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Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01). A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×10 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×10 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively. The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT03373097.).

Platelet factor 4 (PF4) is a protein with a pro-clotting function expressed by activated platelets with a high affinity for anionic glycosaminoglycans present on the platelet surface. It has been shown that the positively charged surface of PF4 tetramer interacts with the negatively charged regions of β2glycoprotein I (β2GPI) domains, stabilising the link between the antigen and the phospholipid surface, thus increasing the possibility of binding with the respective antibodies. In particular, a tetramer of PF4 selectively binds two molecules of β2GPI, favouring the dimerization of the same, which is crucial in platelet activation and therefore in thrombotic manifestations of antiphospholipid syndrome (aPS). PF4 may be a common denominator in syndromes such as aPS and heparin-induced thrombocytopenia (HIT), which share similar clinical manifestations as thrombocytopenia and thrombosis. Other syndromes, which share the same clinical and laboratory features of HIT despite not having previously received heparin, appear to be associated with the presence of anti-PF4 antibodies. Such pathologies could only be explained by HIT antibodies with heparin-independent platelet-activating properties. One of these could be vaccine-induced Immune thrombotic thrombocytopenia (VITT) post-somministration of ChAdOx1 nCoV-19 vaccine. Recent studies have shown structural similarities between heparin and β2GPI, which may be responsible for thrombotic events in those infected with SARS-Cov-2 and VITT, who never had heparin. In particular, oxidised-β2GPI (β2GPIox) may mimic heparin by structural analogy and link to PF4. Considering the structural similarities between heparin and β2GPIox, and demonstrating the immunogenicity of the hypothesised complex in APS, the alternative molecule could be represented by β2GPIox itself, thus explaining the thrombotic events following vaccination in subjects who have never received heparin. The aim of the study is to test the potential immunogenicity of the β2GPIox-PF4 complex and the presence of antibodies against this complex in patients with aPS, thrombosis during infection with SARS-CoV-2 or VITT. 34 patients with proven diagnosis of APS, 17 patients with thrombosis related to infection SARS CoV-2 and 3 patients with VITT were enrolled. Only one aPS patient received heparin prior to testing. Antibodies to the β2GPIox-PF4 complex were evaluated by home made ELISA immunoenzyme testing. Competitive inhibition (homologous) experiments of the bond of PF4 with β2GPIox in the fluid phase were conducted in order to verify the binding specificity. Anti-β2GPIox-PF4 antibodies were detected in 11 of 34 aPS patients (32%) and all VITT patients (100%), while none of covid-19 patients tested positive. In addition, Anti-β2GPIox-PF4 antibodies positivity significantly correlated with the presence of anti-β2GPI antibodies (p=0.0259) and with a triple positive antibody profile (p=0.0017) (Figure 1). There was no significant association between anti-β2GPIox-PF4 antibodies' title and clinical features of aPS patients. The results of this study show a new antibody positivity in aPS and VITT. In particular we have identified a high prevalence of anti-β2GPIox-PF4 antibodies which may be involved in the pathophysiology of both aPS and VITT. In addition the absence of anti-β2GPIox-PF4 antibodies in covid-19 patients suggest that the thrombotic mechanism that underlies VITT is different from covid-19 and, on the contrary, could resemble aPS. [1]Alessandri C et al. New autoantigens in the antiphospholipidsyndrome. Autoimmun Rev. 2011 [2]Sikara MP et al. {beta}2 Glycoprotein I ({beta}2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood. 2010 Jan 21 [3] Favaloro EJ et al. Antibodies against Platelet Factor 4 and Their Associated Pathologies: From HIT/HITT to Spontaneous HIT-Like Syndrome, to COVID-19, to VITT/TTS. Antibodies (Basel). 2022 Jan 21 NIL. None Declared. [Display omitted]

Traditional agroecosystems are considered as main conservatories of landraces biodiversity because they preserve their dynamic processes and farmers’ knowledge of selection and management inherent in the development of local cultivars. The Mediterranean region still harbours traditional agroecosystems of particular importance for preserving crop biodiversity, being sweet chestnut ( Castanea sativa Miller) a good example. This is one of the multipurpose species of most economic importance in the Mediterranean basin, cultivated extensively for fruit production, and the majority of varieties are the result of the selection of landraces by farmers. In this study, a set of European chestnut traditional varieties were evaluated in order to characterise its genetic resources and detect a possible response in the adaptive potential of this germplasm. Results of Bayesian analysis revealed a clear structure among cultivars from Italy and Spain with a low degree of admixture between them. Furthermore, a strong structure was detected within germplasm from each country congruent with their geographic origin. Statistical analyses did not reveal any significant marker deviating from neutral expectations. Results were discussed considering previous studies carried out on neutral and morphological markers, concluding that information provided by different markers was more powerful in detecting the maximum amount of genetic variation in chestnut varieties, and establishing a baseline to continue identifying markers underlying phenotypic differentiation and/or response to environmental cues among varieties.

The extremely high sensitivity to the external environment and the high specific surface area, as well as the absence of bulk phenomena that could interfere with the response signal, make graphene highly attractive for the applications in the field of sensing. Among the various methods for producing graphene over large areas, liquid phase exfoliation (LPE) appears to be very promising, especially if combined with inkjet printing (IJP), which offers several advantages, including the selective and controlled deposition of small ink volumes and the versatility of the exploitable inks and substrates. Herein we present a feasibility study of chemiresistive gas sensors inkjet-printed onto paper substrates, in which a LPE graphene suspension dispersed in a water/isopropanol (H2O/IPA) mixture is used as sensing ink. The device performances, in terms of relative conductance variations, upon exposure to NO2 at standard ambient temperature and pressure, are analysed. In addition, we examine the effect of the substrate morphology and, more specifically, of the ink/substrate interaction on the device performances, by comparing the response of different chemiresistors fabricated by dispensing the same suspension also onto Al2O3 and Si/SiO2 substrates and carrying out a supportive atomic force microscopy analysis. The results prove the possibility to produce sensor devices by means of a wholly environmentally friendly, low-cost process that meets the requests coming from the increasing field of paper-based electronics and paving the way towards a flexible, green-by-design mass production.

We provide a database of the surface ruptures produced by the 26 December 2018 Mw 4.9 earthquake that struck the eastern flank of Mt. Etna volcano in Sicily (southern Italy). Despite its relatively small magnitude, this shallow earthquake caused about 8 km of surface faulting, along the trace of the NNW-trending active Fiandaca Fault. Detailed field surveys have been performed in the epicentral area to map the ruptures and to characterize their kinematics. The surface ruptures show a dominant right-oblique sense of displacement with an average slip of about 0.09 m and a maximum value of 0.35 m. We have parsed and organized all observations in a concise database, with 932 homogeneous georeferenced records. The Fiandaca Fault is part of the complex active Timpe faults system affecting the eastern flank of Etna, and its seismic history indicates a prominent surface-faulting potential. Therefore, this database is essential for unravelling the seismotectonics of shallow earthquakes in volcanic areas, and contributes updating empirical scaling regressions that relate magnitude and extent of surface faulting. Measurement(s) coseismic surface rupture • surface rupture kinematics • surface rupture displacement • surface rupture location Technology Type(s) field survey • GPS navigation system Factor Type(s) offset • strike • angle • length • latitude • longitude • elevation Sample Characteristic - Environment volcanic field Sample Characteristic - Location Island of Sicily • Mount Etna Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.11673027

We provide a database of the surface ruptures produced by the 26 December 2018 Mw 4.9 earthquake that struck the eastern flank of Mt. Etna volcano in Sicily (southern Italy). Despite its relatively small magnitude, this shallow earthquake caused about 8 km of surface faulting, along the trace of the NNW-trending active Fiandaca Fault. Detailed field surveys have been performed in the epicentral area to map the ruptures and to characterize their kinematics. The surface ruptures show a dominant right-oblique sense of displacement with an average slip of about 0.09 m and a maximum value of 0.35 m. We have parsed and organized all observations in a concise database, with 932 homogeneous georeferenced records. The Fiandaca Fault is part of the complex active Timpe faults system affecting the eastern flank of Etna, and its seismic history indicates a prominent surface-faulting potential. Therefore, this database is essential for unravelling the seismotectonics of shallow earthquakes in volcanic areas, and contributes updating empirical scaling regressions that relate magnitude and extent of surface faulting.

A genetic linkage map of European chestnut (Castanea sativa Mill.) based on RAPD, ISSR and isozyme markers was constructed using the two-way pseudo-testcross strategy. A total of 96 individuals from a F^sub 1^ full-sib family was genotyped with 381 molecular markers (311 RAPDs, 65 ISSRs, 5 isozymes). Markers in testcross configuration, segregating 1:1, were used to establish two separate maternal and paternal maps including 187 and 148 markers, respectively. The markers identified 12 linkage groups based on the haploid number of chestnut. The female and male framework maps reached a total length of 720 and 721 cM (Kosambi), respectively, representing a 76% and 68% coverage of the overall genome. A total of 46 markers, found in intercross configuration, segregating 3:1 and 1:2:1, were used to identify homologous linkage groups between parental maps; out of 12 linkage groups 11 could be joined. RAPD and ISSR markers showed a good and comparable reliability, allowing for the first time the establishment of a saturated linkage map for European chestnut. These maps will be a starting point for studies on the structure, evolution and function of the chestnut genome. Identification of QTLs for adaptive traits in chestnut will be the primary target.[PUBLICATION ABSTRACT]

We present a new 1:25,000-scale geological map of the Middle Aterno Valley basin, the epicenter of the 2009 L'Aquila M W 6.1 earthquake. This earthquake highlighted the incomplete understanding of the geology of the area, in particular the Quaternary continental deposits and active tectonics, which caused the Paganica fault system to be ignored by researchers. The map, utilizing airborne LiDAR analysis and traditional field survey approaches, is the first example in Italy (and one of the few in Europe) that integrates high-resolution topography in active tectonic studies. With unprecedented detail and precision on the spatial distribution of deposits, the map of the geomorphic and tectonic features provides new insight for the reconstruction of the Quaternary basin evolution and estimation of long-term deformation rates for the the Paganica fault system. Detailed fault mapping of Quaternary deposits represents an essential input for seismic hazard assessment and surface faulting hazard evaluation.

Simple sequence repeat (SSR) markers from Quercus and Castanea were used for comparative mapping between Quercus robur (L.) and Castanea sativa (Mill.). We tested the transferability of SSRs developed in Quercus to Castanea and vice-versa. In total, 47% (25) of the Quercus SSRs and 63% (19) of the Castanea SSRs showed a strong amplification product in the non-source species. From these 44 putative comparative anchor tags, 19 (15 from Quercus and 4 from Castanea) were integrated in two previously established genetic linkage maps for the two genera. SSR loci were sequenced to confirm the orthology of the markers. The combined information from both genetic mapping and sequence analysis were used to determine the homeology between seven linkage groups, aligned on the basis of pairs or triplets of common markers, while two additional groups were matched using a single microsatellite marker. Orthologous loci identified between Q. robur and C. sativa will be useful as anchor loci for comparative mapping studies within the Fagaceae family.

Background Over the past few years, treatment of burn scars with lipofilling has shown encouraging clinical results in terms of texture, color, softness, and quality of skin patterns. This clinical application has been widened to include treatment for scars resulting from surgical correction of cicatricial ectropion. In fact, although standard surgery with flaps and skin grafts can grant significant functional and cosmetic improvements, these often are not complete because of secondary surgical scars. Methods The case of a 43-year-old man with cicatricial outcomes from chemical burns and subsequent surgical repair of medial ectropion in the lower eyelid is reported. The scar area was treated with injection of adipose tissue harvested from abdominal subcutaneous fat and processed according to Coleman’s technique. Results At the 1-year follow-up assessment after lipostructure, the patient no longer reported xeroftalmia and epiphora. He had experienced complete functional recovery with excellent cosmetic results. Conclusions Lipostructure of cicatricial ectropion seems to complete and improve the results of the standard surgical approach, and its long-lasting benefits are in keeping with the theoretical basis of this procedure.