Integrating CERIF Entities in a Multidisciplinary e-infrastructure for Environmental Research Data

AbstractThe paper proposes different solutions to integrate CERIF in the environmental dataset domain, based on the quality of semantic mapping as well as on the characteristics of the CERIF data model. A two-way crosswalk is described resulting in the identification of a core of corresponding metadata and a proposal of extensions of the CERIF model. Extensions of ISO concepts are also described to provide contextual research information in the domain of environmental research data. Finally, the crosswalk has been implemented in the GI-cat discovery broker framework. Successful tests demonstrated the possibility for CERIF information to be integrated in ISO compliant infrastructures and for INSPIRE information to be captured in CERIF

Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

Health-Related Quality of Life in Patients with CVID Under Different Schedules of Immunoglobulin Administration: Prospective Multicenter Study

We assessed the health-related quality of life (HRQoL) in CVID adults receiving different schedules of immunoglobulin replacement therapy (IgRT) by intravenous (IVIG), subcutaneous (SCIG), and facilitated (fSCIG) preparations. For these patients, IgRT schedule was chosen after a period focused on identifying the most suitable individual option

In Situ Aerobic Biostimulation of Groundwater at a National Priority Site in Italy

Sarroch plant (CA, Italy) is an industrial area listed in the Italian Priority List of polluted sites. Pollution in groundwater has been addressed thanks to the design of a remediation action based on the aerobic biodegradation of petroleum hydrocarbons (predominantly mono-aromatic and short-chain aliphatic hydrocarbons) promoted by the injection of oxygen-releasing compounds. The feasibility of biostimulation at the site was preliminary assessed by means of laboratory tests. The direct push injection of the product has been foreseen at 2800 points, distributed along multiple lines perpendicular to the groundwater flow direction, over a total length of approximately 8 km and a total area of 90 hectares. According to the pollutant concentration measured in the different zones of the site, a different number of injection campaigns and injection frequency has been scheduled (3 to 10 campaigns, every 5 to 12 months). The estimated cost for the bioremediation action is 23 million Euros. Compared to the previous project approved in 2010, including a seafront physical barrier and groundwater circulation wells – in situ well stripping, the in situ injection of the oxygen-releasing compounds is an improvement toward a quicker, more effective and sustainable remediation of groundwater at the site. In view of all this, in 2017 the public authorities approved the variant of the project

Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma

Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that all synthesized compounds are potent and subtype-selective inhibitors of PDK. Accordingly, molecular modeling studies revealed that a lot of ligands can be properly placed inside the ATP-binding site of PDK1. Interestingly, 2D and 3D cell studies revealed their ability to induce cancer cell death at low micromolar doses, being extremely effective against human pancreatic KRAS mutated cancer cells. Cellular mechanistic studies confirm their ability to hamper the PDK/PDH axis, thus leading to metabolic/redox cellular impairment, and to ultimately trigger apoptotic cancer cell death. Remarkably, preliminary in vivo studies performed on a highly aggressive and metastatic Kras-mutant solid tumor model confirm the ability of the most representative compound 5i to target the PDH/PDK axis in vivo and highlighted its equal efficacy and better tolerability profile with respect to those elicited by the reference FDA approved drugs, cisplatin and gemcitabine. Collectively, the data highlights the promising anticancer potential of these novel PDK-targeting derivatives toward obtaining clinical candidates for combatting highly aggressive KRAS-mutant pancreatic ductal adenocarcinomas

Biparametric prostate MRI: impact of a deep learning-based software and of quantitative ADC values on the inter-reader agreement of experienced and inexperienced readers

Objective To investigate the impact of an artificial intelligence (AI) software and quantitative ADC (qADC) on the inter-reader agreement, diagnostic performance, and reporting times of prostate biparametric MRI (bpMRI) for experienced and inexperienced readers. Materials and methods A total of 170 multiparametric MRI (mpMRI) of patients with suspicion of prostate cancer (PCa) were retrospectively reviewed by one experienced and one inexperienced reader three times, following a wash-out period. First, only the bpMRI sequences, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) sequences, and apparent diffusion coefficient (ADC) maps, were used. Then, bpMRI and quantitative ADC values were used. Lastly, bpMRI and the AI software were used. Inter-reader agreement between the two readers and between each reader and the mpMRI original reports was calculated. Detection rates and reporting times were calculated for each group. Results Inter-reader agreement with respect to mpMRI was moderate for bpMRI, Quantib, and qADC for both the inexperienced (weighted k of 0.42, 0.45, and 0.41, respectively) and the experienced radiologists (weighted k of 0.44, 0.46, and 0.42, respectively). Detection rate of PCa was similar between the inexperienced (0.24, 0.26, and 0.23) and the experienced reader (0.26, 0.27 and 0.27), for bpMRI, Quantib, and qADC, respectively. Reporting times were lower for Quantib (8.23, 7.11, and 9.87 min for the inexperienced reader and 5.62, 5.07, and 6.21 min for the experienced reader, for bpMRI, Quantib, and qADC, respectively). Conclusions AI and qADC did not have a significant impact on the diagnostic performance of both readers. The use of Quantib was associated with lower reporting times

Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs). The results showed that most of derivatives totally inhibit PDK1 and PDK4. Molecular docking analysis was executed to predict the possible binding mode of these derivatives using ligand-based homology modeling technique. Evaluation of the capability of new triazines to inhibit the cell growth in 2D and 3D KRAS-wild-type (BxPC-3) and KRAS-mutant (PSN-1) PDAC cell line, was carried out. The results showed the capacity of the new derivatives to reduce cell growth with a major selectivity against KRAS-mutant PDAC PSN-1 on both cell models. These data demonstrated that the new triazine derivatives target PDK1 enzymatic activity and exhibit cytotoxic effects on 2D and 3D PDAC cell models, thus encouraging further structure manipulation for analogs development against PDA

Standardization of body composition status in patients with advanced urothelial tumors: the role of a CT-based aI-powered software for the assessment of sarcopenia and patient outcome correlation

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes

The 31 Deg2^2 Release of the Stripe 82 X-ray Survey: The Point Source Catalog

We release the next installment of the Stripe 82 X-ray survey point-source catalog, which currently covers 31.3 deg$^2$ of the Sloan Digital Sky Survey (SDSS) Stripe 82 Legacy field. In total, 6181 unique X-ray sources are significantly detected with {\it XMM-Newton} ($>5\sigma$) and {\it Chandra} ($>4.5\sigma$). This catalog release includes data from {\it XMM-Newton} cycle AO 13, which approximately doubled the Stripe 82X survey area. The flux limits of the Stripe 82X survey are $8.7\times10^{-16}$ erg s$^{-1}$ cm$^{-2}$, $4.7\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$, and $2.1\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$ in the soft (0.5-2 keV), hard (2-10 keV), and full bands (0.5-10 keV), respectively, with approximate half-area survey flux limits of $5.4\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$, $2.9\times10^{-14}$ erg s$^{-1}$ cm$^{-2}$, and $1.7\times10^{-14}$ erg s$^{-1}$ cm$^{-2}$. We matched the X-ray source lists to available multi-wavelength catalogs, including updated matches to the previous release of the Stripe 82X survey; 88\% of the sample is matched to a multi-wavelength counterpart. Due to the wide area of Stripe 82X and rich ancillary multi-wavelength data, including coadded SDSS photometry, mid-infrared {\it WISE} coverage, near-infrared coverage from UKIDSS and VHS, ultraviolet coverage from {\it GALEX}, radio coverage from FIRST, and far-infrared coverage from {\it Herschel}, as well as existing $\sim$30\% optical spectroscopic completeness, we are beginning to uncover rare objects, such as obscured high-luminosity AGN at high-redshift. The Stripe 82X point source catalog is a valuable dataset for constraining how this population grows and evolves, as well as for studying how they interact with the galaxies in which they live.Comment: accepted for publication in ApJ; 23 pages (emulateapj