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In spite of major effectiveness, a residual risk after COVID-19 primary vaccination was identified, in particular, for vulnerable individuals of advanced age or with comorbidities. Less is known about the Omicron period in people protected by a booster dose. We aimed to identify the characteristics associated with severe COVID-19 during the Omicron period in a population that had received a booster dose in France and to compare differences with the previous periods of the pandemic. This study was carried out using the French national COVID-19 vaccination database (VAC-SI) coupled with the National Health Data System (SNDS). Individuals aged 12 years or over who received at least one booster dose were identified. Associations between socio-demographic and clinical characteristics and the risk of COVID-19 hospitalisation occurring at least 14 days after receiving a third dose of vaccine during the period of Omicron predominance, i.e., from 1 January 2022 to 10 November 2022, were assessed using Cox proportional hazard models adjusted for age, sex, time since booster dose and vaccination schedule. Analyses were performed overall and by sub-period of circulation of the strains BA.1, BA.2, and BA.4/BA.5, defined as periods where the main sub-variant accounted for more than 80 % of genotyped samples. In total, 35,640,387 individuals received a booster dose (mean follow-up of 291 days) and 73,989 were hospitalised for COVID-19 during the total period. Older age (aHR 20.5 95 % CI [19.6–21.5] for 90 years of age or older versus 45–54 years of age), being male (aHR 1.52 [1.50–1.55]), and social deprivation (aHR 1.33 [1.30–1.37] for the most deprived areas versus the least deprived) were associated with an increased risk of hospitalisation for COVID-19. Most of the chronic diseases considered were also positively associated with a residual risk, in particular, cystic fibrosis (aHR 9.83 [7.68–12.56]), active lung cancer (aHR 3.26 [3.06–3.47]), chronic dialysis (aHR 3.79 [3.49–4.11]), psychological and neurodegenerative diseases (more markedly than during the periods of circulation of the alpha and delta variants), and organ transplantation. The use of immunosuppressants was also associated with an increased risk (aHR 2.24 [2.14–2.35], including oral corticosteroids aHR (2.58 [2.50–2.67]). Despite an effective booster and a generally less virulent circulating variant, a residual risk of severe COVID-19 still exists in vulnerable populations, especially those with neurological disorders. [ABSTRACT FROM AUTHOR]

Large Granular Lymphocyte Leukemia (LGLL) is a rare chronic lymphoproliferative disorder characterized by the clonal expansion of Large Granular Lymphocytes (LGLs). Among LGLL, the 2016 WHO classification recognizes two different entities, i.e. T-LGLL and the provisional entity Chronic Lymphoproliferative disorder of NK cells (CLPD-NK). In both subtypes neutropenia represents the hallmark of the disease and is frequently regarded as the leading reason to start treatment. Leukemic LGLs are characterized by the up-regulation of several pro-survival signaling pathways, the most relevant being the JAK-STAT axis, whose constitutive activation is partly explained by somatic mutations in STAT3 and STAT5b. In addiction, in the last few years, a relationship between STAT3 mutations/activation and the development of neutropenia was found. Given that backbone treatment relying on immunosuppressive agents is generally unsatisfactory, novel agents targeting the JAK/STAT pathway can represent a turning point in LGLL treatment. [ABSTRACT FROM AUTHOR]

Large Granular Lymphocyte (LGL) Leukemia is a rare, heterogeneous even more that once thought, chronic lymphoproliferative disorder characterized by the clonal expansion of T- or NK-LGLs that requires appropriate immunophenotypic and molecular characterization. As in many other hematological conditions, genomic features are taking research efforts one step further and are also becoming instrumental in refining discrete subsets of LGL disorders. In particular, STAT3 and STAT5B mutations may be harbored in leukemic cells and their presence has been linked to diagnosis of LGL disorders. On clinical grounds, a correlation has been established in CD8+ T-LGLL patients between STAT3 mutations and clinical features, in particular neutropenia that favors the onset of severe infections. Revisiting biological aspects, clinical features as well as current and predictable emerging treatments of these disorders, we will herein discuss why appropriate dissection of different disease variants is needed to better manage patients with LGL disorders. [ABSTRACT FROM AUTHOR]

Accessibility to urban green spaces is essential for urban dwellers' health and well-being. For planning purposes different accessibility measures and indicators have been used. Some are only based on availability, others consider distance from residences, yet others rely on gravity-based methods that consider both supply and demand. Different indicators often provide diverse and sometimes contradictory results and many issues remain in developing a comprehensive measure of accessibility, and representativity problems remain in matching indices with reality. In this study different accessibility measures have been developed and applied to the urban parks of the city of Padova, in northeastern Italy. Effectiveness and reliability of ten indicators derived from these measures, in identifying needs, inadequacies and disparities in park access have been tested at the urban unit scale. The study confirmed that multiple indicators need to be used to provide a useful planning tool for the provision of adequate and equal opportunities for open space access to the citizens. The study has also shown which indicators can be replaced by each other without losing important information. • Measuring accessibility to green spaces with GIS is essential for urban planning. • Accessibility indicators provide diverse and sometimes contradictory results. • Correlation analysis can help avoiding replications and allowing for replaceability. • An integrated use of different types of accessibility indicators should be favored. [ABSTRACT FROM AUTHOR]

Summary Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo. [ABSTRACT FROM AUTHOR]

Background The possibility of predicting random future events before any sensory clues by using human physiology as a dependent variable has been supported by the meta-analysis of Moss-bridge et al. (2012) 1 and recent findings by Tressoldi et al. (2011 and 2013) 2,3 and Mossbridge et al. (2014) 4 defined this phenomenon predictive anticipatory activity (PAA). Aim of the study From a theoretical point of view, one interesting question is whether PAA is related to the effective, real future presentation of these stimuli or whether it is related only to the probability of their presentation. Methods This hypothesis was tested with four experiments, two using heart rate and two using pupil dilation as dependent variables. Results In all four experiments, both a neutral stimulus and a potentially threatening stimulus were predicted 7–10% above chance, independently from whether the predicted threatening stimulus was presented or not. Conclusion These findings are discussed with reference to the “grandfather paradox,” and some candidate explanations for this phenomena are presented. [ABSTRACT FROM AUTHOR]

Abstract: Modeling the environmental benefits of urban trees requires data which relate crown height, crown diameter, and leaf area to tree age or stem diameter (DBH). Growth prediction curves, that can be derived from the same data, can also be very useful for a better planning, design and development of the urban forest. However, very little information is available on the growth behavior of urban trees, and limited to few species and regional contexts. The aim of this study was to determine the relationships between tree age and various parameters of tree size in order to develop models to predict the growth of the most important species of an urban forest in northeastern Italy. The logarithmic regression model, proposed by and applied by , and other equations were tested in order to obtain the best fit for each species and parameter. All the models provided a better fit for the larger species (Tilia x vulgaris Hayne, Fraxinus angustifolia Vahl., Acer platanoides L.) than for the smaller ones (Prunus cerasifera “pissardi” (Carriere) L.H. Bailey and Lagerstroemia indica L.). The equations for predicting tree sizes and leaf area are presented and applied to compare size and growth 15 and 25 years after planting. According to the models A. platanoides attained the largest average annual DBH growth with values ranging from an average of 1.25cmyears−1 between 0 and 15 years after planting and 1.52cmyears−1 between 15 and 25 years after planting. L. indica showed the smaller DBH growth, ranging from 0.34cmyears−1 in the first period to 0.48cmyears−1 in the second period. 25 years after planting. A. platanoides L. is the tallest species and reaches the largest crown diameter, whith the largest average annual growth, followed by F. angustifolia and Tilia x vulgaris that show similar growth patterns. A comparison with predicted sizes in other studies confirms the need to extend the knowledge to the behavior of more species and more site specific conditions. [Copyright &y& Elsevier]

Abstract: The present landscape structure and function is the result of centuries of changes produced both by natural processes and human driving forces. For centuries many mountain and hillside areas have been the subject of deforestation to create space for agriculture and grazing, although the abandonment of traditional mountain agriculture has produced a natural forest recovery in many regions of the world. The physical changes imposed on the landscape by the development of secondary woodland have brought both positive and negative consequences, depending on the geographical and economic context and on the scale of the sites. Among the ecological problems caused by natural reforestation, one of great interest is the reduction of open spaces resulting in a loss of landscape heterogeneity and mosaic features. This review paper focused its attention on landscape metrics or indices that are frequently used to assess the structural characteristics of the landscape and to monitor changes in land use: mean patch size (MPS), connectivity (CONN), boundary length (BL) and the patch number (NP). Through the analysis of 52 selected papers and 53 case studies, we identified the main gaps in current knowledge, providing directions for further research. Most of the reviewed studies focused only on a portion of the spatial attributes that we were interested in and only 32 case studies reported accurate data both on forest expansion rate and time range analyzed in the study area. We conclude that the study of changes in all the spatial attributes considered within the same case study is a key to explain ecological consequences in mosaic cycles or in stochastic dynamic landscapes that emerged from the interplay of several processes, and to predict and explain their spatial and temporal characteristics. The current knowledge of how changing spatial attributes affect biodiversity, habitats, and ecosystem functions is limited by the scarcity of studies that explicitly consider the shifting in time of the four spatial attributes together. [Copyright &y& Elsevier]

Abstract: A two step protocol has been set up to selectively conjugate PEG to buried amino acids of proteins. The process involves site-specific glycation followed by PEGylation of the oxidized glycosides. Aimed at glycating the cysteine groups of proteins, two maleimide-glycosylic linkers have been synthesised: galactosyl-glucono-CO–NH–(CH2)12–NH–CO–(CH2)2-maleimide and maltosyl-glucono-CO–NH–(CH2)12–NH–CO–(CH2)2-maleimide. The linkers were extensively characterized by 1H NMR, FT-IR, ESI–TOF mass spectrometry and colorimetric assays. Complete conjugation of the activated linkers to Cys34 of human serum albumin was obtained in about 2h. The selective oxidation of the galactosyl and maltosyl moieties by periodate treatment yielded two and three available aldehyde groups, respectively. The PEG-hydrazide conjugation to the aldehyde groups was found to be 100% in about 40h, whereas less than 30% protein modification was obtained by direct conjugation of commercial PEG-maleimide to Cys34. The pH dependent PEG-glycosyl hydrazone bond hydrolysis at various pH values was verified. PEG release was faster under mild acidic and basic conditions than at neutral pH. Furthermore, the maltosyl derivatives, by virtue of the higher number of coupled PEG chains, showed a slower protein release as compared to the galactosyl counterpart, indicating that the choice of the glycosylic linker allows for control of protein release kinetics. [Copyright &y& Elsevier]

Abstract: Cyclodextrin–PEG hydrogels were prepared by reaction of hexamethlyene isocyanate-activated β-cyclodextrins with 1.9kDa NH2 yph name="sbnd" />NH2. The reaction was carried out in anhydrous dimethylsulfoxide by using 0.25:1, 0.33:1, 0.5:1, 0.67:1, 1:1, and 2:1 CD/PEG molar ratios. The addition of acetic acid to the reaction mixture was found to slow the cross-linking reaction, yielding homogeneous matrices. The mechanical characterization indicated that the elasticity of the matrices increased as the CD content in the hydrogel increased while the elongation was irrespective of the hydrogel composition. By incubation in water and ethanol, the hydrogels underwent complete swelling in 5–10min. The water up-take increased logarithmically as the CD/PEG ratio decreased to reach a swelling degree of 800% (swollen hydrogel/dry hydrogel, w/w%). The ethanol uptake increased with a power correlation as the CD/PEG ratio decreased to reach a swelling degree of about 1000% with 0.25:1 CD/PEG hydrogel. Lysozyme, β-estradiol, and quinine were loaded by swell embedding. The lysozyme loading increased as the CD/PEG ratio decreased while the incorporation of β-estradiol and quinine displayed inverse correlation with respect to the CD/PEG ratio. The maximal incorporation (loaded drug/dry hydrogel, w/w%) for lysozyme, β-estradiol and quinine was 2, 0.6, and 2.4%, respectively. Lysozyme was quickly released from the matrices, and the release was faster as the CD/PEG ratio decreased. Also, β-estradiol and quinine release rates were inversely proportional to the CD/PEG ratio, but in these cases, the release profiles were strongly affected by the drug interaction with the hexamethylated β-cyclodextrins in the matrices. [Copyright &y& Elsevier]

The search for new therapeutic approaches to haematological malignant disease involves exploitation of the antitumour potential of adaptive immunity-the most specific killing system against cancer currently known. Here, we summarise immunological strategies behind active specific immunotherapy, and describe the clinical and immunological results from trials published to date. Available data in humans support the hypothesis that various vaccination regimens can polarise adaptive immunity towards effective control of cancer-cell growth. However, the exploratory nature of clinical studies done thus far does not allow any cancer vaccine to be used as standard treatment for haematological malignant disorders. Because the cause of disease recurrence is the presence of minimal residual disease after conventional treatments, the adjuvant setting might be the most appropriate therapeutic strategy for active specific immunotherapy, when the immunosuppressive effects of bulky disease are virtually absent and when the effector-target ratio is favourable. In the near future, completion of randomised phase III trials as well as clinical implementation of the most recent insights into tumour immunology that aim to overcome immune tolerance towards malignant cells should allow investigators to define the actual role of vaccines in the management of haematological tumours. [ABSTRACT FROM AUTHOR]

• Spontaneous woodlands support a range of social, cultural and ecological services. • Italian urban plans are deficient in spontaneous urban woodlands consideration. • Recognition of spontaneous woodlands recognition in urban plans can support regeneration strategies. • Citizens are pivotal to maintain and value spontaneous urban woodlands. Urban forests have manifold social, economic, cultural and ecological benefits and are major components of the urban green infrastructure. Among them, spontaneous urban woodlands develop unintentionally on abandoned lands in both growing and shrinking cities and deserve additional attention. We aimed to describe the planning and social processes linked to failures and successes in recognising spontaneous woodlands in Italy. We collected data on the woodland area characteristics, urban settings, and former land use as well as on the planning and property evolution (e.g. land use zone designations) and citizens involvement for 19 sites in 13 representative Italian cities. Our results highlighted that spontaneous woodlands are heterogeneous in size and age, and grow on a variety of previous land uses, with residential and industrial being the most dominant. More than half of the urban plans designated land uses that require new soil sealing and tree plantations instead of maintaining the existing woodlands. Only in four case studies, urban plans recognised the spontaneous woodland, at least partially, as an element of the city's green infrastructure. We pinpoint an overall deficiency of the planning process in considering spontaneous urban woodlands, although with some exceptions that can represent models for future planning. The role of citizens seemed pivotal, even if not necessarily decisive, in the promotion and maintenance of these woodlands as a real social and ecological asset. A complex and modern array of approaches should capitalise on the potential benefits of spontaneous urban woodlands with the participation of citizens as a strong element of governance. [ABSTRACT FROM AUTHOR]

• General and stress relief preferences seem to be relatively consistent. • Presence of people in green spaces is a very important feature for visitor preferences. • People and presence of manmade elements are positive features for perceived safety. Public urban green spaces are crucial for citizens' wellbeing and are an important part of daily life in cities. To maximize their benefits to quality of life a thorough knowledge of citizens' preferences and preference heterogeneity is crucial in the planning and design of urban green spaces. This study investigated visitors' perception of typical green spaces, with a focus on vegetation structure and the presence of typical historic city walls, as well as preferences within the context of perceived stress and safety. We conducted this study in the historic city of Padua in north-eastern Italy. In 2017, face-to-face interviews of citizens were held and choice sets, based on modified images of different green space scenarios, were used to test users' preferences connected to both stress relief and safety perception. The study highlighted that general, stress relief and safety perception related preferences of the respondents depend on different site characteristics. Respondents preferred a complex but not too wild scenario with sparse trees and aesthetically appealing features such as colourful flowers. Historic walls had a negative effect on general preferences. While general preferences were very similar to stress relief preferences, preferences within the context of safety differed for some attributes. It seems that the vegetation structure and the presence of features linked to human recreational uses are important factors in planning and designing urban green spaces. Management and planning should take into consideration what users demand from green spaces as this will influence their suitable design. [ABSTRACT FROM AUTHOR]