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This document is an update of the analysis and systematic review of best practices, technologies and applications presented in D2.2 of Ageing@Work.The objective of this deliverable is once the final solution of the Ageing@Work project is already designed and first version of the solutions implemented ready to be deployed and evaluated, discover new solutions aimed to improve the second version of the Ageing@Work system, and have an updated pull of information to solve the possible issues during the piloting phase. Ageing@Work has received funding from the EU Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 826299

In December 2018, Diabetes and Diabetologia began requiring authors of papers reporting data obtained from studies on human islets to report critical characteristics of the human islets used for research. The islet community was asked to provide feedback on it. Here is the contribution by the European Consortium for Islet Transplantation.

This dialogue with Luca Mercalli, researcher and science communicator of environmental issues, focuses on the link between climate change and migration, with a particular reference to what is currently happening here and there in Italian mountains. It is a sort of ‘upwelling’ towards mountain areas whose protagonists (new mountaineers) try to fulfil not only an economic but also a life project. Mercalli explains the reasons of this movement towards the mountains which, in the next future, will become an increasingly central issue in territorial policies, telling his personal experience and choice to live in the upper Susa valley, in the borough of Vazon (Oulx). A complex challenge, this, between struggles and the great beauty expressed in that place. Attention and regard to the place accompany his project both in re-functionalizing and in building technique choices. A sort of ship’s log that helps reflect on the urgent programmes and policies for the re-activation of mountain territories., Scienze del Territorio, Vol. 9 (2021): La nuova centralità della montagna / The new centrality of mountains

AimThe aim of the current study was to compare clinical characteristics, laboratory findings and major outcomes of patients hospitalized for COVID-19 pneumonia with COVID-associated hyperglycaemia or preexisting diabetes.MethodsA cohort of 176 adult patients with a diagnosis of pre-existing diabetes (n=112) or COVID-associated hyperglycaemia (n=55) was studied. Clinical outcomes and laboratory findings were analysed according to the presence of the two conditions. The time to viral clearance was assessed during the follow-up after hospital discharge.ResultPatients with COVID-associated hyperglycaemia had lower BMI, significantly less comorbidities and higher levels of inflammatory markers and indicators of multi-organ injury than those with preexisting diabetes. No differences between preexisting diabetes and COVID-associated hyperglycaemia were evident for symptoms at admission, humoral response against SARS-CoV-2 or autoantibodies to glutamic acid decarboxylase or interferon alpha-4. COVID-associated hyperglycaemia was independently associated with the risk of adverse clinical outcome defined as ICU admission or death (HR 2.11, 95% CI 1.34-3.31; p=0.001), even after adjustment for age, sex and other selected variables associated with COVID-19 severity. Furthermore, we documented a negative association (HR 0.661, 95% CI 0.43-1.02; p=0.063) between COVID-associated hyperglycaemia and the time to swab negativization.ConclusionsThe recognition of hyperglycaemia as a specific clinical entity associated with COVID-19 pneumonia is relevant for early and appropriate patient management and close monitoring for the progression of disease severity.

Alpine glaciers respond to climate imbalance by adjusting their mass and length. In turn, these changes modify the glacial and periglacial environment, leading to increased supraglacial debris cover, the development of glacial lakes and glacier fragmentation. In this research, we investigated the evolution of Lys Glacier (Monte Rosa Group), by studying length, area and volume changes, and evolution of its supraglacial debris cover and proglacial lakes by means of historical sources and high-resolution aerial and satellite orthophotos. Lys Glacier retreated almost continuously, by nearly 2 km, from its maximum Little Ice Age position. More recently, the glacier lost 11.91% of its area between 1975 and 2014 and underwent fragmentation in 2009. Over the same period, glacier fragmentation and tongue stagnation affected the formation and rapid growth of a series of ice-contact lakes and led to a non-linear debris cover evolution. The glacier was also subjected to strong volume losses, with more than 135 m thinning on the ablation tongue from 1991 to 2014. Analysis of the meteorological records (1927–present) from the closest weather station reveals a considerable increase in average annual temperatures by more than 1°C from the mean of 1971–1989 to the mean of 1990–2017.

Background Despite advances in treatments, 30% to 50% of stage III-IV head and neck squamous cell carcinoma (HNSCC) patients relapse within 2 years after treatment. The Big Data to Decide (BD2Decide) project aimed to build a database for prognostic prediction modeling. Methods Stage III-IV HNSCC patients with locoregionally advanced HNSCC treated with curative intent (1537) were included. Whole transcriptomics and radiomics analyses were performed using pretreatment tumor samples and computed tomography/magnetic resonance imaging scans, respectively. Results The entire cohort was composed of 71% male (1097)and 29% female (440): oral cavity (429, 28%), oropharynx (624, 41%), larynx (314, 20%), and hypopharynx (170, 11%); median follow-up 50.5 months. Transcriptomics and imaging data were available for 1284 (83%) and 1239 (80%) cases, respectively; 1047 (68%) patients shared both. Conclusions This annotated database represents the HNSCC largest available repository and will enable to develop/validate a decision support system integrating multiscale data to explore through classical and machine learning models their prognostic role.

The loss of parenchyma after pancreatectomy causes an extreme disruption of glucose homeostasis known as “pancreatogenic diabetes” which is characterized by disabling episodes of hyperglycemia or hypoglycemia, increased morbidity and mortality, and target organ damage. The number of subjects undergoing pancreatic surgery is increasing, owing to early diagnosis of premalignant lesions and to the referral of patients affected by surgical pancreatic diseases to high-volume institutions. Therefore, a growing number of pancreatectomized patients with long life expectancy is exposed to the risk of pancreatogenic diabetes, with a significant impact on quality and duration of life. Islet autotransplantation (IAT) could offer a valuable option to avoid “pancreatogenic diabetes.” In fact, the most successful islet transplants have been performed in no autoimmune diabetes patients, in an autologous setting, in conjunction with total or near total pancreatectomy for the treatment of pancreatic or hepatobiliary conditions. Here we discuss the feasibility, efficiency, and safety of IAT for the prevention of surgical diabetes after extensive or total pancreatic resection for pancreas disease other than chronic pancreatitis.

Curing type 1 diabetes means replacing the lost insulin secretion with a perpetual, autonomous, and self-regulating source of insulin delivery able to correct all the metabolic abnormalities and prevent the long-term chronic complications of the disease. In Milan, substantial experience in islet transplantation and beta-cell replacement has been gained and maintained during the last three decades, thereby achieving a leading position in the production of human islets for transplantation and its establishment as one of the most experienced centers in the world with more than 370 islet infusions performed and high-level scientific production. During this long period the field of islet transplantation has evolved significantly from the breakthrough of the first cases in early 1990s, since significant advances in islet isolation and engraftment, together with improved immunosuppressive strategies, have been reported. A major effort is now being focused on a special multidisciplinary and integrated project aiming at bringing islet transplantation and beta-cell replacement to the level of a successful clinical routine procedure.

This document presents the analysis and systematic review of 14 best practices, 15 technologies and 26 different applications and tools that are currently used or can be used to assist workers in maintaining their workability and well-being. Special emphasis has been placed on older workers, who suffer a greater risk of hindering their work ability and well-being, mainly due to the effects of ageing. Ageing@Work has received funding from the EU Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 826299 &nbsp

Historical weather data represent an extremely precious resource for agro-meteorology for studying evolutionary dynamics and for predictive purposes, to address agronomical and management choices, that have economic, social and environmental effect. The study of climatic variability and its consequences starts from the observation of variations over time and the identification of the causes, on the basis of historical series of meteorological observations. The availability of long-lasting, complete and accurate datasets is a fundamental requirement to predict and react to climate variability. Inter-annual climate changes deeply affect grapevine productive cycle determining direct impact on the onset and duration of phenological stages and, ultimately, on the grape harvest and yield. Indeed, climate variables, such as air temperature and precipitation, affect evapotranspiration rates, plant water requirements, and also the vine physiology. In this respect, the observed increase in the number of warm days poses a threat to grape quality as it creates a situation of imbalance at maturity, with respect to sugar content, acidity and phenolic and aromatic ripeness.A study was conducted to investigate the relationships between climate variables and harvest onset dates to assess the responses of grapevine under a global warming scenario. The study was carried out in the “Monferrato” area, a rainfed hillslope vine-growing area of NW Italy. In particular, the onset dates of harvest of different local wine grape varieties grown in the Vezzolano Experimental Farm (CNR-IMAMOTER) and in surrounding vineyards (affiliated to the Terre dei Santi Cellars) were recorded from 1962 to 2019 and then related to historical series of climate data by means of regression analysis. The linear regression was performed based on the averages of maximum and minimum daily temperatures and sum of precipitation (1962–2019) calculated for growing and ripening season, together with a bioclimatic heat index for vineyards, the Huglin index. The climate data were obtained from two data series collected in the Experimental farm by a mechanical weather station (1962-2002) and a second series recorded (2002-2019) by an electro-mechanical station included in Piedmont Regional Agro-meteorological Network. Finally, a third long-term continuous series covering the period from 1962 to 2019, provided by Italian Meteorological Society was considered in the analysis.The results of the study highlighted that inter-annual climate variability, with a general positive trend of temperature, significantly affects the ripening of grapes with a progressive anticipation of the harvest onset dates. In particular, all the considered variables excepted precipitation, resulted negatively correlated with the harvest onset date reaching a high level of significance (up to P< 0.001). Best results have been obtained for maximum temperature and Huglin index, especially by using the most complete dataset. The change ratios obtained using datasets including last 15 years were greater (in absolute terms) than results limited to the period 1962-2002, and also correlations have greater level of significance. The results indicated clearly the relationships between the temperature trend and the gradual anticipation of harvest and the importance of having long and continuous historical weather data series available.

In the last years, we have investigated the click-chemical space covered by molecules containing the triazole ring and generated a database of 1,2,3-triazoles called ZINClick, starting from literature-reported alkynes and azides synthesizable in no more than three synthetic steps from commercially available products. This combinatorial database contains millions of 1,4-disubstituted 1,2,3-triazoles that are easily synthesizable. The library is regularly updated and can be freely downloaded from http://www.ZINClick.org . In this communication, the new implementation of ZINClick will be discussed as well as our new strategy for clustering the chemical space covered by 1,4-disubstituted 1,2,3-triazoles around their availability: from direct purchase to different degrees of synthetic feasibility of the compounds.

Background Patients with severe pneumonia often develop septic shock. IgM-enriched immunoglobulins have been proposed as a potential adjuvant therapy for septic shock. While in vitro data are available on the possible mechanisms of action of IgM-enriched immunoglobulins, the results of the in vivo experimental studies are non-univocal and, overall, unconvincing. We designed this double blinded randomized controlled study to test whether IgM-enriched immunoglobulins administered as rescue treatment in a pneumonia model developing shock, could either limit lung damage and/or contain systemic inflammatory response. Methods Thirty-eight Sprague Dawley rats were ventilated with injurious ventilation for 30 min to prime the lung. The rats were subsequently randomized to received intratracheal instillation of either lipopolysaccharide (LPS) (12 mg/kg) or placebo followed by 3.5 h of protective mechanical ventilation. IgM-enriched immunoglobulins at 25 mg/h (0.5 mL/h) or saline were intravenously administered in the last hour of mechanical ventilation. During the experiment, gas exchange and hemodynamic measurements were recorded. Thereafter, the animals were sacrificed, and blood and organs were stored for cytokines measurements. Results Despite similar lung and hemodynamic findings, the administration of IgM-enriched immunoglobulins compared to placebo significantly modulates the inflammatory response by increasing IL-10 levels in the bloodstream and by decreasing TNF-α in bronchoalveolar lavage (BAL) fluid. Furthermore, in vitro data suggest that IgM-enriched immunoglobulins induce monocytes production of IL-10 after LPS stimulation. Conclusions In an in vivo model of pneumonia developing shock, IgM-enriched immunoglobulins administered as rescue treatment enhance the anti-inflammatory response by increasing blood levels of IL-10 and reducing TNF-α in BAL fluid.

A convergent and efficient two-step synthesis of pharmaceutically relevant 1-arylindazole-3-carboxamides is reported. These molecules have been obtained in good to excellent yields (up to 98%) starting from a strategic reaction between isocyanides, 2-iodo-N-arylbenzohydrazonoyl chlorides and 2-hydroxymethylbenzoic acid followed by a chemoselective Buchwald–Hartwig intramolecular cyclization. This novel strategy provides an additional indazole synthesis to those already reported in literature both in the type of substrate as well as the substitution pattern obtainable in the products. Furthermore benzylisocyanide is herein reported for the first time as a convertible isocyanide providing an expeditious access to N-arylindazole-3-carbonitriles.