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We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Preventing SARS-CoV-2 infection is of utmost importance in allogeneic hematopoietic cell transplantation patients (allo-HCT), given their heightened susceptibility to adverse outcomes associated with SARS-CoV-2 infection. However, limited data are available regarding the immune response to COVID-19 vaccines in these subjects, particularly concerning the generation and persistence of spike-specific memory response. Here, we analyzed the spike-specific memory B cells in a cohort of allo-HCT recipients vaccinated with multiple doses of the mRNA-1273 vaccine and monitored the spike-specific antibody response from baseline up to one month after the fourth dose. After the primary vaccine series, the frequency of spike-specific B cells, detected within the pool of Ig-switched CD19+ cells, significantly increased. The booster dose further induced a significant expansion, reaching up to 0.28% of spike-specific B cells. The kinetics of this expansion were slower in the allo-HCT recipients compared to healthy controls. Spike-specific IgG and ACE2/RBD binding inhibition activity were observed in 80% of the allo-HCT recipients after the first two doses, with a significant increase after the third and fourth booster doses, including in the subjects who did not respond to the primary vaccine series. Additionally, 87% of the allo-HCT recipients exhibited positive cross-inhibition activity against the BA.1 variant. Our findings provide evidence that allo-HCT recipients need repeated doses of the mRNA-1273 vaccine to induceSARS-CoV-2 specific immune response similar to that observed in healthy individuals. This is particularly crucial for vulnerable individuals who may exhibit a limited response to the primary series of SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Elimination of virally infected or tumoral cells is mediated by cytotoxic T cells (CTL). Upon antigen recognition, CTLs assemble a specialized signaling and secretory domain at the interface with their target, the immune synapse (IS). During IS formation, CTLs acquire a transient polarity, marked by re-orientation of the centrosome and microtubule cytoskeleton toward the IS, thus directing the transport and delivery of the lytic granules to the target cell. Based on the implication that the kinase Aurora A has a role in CTL function, we hypothesized that its substrate, the mitotic regulator Polo-like kinase 1 (PLK1), might participate in CTL IS assembly. We demonstrate that PLK1 is phosphorylated upon TCR triggering and polarizes to the IS. PLK1 silencing or inhibition results in impaired IS assembly and function, as witnessed by defective synaptic accumulation of T cell receptors (TCRs), as well as compromised centrosome and lytic granule polarization to the IS, resulting in impaired target cell killing. This function is achieved by coupling early signaling to microtubule dynamics, a function pivotal for CTL-mediated cytotoxicity. These results identify PLK1 as a new player in CTL IS assembly and function. [ABSTRACT FROM AUTHOR]

Introduction: Escape from immunosurveillance is a hallmark of chronic lymphocytic leukemia (CLL) cells. In the protective niche of lymphoid organs, leukemic cells suppress the ability of T lymphocytes to form the immune synapse (IS), thereby hampering T-cell mediated anti-tumoral activities. By binding its cognate receptor PD-1 at the surface of T lymphocytes, the inhibitory ligand PDL1, which is overexpressed in CLL cells, mediates the T-cell suppressive activities of CLL cells. However, the molecular mechanism underlying PD-L1 overexpression in CLL cells remains unknown. We have previously reported a defective expression of the pro-apoptotic and pro-oxidant adaptor p66Shc in CLL cells, which is causally related to an impairment in intracellular reactive oxygen species (ROS) production and to the activation of the ROS-sensitive transcription factor NF-B. The fact that PD-L1 expression is regulated by NF-B suggests a mechanistic relationship between p66Shc deficiency and PD-L1 overexpression in CLL cells. Methods: 62 treatment-naive CLL patients and 43 healthy donors were included in this study. PD-L1 and p66Shc expression was quantified in B cells by flow cytometry and qRT-PCR. IS architecture and local signaling was assessed by flow cytometry and confocal microscopy. CD8+ cell killing activity was assessed by flow cytometry. Results: Here we show that residual p66Shc expression in leukemic cells isolated both from CLL patients and from the CLL mouse model Eµ-TCL1 inversely correlated with PD-L1 expression. We also show that the PD-L1 increase prevented leukemic cells from forming ISs with T lymphocytes. Reconstitution of p66Shc, but not of a ROS-defective mutant, in both CLL cells and the CLLderived cell line MEC-1, enhanced intracellular ROS and decreased PD-L1 expression. Similar results were obtained following treatment of CLL cells with H2O2 as exogenous source of ROS, that normalized PD-L1 expression and recovered IS formation. Discussion: Our data provide direct evidence that the p66Shc-deficiency-related ROS depletion in CLL cells concurs to enhance PD-L1 expression and provides a mechanistic basis for the suppression of T cell-mediated anti-tumoral functions in the immunosuppressive lymphoid niche. [ABSTRACT FROM AUTHOR]

Introduction: Escape from immunosurveillance is a hallmark of chronic lymphocytic leukemia (CLL) cells. In the protective niche of lymphoid organs, leukemic cells suppress the ability of T lymphocytes to form the immune synapse (IS), thereby hampering T-cell mediated anti-tumoral activities. By binding its cognate receptor PD-1 at the surface of T lymphocytes, the inhibitory ligand PD-L1, which is overexpressed in CLL cells, mediates the T-cell suppressive activities of CLL cells. However, the molecular mechanism underlying PD-L1 overexpression in CLL cells remains unknown. We have previously reported a defective expression of the pro-apoptotic and pro-oxidant adaptor p66Shc in CLL cells, which is causally related to an impairment in intracellular reactive oxygen species (ROS) production and to the activation of the ROS-sensitive transcription factor NF-κB. The fact that PD-L1 expression is regulated by NF-κB suggests a mechanistic relationship between p66Shc deficiency and PD-L1 overexpression in CLL cells. Methods: 62 treatment-naive CLL patients and 43 healthy donors were included in this study. PD-L1 and p66Shc expression was quantified in B cells by flow cytometry and qRT-PCR. IS architecture and local signaling was assessed by flow cytometry and confocal microscopy. CD8+ cell killing activity was assessed by flow cytometry. Results: Here we show that residual p66Shc expression in leukemic cells isolated both from CLL patients and from the CLL mouse model Eμ-TCL1 inversely correlated with PD-L1 expression. We also show that the PD-L1 increase prevented leukemic cells from forming ISs with T lymphocytes. Reconstitution of p66Shc, but not of a ROS-defective mutant, in both CLL cells and the CLL-derived cell line MEC-1, enhanced intracellular ROS and decreased PD-L1 expression. Similar results were obtained following treatment of CLL cells with H2O2 as exogenous source of ROS, that normalized PD-L1 expression and recovered IS formation. Discussion: Our data provide direct evidence that the p66Shc-deficiency-related ROS depletion in CLL cells concurs to enhance PD-L1 expression and provides a mechanistic basis for the suppression of T cell-mediated anti-tumoral functions in the immunosuppressive lymphoid niche. [ABSTRACT FROM AUTHOR]

Background: The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC) is a major hurdle for immune checkpoint inhibitor-based therapies. Hence characterization of the signaling pathways driving T cell exhaustion within TME is a critical need for the discovery of novel therapeutic targets and the development of effective therapies. We previously showed that (i) the adaptor protein Rai is a negative regulator of T cell receptor signaling and T helper 1 (Th1)/Th17 cell differentiation; and (ii) Rai deficiency is implicated in the hyperactive phenotype of T cells in autoimmune diseases. Methods: The expression level of Rai was measured by qRT-PCR in paired peripheral blood T cells and T cells infiltrating tumor tissue and the normal adjacent tissue in CRC patients. The impact of hypoxia-inducible factor (HIF)-1α on Rai expression was evaluated in T cells exposed to hypoxia and by performing chromatin immunoprecipitation assays and RNA interference assays. The mechanism by which upregulation of Rai in T cells promotes T cell exhaustion were evaluated by flow cytometric, qRT-PCR and western blot analyses. Results: We show that Rai is a novel HIF-1α-responsive gene that is upregulated in tumor infiltrating lymphocytes of CRC patients compared to patient-matched circulating T cells. Rai upregulation in T cells promoted Programmed cell Death protein (PD)-1 expression and impaired antigen-dependent degranulation of CD8+ T cells by inhibiting phospho-inactivation of glycogen synthase kinase (GSK)-3, a central regulator of PD-1 expression and T cell-mediated anti-tumor immunity. Conclusions: Our data identify Rai as a hitherto unknown regulator of the TME-induced exhausted phenotype of human T cells. [ABSTRACT FROM AUTHOR]

The rhizosphere effect occurring at the root-soil interface has increasingly been shown to play a key role in plant fitness and soil functionality, influencing plants resilience. Here, for the first time, we investigated whether the rootstock genotype on which Vitis vinifera L. cultivar Falanghina is grafted can influence the rhizosphere microbiome. Specifically, we evaluated to which extent the 5BB and 1103P rootstocks are able to shape microbial diversity of rhizosphere environment. Moreover, we explored the potential function of microbial community and its shift under plant genotype influence. We investigated seven vineyards subjected to the same pedo-climatic conditions, similar age, training system and management and collected twelve rhizosphere soil samples for metagenomic analyses and composite soil samples for physical-chemical properties. In this study, we used 16S rRNA gene-based metagenomic analysis to investigate the rhizosphere bacterial diversity and composition. Liner discriminant analysis effect size (LEFSe) was conducted for metagenomic biomarker discovery. The functional composition of sampled communities was determined using PICRUSt, which is based on marker gene sequencing profiles. Soil analyses involved the determination of texture, pH, Cation Exchange Capacity (CSC), Organic Carbon (OC), electrical conductivity (EC), calcium (Ca), magnesium (Mg), potassium (K) content, Phosphorous (P), nitrogen (N). The latter revealed that soil features were quite homogenous. The metagenomic data showed that the bacterial alpha-diversity (Observed OTUs) significantly increased in 1103P rhizosphere microbiota. Irrespective of cultivar, Pseudomonadota was the dominant phylum, followed by Actinomycetota > Bacteroidota > Thermoproteota. However, Actinomycetota was the major marker phyla differentiating the rhizosphere microbial communities associated with the different rootstock types. At the genus level, several taxa belonging to Actinomycetota and Alphaproteobacteria classes were enriched in 1103P genotype rhizosphere. Investigating the potential functional profile, we found that most key enzyme-encoding genes involved in N cycling were significantly more abundant in 5BB rootstock rhizosphere soil. However, we found that 1103P rhizosphere was enriched in genes involved in C cycle and Plant Growth Promotion (PGP) functionality. Our results suggest that the different rootstocks not only recruit specific bacterial communities, but also specific functional traits within the same environment. [ABSTRACT FROM AUTHOR]

A recent study published in the Scandinavian Journal of Immunology explores the potential role of platelet HLA class I expression level in asymptomatic SARS-CoV-2 infection. The study found that individuals carrying the HLA-B*15:01 allele were more likely to remain asymptomatic after infection compared to those who did not carry the allele. Additionally, the study revealed a possible link between HLA allelic type and expression level on platelets, suggesting that higher expression of HLA-B*15:01 could enhance viral clearance and host immune response. Further research is needed to fully understand the impact of HLA expression and platelet subpopulations on SARS-CoV-2 infection and disease progression. [Extracted from the article]

Background The main purpose of our study was to evaluate the ability of renal functional reserve (RFR) to stratify the risk of acute kidney injury (AKI) occurrence within 100 days of hematopoietic stem cell transplantation (HSCT) and to predict any functional recovery or the onset of chronic kidney disease. A secondary aim was to identify the clinical/laboratory risk factors for the occurrence of AKI. Methods The study design is prospective observational. We enrolled 48 patients with normal basal glomerular filtration rate (bGFR) who underwent allogenic HSCT. A multiparameter assessment and the Renal Functional Reserve Test (RFR-T) using an oral protein load stress test were performed 15 days before the HSCT. Results Different RFRs corresponded to the same bGFR values. Of 48 patients, 29 (60%) developed AKI. Comparing the AKI group with the group that did not develop AKI, no statistically significant difference emerged in any characteristic related to demographic, clinical or multiparameter assessment variables except for the estimated GFR (eGFR). eGFR ≤100 mL/min/1.73 m2 was significantly related to the risk of developing AKI (Fisher's exact test, P  = .001). Moreover, RFR-T was lower in AKI+ patients vs AKI– patients, but did not allow statistical significance (28% vs 40%). In AKI patients, RFR >20% was associated with complete functional recovery (one-sided Fisher's exact test, P  = .041). The risk of failure to recover increases significantly when RFR ≤20% (odds ratio = 5.50, 95% confidence interval = 1.06–28.4). Conclusion RFR identifies subclinical functional deterioration conditions essential for post-AKI recovery. In our cohort of patients with no kidney disease (NKD), the degree of pre-HSCT eGFR is associated with AKI risk, and a reduction in pre-HSCT RFR above a threshold of 20% is related to complete renal functional recovery post-AKI. Identifying eGFR first and RFR second could help select patients who might benefit from changes in transplant management or early nephrological assessment. [ABSTRACT FROM AUTHOR]

The ecological transition and food and energy crises have revealed the issue of inner areas which, despite their vulnerabilities, seem to have become strategic in Italy. The renewed attention to inner areas highlights their potential for food and energy production and the need for a multidimensional sustainability approach to address issues of depopulation and resource waste. The paper aims to contribute to the debate on these topics and to stimulate research on territorial analysis and policies, also in virtue of the new awareness of the potential of inner areas, rich in human, cultural, natural and economic resources. To find a solution to the economic and social revitalization of these areas, it is necessary to leave the mainstream of global competition and take different paths, based on the enhancement of local resources and the direct involvement of citizens/consumers through the promotion of a model of "proximity economy". Within this logic, foods from minor supply chains in fragile areas can become the driver for a proximity economy model based on cooperation, participation, reciprocity, inclusion and the sharing of created value. [ABSTRACT FROM AUTHOR]

Purpose: Social Farming (SF) is an expression of agricultural diversification and multifunctionality, due to its ability to create positive externalities through the inclusion of vulnerable individuals. For this reason, products derived from SF are characterized by social quality attributes, which, however, are not often recognized by the market. This study aims to investigate the reasons behind the lacked recognition of the value created by SF analyzing the willingness to pay (WTP) for such products and the factors affecting citizen-consumers' purchasing behavior. Design/methodology/approach: Data were collected through a convenience sample (N = 350) via a web-based structured questionnaire. Psycho-attitudinal scales, previously validated in literature, were adopted to characterize the citizen-consumers interviewed. A logistic regression was run in order to determine those characteristics of respondents affecting their intention to purchase SF products, while an ordered logistic regression was performed to uncover the determinants of consumers' WTP for SF products. Findings: The results show the relevant role of the level of education, household size and ethical self-identity in affecting the willingness to support SF activities by paying a price premium for its products. Lack of availability and information about SF products are the main factors limiting their purchase. Originality/value: The study offers interesting results outlining future research fields about market penetration strategies and policy implications. [ABSTRACT FROM AUTHOR]

European policies, especially the 'farm-to-fork strategy', address the challenge posed by the ecological transition in agriculture setting up a new technological paradigm. In this context, collective smart innovations may play a crucial role, enabling to meet current citizen-consumers' needs as well as producing positive environmental and social externalities. Lately, wineries, in the attempt to improve the sustainability of production process and the creation of competitive advantages, reoriented their investments in research and development embracing smart innovations. The latter, when supported by appropriate models of corporate governance, can facilitate business decisions and create shared value. Despite its relevance, literature on the topic is still scarce. This study aims to investigate the role played by collective smart innovations and corporate governance in the sustainable and ecological transition of wineries and, specifically, wine cooperatives. The case study methodology was adopted investigating the collective innovation 'I mille per l'Aglianico' implemented by the Italian wine cooperative 'La Guardiense'. Results show that the collective smart innovation experienced by 'La Guardiense' had impacts in terms of internal economies, such as increase in sales and costs reduction; and in terms of external social economies, such as local development and environmental protection. [ABSTRACT FROM AUTHOR]

Keywords: B cells; Chronic lymphocytic leukemia (CLL); CRISPR/Cas9; mRNA; Screening EN B cells Chronic lymphocytic leukemia (CLL) CRISPR/Cas9 mRNA Screening 1362 1365 4 08/08/22 20220801 NES 220801 Robust methods for manipulation of human B cells, isolated from healthy donors and patients with B cell disorders, has the potential to significantly accelerate B cell research. To favor B-cell survival, we cultured electroporated cells in serum-free medium AIM-V that has been previously shown to better support survival of fragile anergic B cells from patients with B-cell chronic lymphocytic leukemia (CLL), compared to fetal bovine serum-supplemented medium [6]. Assessing gene function in human B cells: CRISPR/Cas9-based gene editing and mRNA-based gene expression in healthy and tumor cells To overcome the issue of low cell viability after electroporation, we optimized electroporation settings using freshly isolated human B cells and an in vitro produced mRNA encoding I GFP i on an electroporation system with bimodal pulsing strategy. [Extracted from the article]

Contracts represent key governance mechanisms along the supply chain to pursue collective sustainable strategies in line with new citizen-consumers' preferences for sustainable products. Adopting an embedded multiple case study approach, this paper explores and analyzes 11 cases of contractual relationships between Italian semolina and pasta producers and farmers in order to investigate whether sustainability strategies affect the design of contracts and the related consequences. Findings reveal that different sustainability strategies correspond to different design and combinations of (both monetary and nonmonetary) contractual incentives aimed to centralize property and decision rights. What emerges is that stronger sustainability strategies entail a higher degree of buyers' control over strategic investments (such as land and seeds) as well as wider provision of technical assistance and knowledge and innovation transfer toward farmers. Therefore, mutual gains seem at stake, even if socio-economic implications of the shift in decisional and control rights from farmers toward buyers shall be neglected, to ensure a better coherence with the farm to fork strategy and sustainable development goals. [ABSTRACT FROM AUTHOR]

Hypoxia is a component of both physiological and pathological conditions, including inflammation, solid tumors, and lymphoid tissues, where O2 demand is not balanced by O2 supply. During their lifespan, dendritic cells (DCs) are exposed to different pO2 and activate different adaptive responses, including autophagy, to preserve their viability and functions. Autophagy plays multiple roles in DC physiology. Very recently, we demonstrated that hypoxia shapes autophagy in DCs upon their differentiation state. Here, we proposed a role for PI3Ks, and especially class III PI3K/Vps34, that could be relevant in hypoxia-induced autophagy, in either immature or mature DCs. Hypoxia inhibited mTOR phosphorylation and activated a pro-autophagic program. By using different pharmacological inhibitors, we demonstrated that hypoxia-induced autophagy was mediated by PI3Ks, especially by Vps34. Furthermore, Vps34 expression was enhanced by LPS, a TLR4 ligand, along with the promotion of autophagy under hypoxia. The Vps34 inhibitor, SAR405, abolished hypoxia-induced autophagy, inhibited pro-survival signaling and viability, and increased the expression of proinflammatory cytokines. Our results underlined the impact of autophagy in the maintenance of DC homeostasis at both cell survival and inflammatory response levels, therefore, contributing to a better understanding of the significance of autophagy in DC physiology and pathology. [ABSTRACT FROM AUTHOR]

Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54–3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53–3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41–7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor. [ABSTRACT FROM AUTHOR]

This study compared corneal thickness (CT) changes obtained with specular microscopy (SM) and a rotating Scheimpflug camera (RSC) after conventional phacoemulsification surgery (PS). One hundred sixty six eyes of 83 patients were analyzed before and one month after PS. One eye underwent PS, while the fellow phakic one was used as control. CT was measured with SM at the center of the cornea and with RSC at the pupil center, at the corneal apex and at the thinnest point. In the operated eye, SM showed a larger CT mean increase than those one detected at the three different measurements' points evaluated by RSC. Inversely, in the fellow phakic eye, SM showed a greater CT mean decrease than those one registered by RSC at its three measurement's points. Thus, one month after surgery, even if cornea appears clear at the slit-lamp, a significant thickness increase is still present. This is even more evident if the slight decrease of the fellow phakic eye is considered. The differences between the two devices are probably related to the different measured areas. [ABSTRACT FROM AUTHOR]

This study aims at estimating the wheat yield response to future challenges (land degradation and climate change) through a statistical emulator. Data from Global Agro‐ecological Zones on the overall wheat yields of 254 provinces for nine main wheat‐producing countries and corresponding climate and land suitability information were collected to estimate the statistical relationship between regressors and wheat yields. Once the statistical emulator was calibrated, three scenarios were developed to predict, separately and jointly, the impact of climate change and land degradation on wheat yields and productions in 2050 using the global climate model ECHAM4 information under the B2 scenario with the CO2 fertilization effect. Results showed that under temperature and precipitation projections wheat yield would increase on average by 8% (first scenario); however, the impact of future land suitability (second scenario) on wheat yields would be negative, lowering the average yield (−5%), and overall wheat production (−14%). Combining both effects in the third scenario, future wheat yields would increase by 4.6%, while overall production will decrease by 5.5% since the harvest area will be reduced by 9.7%. Thus, land degradation more than climate change is likely to pose significant challenges for overall wheat production in the future. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the correlation between corneal thickness (CT) measurements obtained with two Scheimpflug devices, Pentacam HR and Precisio, and to elaborate, if necessary, a regression formula which could make these results comparable. Design: Retrospective, Comparative, Observational study. Setting: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana" University of Salerno, Italy Methods: One hundred twenty four healthy eyes of 124 volunteers (65 males; range: 20–32 years; mean age of 24.8 ± 1.7) were included in this study. CT was measured using Pentacam HR and Precisio in three different points: the pupil center (PC), the corneal apex (CA) and the thinnest point (TP). Results: CT obtained with both devices at the PC, at the CA and at the TP showed a good correlation (r = 0.97, r = 0.97, r = 0.97, respectively), but Pentacam HR measurements were significantly thicker than those provided by Precisio (p < 0.01). The differences between Pentacam HR and Precisio were 21.9 ± 8.8 μm at the PC, 21.9 ± 8.9 μm at the CA, 19.1 ± 9.0 μm at the TP. The calculated regression formulas were: y = 0.9558x + 2.3196 for the PC, y = 0.9519x + 4.5626 for the CA, y = 0.9364x + 15.436 for the TP, where x is the CT measured with Pentacam HR and y is the Precisio measurement. Conclusions: The findings provided by this study highlight that Precisio measures thinner corneas compared to Pentacam HR. The identified regression formulas could be utilized to make interchangeable the results obtained with these two devices. [ABSTRACT FROM AUTHOR]

The paper aims at analyzing the effect of institutional quality on labor productivity in the agricultural sector. To meet this aim, a Gaussian log-linear model was applied to 773 vineyard farms, located in 71 Italian provinces. The applied methodology enabled to quantify the overall impact of the institutional quality on labor productivity by discriminating with respect to the Italian regions and macro-areas (i.e. North, South or Central Italy). The findings of the investigation show a positive effect of the institutional quality on labor productivity, with an overall impact of 39%. Moreover, huge differences among Italian regions and macro-areas were detected. The study findings provide recommendations for academics and policy-makers to improve both theoretical and practical aspects. [ABSTRACT FROM AUTHOR]

During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions. [ABSTRACT FROM AUTHOR]

The revealed preference for dominated insurance-based personal pension plans (PPPs) in Italy is a decade-long puzzle. I surmise that a motivation from the supply side is a sales force factor deriving from the geographical distribution of financial providers, including the countrywide network of the state controlled Post Office. I provide supporting evidence using three biennial waves of the Bank of Italy's survey on household finances from 2010 to 2014. The time interval includes a public pension system reform sharply raising the statutory age retirement, legislated in December 2011 to defuse a sovereign debt crisis. I show that the salience effect on the awareness of the benefits of supplementing lower perspective public pensions with PPPs increased the explanatory power of financial strength indicators. Exploiting a module in the 2010 wave I estimate a surprising decrease in the probability of subscription to PPPs in 2014 associated with the indicator for the highest financial literacy level. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to analyse the value creation processes in multifunctional wineries. Specifically, the paper poses the following research questions: can the creation of public goods (i.e. multifunctionality) open up new paths of value creation for wineries? And if so, can multifunctionality be only compensated through policy instruments? Or, is there a form of market compensation? Design/methodology/approach: An empirical analysis was carried out on selected wineries that sell directly. The study implemented the "value portfolio" model that identifies specific variables, both internal and external to the farm, which contribute to the value creation. The methodology adopted is a structural equation modeling (SEM) approach that offers a theoretical basis for developing an understanding of the relationships between group of variables. Findings: The empirical analysis confirms the assumptions developed. Indeed, the localized public goods generated by multifunctional farms can benefit from compensation on the market through the direct sale of products and services. Originality/value: The study's findings are quite innovative in the field of agricultural economics and open the way for interesting policy implications. [ABSTRACT FROM AUTHOR]

The current paper investigates consumers' consumption behavior and preferences for craft beer. More specifically, it uncovers consumers' consumption habits and perception about craft beer, as well as their preferences for 13 beer attributes drawn from the literature. The analysis was carried out in Italy by administering a structured questionnaire to 323 consumers. Best-Worst Scaling was used to detect consumers' preferences towards the 13 craft beer attributes. The latter were then ranked on the basis of their best-worst scores to identify the level of importance Italian consumers assign to the different attributes. The study findings reveal that Italian craft beer consumers are young, well-educated, and employed. They drink craft beer more than once per month, mainly in pub and with friends and colleagues. Craft beer is perceived with higher quality and different flavors, while compared with a commercial beer, it results tastier, more genuine, and natural. As for the beer attributes, Italians prefer taste, fermentation process, and color, while store promotion, brand, and price rank as the least important. The study findings offer several implications for brewers and marketers involved in the beer sector. Based on the preferences detected, breweries should adapt their product offer to meet craft beer consumers' expectations. [ABSTRACT FROM AUTHOR]

This special issue of Agricultural and Food Economics consists of four articles that were part of the scientific programme of the First SIDEA-SIEA Joint Conference, held in Bisceglie in September 2017. The conference afforded agricultural economists the opportunity to reflect on cooperative strategies to promote competitiveness of the agri-food supply chain, with a focus on environmental quality and social sustainability. The selected articles address these themes from different perspectives: those of firms, of consumers, and of policy makers, stressing that sustainability calls for the active participation of all of the actors. The case studies presented propose an effective interpretation of the strategies for value creation with respect to the challenges of climate change, food waste management, the development of marginal rural areas, and that of the fish sector. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to investigate consumer's acceptance toward product innovation in the agri-food sector, uncovering consumers' characteristics able to encourage food innovation acceptance. Design/methodology/approach: The analysis was carried out by administering a web-based structured questionnaire to a convenient sample of 443 Italian consumers. The study relies on consumers' willingness to pay (WTP) to assess consumers' acceptance toward the innovative product, while the Food-Related Lifestyle scale was applied to perform a cluster analysis aiming at detecting the attitude of consumers toward innovations in a traditional food. Findings: The study findings showed a clear openness of consumers toward product innovation. Indeed, consumers' WTP for the innovative product was far higher than the traditional one. Further, two out of three consumers' groups detected (i.e. pro-innovation and rational adopters) exhibit a broad correlation between the innovative product attributes and consumers' psychographics characteristics, revealing the existence of a large number of potential consumers. Originality/value: The contribution of the paper to the current literature is twofold. First, it focused on an emerging topic for the agri-food sector (i.e. product innovation) whereby research works are still scarce. Second, product innovation was addressed toward a traditional food that is mostly reluctant to innovation due to consumers' resistance and skepticism. [ABSTRACT FROM AUTHOR]

A "farmers' market" identifies a common area where farmers meet periodically to sell food products which do not need to be processed before consumption. Farmers' markets have recently experienced steady growth mainly due to increasing demand for traditional foods and rising consumers' interest towards locally produced food products. It is also the case that they provide transparency along the supply chain and decrease information asymmetries. This study attempts to define the farmers and consumers of farmers' markets in terms of both their socio-demographic and their attitudinal characteristics. Data gathering was performed carrying out face-to-face interviews with sixty farmers and consumers. The study findings show that the majority of consumers purchasing at farmers' markets are women, with an average age of 49 and with a high level of education. They attach great value to the availability of fresh and organic products with a good value for money. Farmers, by contrast, are mainly male, with an average age of 45 years, a high school degree and several years of experience in farming. They value more the creation of a direct and durable relationship with consumers in order to convey information about the quality and authenticity of their products. The study offers useful implications to policy makers on how to encourage the creation of farmers' markets as well as spread the shared value created among farmers and consumers. [ABSTRACT FROM AUTHOR]

BACKGROUND This study, by combining sensory and experimental economics techniques, aims to analyse to what extent the production process, and the information about it, may affect consumer preferences. Sparkling wines produced by Champenoise and Charmat methods were the object of the study. A quantitative descriptive sensory analysis with a trained panel and non‐hypothetical auctions combined with hedonic ratings involving young wine consumers (N = 100), under different information scenarios (Blind, Info and Info Taste), were performed. RESULTS: The findings show that the production process impacts both the sensory profile of sparkling wines and consumer expectations. In particular, the hedonic ratings revealed that when tasting the products, both with no information on the production process (Blind) and with such information (Info Taste), the consumers preferred the Charmat wines. On the contrary, when detailed information on the production methods was given without tasting (Info), consumers liked the two Champenoise wines more. CONCLUSION: It can be concluded that sensory and non‐sensory attributes of sparkling wines affect consumers' preferences. Specifically, the study suggests that production process information strongly impacts liking expectations, while not affecting informed liking. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

References 1 Raval R, Shen J, Lau D, Ferguson N, Kelly T, Daniels J. Comparison of three point-of-care ultrasound views and MRI measurements for optic nerve sheath diameter: a prospective validity study. 10.1007/s12028-019-00881-7. 31792700 2 De Bernardo M, Vitiello L, Cornetta P, Rosa N. Ocular ultrasound evaluation of optic nerve sheath diameter in military environments. In our opinion, this result should have been expected because the authors used the ultrasound B-scan technique. [Extracted from the article]

Reference 1 Fallerini C. SELP Asp603Asn and severe thrombosis in COVID-19 males. B Correction: J Hematol Oncol (2021) 14:123 b https://doi.org/10.1186/s13045-021-01136-9 The original article [[1]] mistakenly omitted a sentence in the Acknowledgements section which the authors include ahead: 'Two of several authors of this publication are members of the European Reference Network for rare haematological diseases EuroBloodNet.'. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

The reform of Common Agricultural Policy for 2014-2020 aims at promoting greater competitiveness, efficient use of public goods, food security, preservation of the environment and specific action against climate change, social and territorial equilibrium, and a more inclusive rural development. The economic crisis of the last years, the globalization, the increasing pressure on natural resources, the increasing diversity of agriculture and rural areas in the new enlarged Europe, and citizens' expectations regarding the environment, safety and food quality, health and welfare, preservation of the countryside, biodiversity and climate change, and the unequal distribution of resources are some of the major issues that this policy has faced, in a production context directed by principles of fairness and efficiency. The policy instruments to address these challenges and achieve specific objectives appear greatly transformed and made up of two complementary pillars (direct payments and market measures, the first, and rural development, the second). The perspectives that the new Common Agricultural Policy provides in order to reach a competitive repositioning of the European agricultural and rural systems have been the theme of the 51st SIDEA Conference aimed at promoting a scientific debate on implementation of this policy in Italy. The papers selected for this special issue focus on the new perspectives for European farms, agri-food supply chains, and rural territories of the new Common Agricultural Policy. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor. [ABSTRACT FROM AUTHOR]

We provide an empirical assessment of the suggestion, based on Severo (2012), to use a systemic liquidity risk index (SLRI) for estimating liquidity premia that could be charged on large banks as a compensation for the implicit liquidity support obtained from public authorities (Blancheret al., 2013). To this end we compute, over the period January 2004–December 2012, a parsimonious and fully documented SLRI. We also investigate its statistical significance in explaining the level and variability of stock returns for a group of large international banks across the subprime and the Eurozone sovereign debt crises. Main findings are two: our more parsimonious SLRI is close to Severo’s but provides a stronger signal of liquidity stress and recovery episodes; we consistently fail to detect, within and across the two crises, a stable group of banks among the global systemically important ones listed by the Financial Stability Board. [ABSTRACT FROM PUBLISHER]

They compared the ONSD measurements provided by magnetic resonance imaging (MRI) with the ultrasound findings, also analyzing the relationship between these ultrasound measurements and intracranial pressure values directly measured through external ventricular drainage [[1]]. In conclusion, the authors' statement that ultrasound ONSD measurements "cannot be presumed to be related to simultaneous ICP values" [[1]] could be explained by the above-discussed B-scan limitations. [Extracted from the article]

The problem of studying the causes of obesity is largely discussed in the literature by experts in nutrition and related diseases and is of particular interest in most recent years among scholars of business disciplines, especially as regards the impact on socio-health costs. After an overview of the geographical differences of obesity, related not only to eating habits, but also to lifestyles as well as hereditary factors, the purpose of this paper is try to trace the main functional relationships between BMI and health-care costs through the use of Multiple Corrispondence Analysis and Partial Least Squares Regression. [ABSTRACT FROM AUTHOR]

Social farming (SF) spread across Europe in recent decades. It represents an expression of agriculture diversification and performs a social function expressed through vulnerable individuals' social inclusion. As a result, SF is able to generate positive externalities and thus contribute to social wellbeing. Despite benefits, SF faces several issues related to its dissemination. Although in recent years scholars have been approaching this topic, much remains to be researched. Therefore, the purpose of this study was to investigate, through a systematic review, drivers and barriers related to the spread of this phenomenon. Results showed that factors such as the lack of information on SF, farmers' mental limitations and the lack of economic resources, as well as excessive bureaucratization, could hamper the spread of SF. On the other hand, ethical production, new income sources, sustainable rural development and new employment opportunities can encourage the dissemination of such practices. In order to overcome the barriers and emphasize the drivers pointed out by this study, the role of policymakers is essential, as they should promote information and training activities for farmers and consumers in order to increase awareness of SF social value and encourage a collective approach to SF practices. [ABSTRACT FROM AUTHOR]

Background: Allografting induces long-term molecular remissions and possibly cure in myeloma patients. The development of non-myeloablative conditionings has reduced the transplant-related mortality (TRM) associated with myeloablation and extended the eligible age for transplantation. Moreover, high response rates are reported especially when allografting is preceded by cytoreductive high-dose chemotherapy. We investigated the feasibility of unrelated donor non-myeloablative transplantation as either part of the initial treatment plan or as salvage treatment in heavily pretreated patients. Methods: Twenty-two patients underwent non-myeloablative allografting, 10 as part of their initial treatment and 12 at relapse. Donors were matched for HLA-A, B, C, DRB1 and DQB1 by high-resolution typing. Only one single class I allele disparity was allowed. Conditioning consisted of fludarabine 90 mg/m2 and 2 Gy total body irradiation. Graft-vs.-host disease (GVHD) prophylaxis included cyclosporin and mycophenolate mofetil. Results: All patients except two (91%) readily engrafted. After a median follow-up of 20 (10–30) months, incidences of grade II-IV acute and extensive chronic GVHD were 50% and 61%. Overall response (OR) was 55%, with four (20%) complete and seven (35%) partial remissions. However, in patients allografted up-front OR was 89% whereas in the heavily pretreated group OR was 27% ( P = 0.01). Two-year overall and event-free survivals were both 79% in the group transplanted up-front and 27% and 25% among relapsed patients ( P = 0.025 and P = 0.006, respectively). Overall, six patients died of TRM and three of disease progression. Conclusions: Unrelated donor non-myeloablative allografting is feasible in myeloma. Disease control appears more pronounced when patients are treated soon after diagnosis. [ABSTRACT FROM AUTHOR]

Background and objective: Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder which is treated effectively by interferon-alpha (IFN- α), deoxycoformycin (DCF) and 2-clorodeoxyadenosine (2-CdA). As a third of patients treated with DCF do not achieve a complete remission (CR) and many of them tend to relapse, we evaluated the potential role of IFN- α, randomly administered after DCF, in increasing the number of patients attaining CR and/or duration of CR. Methods: From March 1997 to December 2000, 167 previously untreated HCL patients, from 37 Italian institutions, were enrolled in the study. A total of 138 males and 29 females, with a median age of 55 yr were included in the study. All patients received six courses of DCF 4 mg/m2 i.v. every other week and then two additional courses once a month. Complete and partial responders were randomly assigned to receive or not receive IFN- α at a dose of 3 MU s.c. three times a week for 6 months. Results: Of the 167 patients enrolled in the study, 145 (86.8%) obtained a CR or a partial remission (PR) and were therefore suitable for randomization. One hundred and thirty-five patients were successively randomized to receive IFN- α (63 cases; arm A) or not (72 cases; arm B). Progression of disease was observed in eight (arm A) and 12 (arm B) patients with a median time of 27.8 and 26.9 months, respectively. As far as the improvement in response was concerned, no significant difference in the two subgroups was observed. In fact, five patients in arm A and six patients in arm B showing a good PR at the end of DCF therapy, subsequently attained a late CR. Conclusions: From our data there does not appear to be any significant role for IFN- α in improving the proportion and the duration of CR in HCL patients previously treated with DCF. [ABSTRACT FROM AUTHOR]

Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For this reason, leukemic patients with severe fungal infection are usually excluded from conventional allotransplantation. Recently, some authors suggested a role for non-myeloablative hematopoietic stem cell transplantation (HSCT) in this subset of patients. We used this therapeutic approach in a patient with high-risk acute myeloid leukemia in second complete remission (CR) with pre-existing hepatic aspergillosis refractory to conventional anti-fungal therapy. A complete regression of hepatic lesions was observed after 3 months from allogeneic stem cell transplantation. Our work confirms previous reports suggesting that non-myeloablative HSCT is effective in patients not eligible for conventional transplantation because of invasive aspergillosis. [ABSTRACT FROM AUTHOR]

Italian firms are top users of trade credit in an international comparison. The paper offers some clues to the determinants of this stylized fact exploiting the answers of about 1900 manufacturing firms on a wide range of contractual features, separately for domestic and foreign customers. The main finding of the univariate analysis is that, with the almost totality of transactions made on credit, there is no evidence that this way of financing is more expensive than loans. An econometric investigation shows that discounts offered have the expected effect of reducing payment delays mostly for customers located abroad, where customary credit periods are shorter and creditors' rights protection is more effective. The result is consistent with the poor explanatory power of discounts received in regressions for the trade debt period of domestic firms. [ABSTRACT FROM AUTHOR]

PURPOSE: To assess the validity of intraocular lens (IOL) power calculations utilizing a theoretical variable refractive index correlated to axial length after myopic photorefractive keratectomy (PRK) in a clinical simulation and in patients who underwent cataract surgery after PRK for myopia. METHODS: Our study included 374 eyes of 300 patients who had PRK for myopia (-2.00 to -12.00 D, mean -4.83± 2.57 D), divided into three groups: Group I had 44 eyes with small ablation zones of 5 to 5.5 mm; Group II had 49 eyes with large ablation zones of 6 to 7 mm; Group III was the control group of 281 eyes (201 patients; 87 males and 114 females) with small and large ablation zones. PRK was performed using the Aesculap- Meditec MEL 60/94 and MEL 70 lasers, and the corneal power was acquired by corneal topography (EyeSys 2000) and a Nidek KM-800 keratometer. RESULTS: There was a higher correlation between corneal power and both the change in refraction and axial length when calculated using keratometric measurements. IOL power calculated using keratometric postoperative PRK power was underestimated. The difference between the mean calculated and actual IOL power for emmetropia was 4.30 ±2.34 D. A theoretical variable refractive index (obtained from eyes treated with large PRK ablation zones) that correlated with axial length provided the correct keratometric postoperative PRK power: difference between mean calculated and mean actual IOL power was 0.42 ±1.23 D. CONCLUSIONS: We propose a theoretical variable refractive index that is correlated to axial length. Utilizing this keratometric correct power, we calculated IOL power similar to that for emmetropia. [ABSTRACT FROM AUTHOR]