A multi-approach software library for estimating crop suitability to environment

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Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification

Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification

Invariant Natural Killer T (iNKT) cells in HAART-treated, HIV-positive patients with bone and cardiovascular impairment

Background: Invariant Natural Killer T (iNKT) cells represent a determinant in the course of infections and diseases, however, their role in the pathogenesis of non-infectious co-morbidities in HIV-positive patients is unknown. Methods: Flow cytometry was used to investigate iNKT cell frequency, phenotype and function in HIV-infected patients on HAART with bone and/or cardiovascular disorders and in HIV-positive controls free from co-morbidities. Results: iNKT cells from subjects with bone and cardiovascular impairment expressed high levels of CD161 and predominantly secreted TNF. iNKT cells from individuals with bone disease alone did not show any distinctive phenotypical or functional characteristics. The functional capacity of iNKT cells in patients with cardiovascular disorder was impaired with no cytokine release upon stimulation. Conclusion: iNKT cells may have a role in non-infectious co-morbidities in treated HIV disease, possibly through the exacerbation of inflammation. Further studies are needed to investigate iNKT cells in the pathogenesis of non-communicable disorders in HIV infection

Monitoring tumor growth rate to predict immune checkpoint inhibitors' treatment outcome in advanced NSCLC

Introduction: Radiological response assessment to immune checkpoint inhibitor is challenging due to atypical pattern of response and commonly used RECIST 1.1 criteria do not take into account the kinetics of tumor behavior. Our study aimed at evaluating the tumor growth rate (TGR) in addition to RECIST 1.1 criteria to assess the benefit of immune checkpoint inhibitors (ICIs). Methods: Tumor real volume was calculated with a dedicated computed tomography (CT) software that semi-automatically assess tumor volume. Target lesions were identified according to RECIST 1.1. For each patient, we had 3 measurement of tumor volume. CT-1 was performed 8-12 weeks before ICI start, the CT at baseline for ICI was CT0, while CT + 1 was the first assessment after ICI. We calculated the percentage increase in tumor volume before (TGR1) and after immunotherapy (TGR2). Finally, we compared TGR1 and TGR2. If no progressive disease (PD), the group was disease control (DC). If PD but TGR2 < TGR1, it was called LvPD and if TGR2 > TGR1, HvPD. Results: A total of 61 patients who received ICIs and 33 treated with chemotherapy (ChT) were included. In ICI group, 18 patients were HvPD, 22 LvPD, 21 DC. Median OS was 4.4 months (95% CI: 2.0-6.8, reference) for HvPD, 7.1 months (95% CI 5.4-8.8) for LvPD, p = 0.018, and 20.9 months (95% CI: 12.5-29.3) for DC, p < 0.001. In ChT group, 7 were categorized as HvPD, 17 as LvPD and 9 as DC. No difference in OS was observed in the ChT group (p = 0.786) Conclusion: In the presence of PD, a decrease in TGR may result in a clinical benefit in patients treated with ICI but not with chemotherapy. Monitoring TGR changes after ICIs administration can help physician in deciding to treat beyond PD

Building an XML document warehouse

International audienceData Warehouses and OLAP (On Line Analytical Processing) technologies are dedicated to analyzing structured data issued from organizations' OLTP (On Line Transaction Processing) systems. Furthermore, in order to enhance their decision support systems, these organizations need to explore XML (eXtensible Markup Language) documents as an additional and important source of unstructured data. In this context, this paper addresses the warehousing of document-centric XML documents. More specifically, we propose a two-method approach to build Document Warehouse conceptual schemas. The first method is for the unification of XML document structures; it aims to elaborate a global and generic view for a set of XML documents belonging to the same domain. The second method is for designing multidimensional galaxy schemas for Document Warehouses

Impact of clonal hematopoiesis of indeterminate potential on hepatocellular carcinoma in individuals with steatotic liver disease

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) is a global epidemic and is the most rapidly rising cause of hepatocellular carcinoma (HCC). Clonal hematopoiesis of indeterminate potential (CHIP) contributes to neoplastic and cardiometabolic disorders and is considered a harbinger of tissue inflammation. CHIP was recently associated with increased risk of liver disease. The aim of this study was to examine whether CHIP is associated with HCC development in patients with SLD. Methods: We considered individuals with MASLD-HCC (n=208) and controls with (n=414) and without (n=259) advanced fibrosis who underwent whole exome sequencing. CHIP was diagnosed when >= 2 variant callers identified a known myeloid mutation with VAF >= 2%. Results: CHIP was observed in 116 participants (13.1%), most frequently in DNMT3A, TET2, TP53 and ASXL1, and correlated with age (p<0.0001) and advanced liver fibrosis (p=0.001). Higher AST levels predicted non-DNMT3A-CHIP, in particular with variant allele frequency (VAF)>= 10% (OR 1.14, 1.03-1.28 and OR 1.30, 1.12-1.49, respectively, p<0.05). After adjustment for sex, diabetes and a polygenic risk score of inherited MASLD predisposition CHIP was associated with cirrhosis (2.00, 1.30-3.15, p=0.02), and with HCC even after further adjustment for cirrhosis (OR 1.81, 1.11-2.00, 1.30-3.15, p=0.002). Despite the strong collinearity among aging and development of CHIP and HCC, non-DNTM3A-CHIP and TET2 lesions remained associated with HCC after full correction for clinical/genetics covariates and age (OR 2.45, 1.35-4.53; OR 4.8, 1.60-17.0, p=0.02). Conclusions: We observed an independent association between CHIP, particularly related to non-DNTM3A and TET2 genetic lesions, and MASLD-HCC

Screening of Tanzanian medicinal plants for anti-Candida activity

BACKGROUND: Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents. METHODS: Sixty-three plant extracts, from 56 Tanzanian plant species obtained through the literature and interviews with traditional healers, were evaluated for anti-Candida activity. Aqueous methanolic extracts were screened for anti-Candida activity by bioautography agar overlay method, using a standard strain of Candida albicans (ATCC 90028). RESULTS: Twenty- seven (48%) out of the 56 plants were found to be active. Extracts of the root barks of Albizia anthelmintica and Balanites aegyptiaca, and roots of Plectranthus barbatus showed strong activity. CONCLUSION: The extracts that showed strong anti-Candida activity are worth of further investigation in order to isolate and identify the active compounds

Le competenze legislative in materia di "tutela della salute"

Il capitolo è dedicato al riparto delle competenze legislative tra Stato e regioni in materia di "tutela della salute". La riflessione tiene conto della principale giurisprudenza costituzionale intervenuta dal 2001 al 2012 in materia, evidenziando le interconnessione con altri ambiti materiali enumerati nell'art. 117 della Costituzione italiana. Particolare attenzione viene dedicata alla nuova conformazione della legislazione concorrente sulla tutela della salute ed ai problemi posti dalle finalità di contenimento della spesa sanitaria