Histopathological Growth Pattern in Colorectal Liver Metastasis and The Tumor Immune Microenvironment

Almost half of all patients with colorectal cancer present with or eventually develop metastasis, most frequently in the liver. Understanding the histopathological growth patterns and tumor immune microenvironment of colorectal liver metastases may help determine treatment strategies and assess prognosis. A literature search was conducted to gather information on cancer biology, histopathological growth patterns, and the tumor immune microenvironment in colorectal liver metastases, including their mechanisms and their impact on clinical outcomes. A first consensus on histopathological growth patterns emerged in 2017, identifying five growth patterns. Later studies found benefits from a two-tier system, desmoplastic and non-desmoplastic, incorporated into the updated 2022 consensus. Furthermore, the tumor immune microenvironment shows additional characteristic features with relevance to cancer biology. This includes density of T-cells (CD8+), expression of claudin-2, presence of vessel co-option versus angiogenesis, as well as several other factors. The relation between histopathological growth patterns and the tumor immune microenvironment delineates distinct subtypes of cancer biology. The distinct subtypes are found to correlate with risk of metastasis or relapse, and hence to clinical outcome and long-term survival in each patient. In order to optimize personalized and precision therapy for patients with colorectal liver metastases, further investigation into the mechanisms of cancer biology and their translational aspects to novel treatment targets is warranted.publishedVersio

Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery

Background The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis. Analysis and Results Currently, there are no designated diagnostic or screening tests for pancreatic cancer in clinical use. Thus, identifying risk groups, preclinical risk factors or surveillance strategies to facilitate early detection is a target for ongoing research. Hereditary genetic syndromes are a obvious, but small group at risk, and warrants close surveillance as suggested by society guidelines. Screening for pancreatic cancer in asymptomatic individuals is currently associated with the risk of false positive tests and, thus, risk of harms that outweigh benefits. The promise of cancer biomarkers and use of ‘omics’ technology (genomic, transcriptomics, metabolomics etc.) has yet to see a clinical breakthrough. Several proposed biomarker studies for early cancer detection lack external validation or, when externally validated, have shown considerably lower accuracy than in the original data. Biopsies or tissues are often taken at the time of diagnosis in research studies, hence invalidating the value of a time-dependent lag of the biomarker to detect a pre-clinical, asymptomatic yet operable cancer. New technologies will be essential for early diagnosis, with emerging data from image-based radiomics approaches, artificial intelligence and machine learning suggesting avenues for improved detection. Conclusions Early detection may come from analytics of various body fluids (eg ‘liquid biopsies’ from blood or urine). In this review we present some the technological platforms that are explored for their ability to detect pancreatic cancer, some of which may eventually change the prospects and outcomes of patients with pancreatic cancer.publishedVersio

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Programmed death ligand-1 (PD-L1) clone 22C3 expression in resected colorectal cancer as companion diagnostics for immune checkpoint inhibitor therapy: A comparison study and inter-rater agreement evaluation across proposed cut-offs and predictive (TPS, CPS and IC) scores

Background: Expression of programmed death ligand-1 (PD-L1) guides the use of immune checkpoint inhibitors (ICI) in several cancers. In colorectal cancer (CRC), ICI are only approved for metastatic CRC, while several studies suggest high efficacy even in operable CRC. The aim of this study was to investigate the inter-rater agreement of PD-L1 as a companion diagnostic marker. Methods: Specimens from resected stage I-III CRC (n = 166 tumors) were stained with PD-L1 22C3 clone. PD-L1 expression was scored by two pathologists as tumor proportion score (TPS), combined positive score (CPS) and immune cell score (IC). Inter-rater agreement was tested using three different agreement coefficients. Results: Raw scores of the two pathologists had ‘good’ to ‘excellent’ correlation. Spearman's rho for TPS=0.917 (95 %CI 0.839–0.995), for CPS=0.776 (95 %CI 0.726–0.826) and IC=0.818 (95 %CI 0.761–0.875). For TPS, kappa (κ)-agreements for both the ≥1 % and ≥10 % cutoffs had excellent correlation. For CPS the ≥1 % and ≥10 % cutoffs demonstrated κ=0.32 (95 %CI 0.12–0.51) and κ=0.36 (95 %CI 0.25–0.48) respectively. Cutoffs for IC showed κ=0.53 (95 %CI 0.18–0.79) for the ≥1 % cutoff, and κ=0.61 (95 %CI 0.48–0.73) for the ≥10 % cutoff. Gwet's agreement coefficient (AC1) showed higher agreement coefficients than κ-values for most, but not all cut-offs. Conclusion: Agreement for PD-L1 was good to excellent for raw scores. Agreement variation across several criteria and cut-offs suggests the need for more robust criteria for PD-L1 as a companion diagnostic marker

Developing Sustainable Food Systems in Europe: National Policies and Stakeholder Perspectives in a Four-Country Analysis

To address climate change, health, and food-related challenges at the international and regional level, policy makers and researchers are starting to acknowledge the importance of building and developing sustainable food systems (SFSs). This study aims to discuss the drivers of, barriers to, and policy recommendations for developing sustainable food systems in four European countries (Germany, Italy, Norway, and Romania). We used critical frame analysis to investigate national policy documents on sustainable food systems and conducted in-depth interviews with various national stakeholders representing policy makers, agrifood businesses, and civil society. The novelty of this research lies in comparing national policy approaches and stakeholders' opinions on SFS development in a multi-country analysis. These European countries have different conditions in terms of geography, socioeconomic situation, environmental performance, and sustainability orientation. Several cross-cultural differences and gaps in the existing national policies for sustainable food systems were identified, and solutions that help overcome these issues have been suggested. The first step in developing SFS should focus on interdisciplinary and trans-sectorial policy integration combined with increasing stakeholder collaboration across all sectors of the economy. We also recommend more active involvement of consumers in the food system, developing information-sharing networks, and increasing collaborations within the food supply chains

Developing Sustainable Food Systems in Europe: National Policies and Stakeholder Perspectives in a Four-Country Analysis

To address climate change, health, and food-related challenges at the international and regional level, policy makers and researchers are starting to acknowledge the importance of building and developing sustainable food systems (SFSs). This study aims to discuss the drivers of, barriers to, and policy recommendations for developing sustainable food systems in four European countries (Germany, Italy, Norway, and Romania). We used critical frame analysis to investigate national policy documents on sustainable food systems and conducted in-depth interviews with various national stakeholders representing policy makers, agrifood businesses, and civil society. The novelty of this research lies in comparing national policy approaches and stakeholders’ opinions on SFS development in a multi-country analysis. These European countries have different conditions in terms of geography, socioeconomic situation, environmental performance, and sustainability orientation. Several cross-cultural differences and gaps in the existing national policies for sustainable food systems were identified, and solutions that help overcome these issues have been suggested. The first step in developing SFS should focus on interdisciplinary and trans-sectorial policy integration combined with increasing stakeholder collaboration across all sectors of the economy. We also recommend more active involvement of consumers in the food system, developing information-sharing networks, and increasing collaborations within the food supply chains

Exploring the Road to Agricultural Sustainability by Assessing the EU Debt Influencing Factors

The importance of agricultural financing in ensuring food security and safety, jobs, poverty reduction, economic growth and more recently, climate change mitigation, natural resource conservation and sustainable development imposes periodic analysis of the factors which might influence the farmers’ financial situation, in order to improve it. One way of assessing this is to analyze the agricultural debt. In this context, based on previous models, the paper aims to assess the impact of specific factors on the agricultural debt level in the European Union during 2008–2015, as these should be considered in future common agriculture policies as well as in achieving sustainable agriculture. The research was conducted based on econometric techniques, by applying panel models in the Eviews 7.0 software-64 bit version. More than 20 variables were considered in the analysis. Some of the findings suggest that an increase in subsidies as well as the share of cash flow in the total existing capital would determine considerable reductions of the total debt. Decoupled subsidies seem to have a higher impact than coupled subsidies on short term debt, while its value is between the one found for coupled subsidies in the case of long term debt. Large farms/companies, to which decoupled payments are granted, have higher debts on long run and on total debt. The same units, to which coupled subsidies were granted, have smaller short-term debt. In contrast, the increases of labor costs, fixed costs, and crop/livestock costs lead to an increase in the total debt, since the farms require additional financial resources to cover the expanded costs. Also, the results suggest that short-term debts are mainly formed of long-term loans that reached maturity. In this case, the authors support the idea of differentiated financing programs for the agricultural activities because of their peculiarities and reinforced by the need to turn the intensive agriculture into a sustainable and plentiful one