclei

Low-energy excited states of 210Ra and 208Ra were investigated at the Wright Nuclear Structure Laboratory of Yale University. Fusion evaporation recoils were selected using the gas-filled spectrometer, SASSYER. Delayed γ -rays, following isomeric decays, were detected at the focal plane of SASSYER with a small array of HPGe detectors. Transitions following the proposed J π = 8+ isomers were observed, and the half-lives measured. The experiments are discussed and results compared to expectations from the seniority scheme

Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) represents the most common cause of hypothyroidism and nonendemic goiter, but its clinical and pathological heterogeneity opens the question if this disease should be more properly considered as a spectrum of different thyroid conditions rather than as a single nosological entity. In this study, we analysed 133 cases of HT for the expression of galectin-3, a lectin molecule involved in malignant transformation, apoptosis and cell cycle control. An unexpected expression of galectin-3 was demonstrated in a subset of HT together with the presence of HBME-1, c-met and cyclin-D1 that are also involved in malignant transformation and deregulated cell growth. Furthermore, a loss of allelic heterozygosity in a specific cancer-related chromosomal region was demonstrated in some HT harbouring galectin-3-positive follicular cells, by using laser capture microdissection. On the basis of the morphological and molecular findings we identified four subsets of HT: (a) HT with classic features of chronic autoimmune thyroiditis; (b) HT associated to hyperplastic/adenomatous lesions; (c) HT harbouring thyroid cancer precursors; (d) HT associated to unequivocal thyroid microcarcinomas. Our findings provide a well-substantiated morphological and molecular demonstration that HT may include a spectrum of different thyroid conditions ranging from chronic autoimmune thyroiditis to thyroiditis triggered by specific immune-response to cancer-related antigens

The Loss of the p53 Activator HIPK2 Is Responsible for Galectin-3 Overexpression in Well Differentiated Thyroid Carcinomas

Background: Galectin-3 (Gal-3) is an anti-apoptotic molecule involved in thyroid cells transformation. It is specifically overexpressed in thyroid tumour cells and is currently used as a preoperative diagnostic marker of thyroid malignancy. Gal-3 expression is downregulated by wt-p53 at the transcriptional level. In well-differentiated thyroid carcinomas (WDTCs) there is an unexplained paradoxical concomitant expression of Gal-3 and wt-p53. HIPK2 is a co-regulator of different transcription factors, and modulates basic cellular processes mainly through the activation of wt-p53. Since we demonstrated that HIPK2 is involved in p53-mediated Gal-3 downregulation, we asked whether HIPK2 deficiency might be responsible for such paradoxical Gal-3 overexpression in WDTC. Methodology/Principal Findings: We analyzed HIPK2 protein and mRNA levels, as well as loss of heterozygosity (LOH) at the HIPK2 locus (7q32-34), in thyroid tissue samples. HIPK2 protein levels were high in all follicular hyperplasias (FHs) analyzed. Conversely, HIPK2 was undetectable in 91.7% of papillary thyroid carcinomas (PTCs) and in 60.0% of follicular thyroid carcinomas (FTCs). HIPK2 mRNA levels were upregulated in FH compared to normal thyroid tissue (NTT), while PTC showed mean HIPK2 mRNA levels lower than FH and, in 61.5% of cases, also lower than NTT. We found LOH at HIPK-2 gene locus in 37.5% of PTCs, 14.3% of FTCs and 18.2% of follicular adenomas. To causally link these data with Gal-3 upregulation, we performed in vitro experiments, using the PTC-derived K1 cells, in which HIPK2 expression was manipulated by RNA interference (RNAi) or plasmid-mediated overexpression. HIPK2 RNAi was associated with Gal-3 upregulation, while HIPK2 overexpression with Gal-3 downregulation. Conclusions/Significance: Our results indicate that HIPK2 expression and function are impaired in WDTCs, in particular in PTCs, and that this event explains Gal-3 overexpression typically observed in these types of tumours. Therefore, HIPK2 can be considered as a new tumour suppressor gene for thyroid cancers