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Background Tibialis anterior (TA) tendinosis is rarely reported on in the literature. It is seen in patients older than 45 and causes weakness in dorsiflexion. This paper aims to describe surgical treatment and clinical outcomes. Methods Between 2015 and 2018, nine patients (six females, three males) with severe TA tendinosis with no tear (2), partial (1), or complete (6) underwent operative treatment. Patients underwent debridement and direct repair without augmentation, direct repair with fiber tape augmentation, tibialis posterior tendon (PTT) transfer, or tibialis anterior tendon (TAT) augmentation with a tendon autograft (n = 4). Autografts consisted of extensor digitalis longus (EDL) tendon, plantaris tendon, or both. Results Mean postoperative follow-up was 21.3 (range 8–31) months. All patients had a concomitant gastrocnemius recession, and three had hindfoot arthrodesis. Preoperative dorsiflexion strength was 0/5 for all and improved to 5/5 postoperatively in seven. The only current smoker developed wound dehiscence 2 weeks postoperatively and healed by 4. One developed marginal skin necrosis 3 weeks postoperatively and was treated successfully with casting. Conclusion Surgery reestablished function in individuals with TA tendinosis and allowed high level of satisfaction. Direct repair is possible. If the tendon gap is too large an autograft of EDL and plantaris tendon can be utilized. Level of evidence: Level III Retrospective Comparative Study

Chronic myeloid leukemia (CML) is caused by BCRABL1 in a cell with the biological potential, intrinsic or acquired, to cause leukemia. This cell is commonly termed the CML leukemia stem cell (LSC). In humans a CML LSC is operationally-defined by ≥1 in vitro or in vivo assays of human leukemia cells transferred to immune-deficient mice. Results of these assays are sometimes discordant. There is also the unproved assumption that biological features of a CML LSC are stable. These considerations make accurate and precise identification of a CML LSC difficult or impossible. In this review, we consider biological features of CML LSCs defined by these assays. We also consider whether CML LSCs are susceptible to targeting by tyrosine kinase inhibitors (TKIs) and other drugs, and whether elimination of CML LSCs is needed to achieve therapy-free remission or cure CML.

The shallow landslides assessment is a hard task in territories featuring composite influence of natural and anthropic factors. In Liguria region (northwestern Italy), the landscape presents widespread human intervention prevalently represented by terraces. The assessment of predisposing factors in such landscape deserve a multidisciplinary approach. We implemented a classification methodology based on the Analytical Hierarchy Process. In GIS environment we overlaid several layers: (i) slope, (ii) land use, (iii) lithology, and (iv) aspect. Slope and aspect have been computed on a filtered (based on TPI) high-resolution DTM with the removal of terraces, in order to obtain the pristine slope pattern. Each spatial data was then reclassified according to the weighting procedures thus producing a landslide susceptibility map. This methodology represents a starting point for the correct assessment of shallow landslides occurrence, capable to generate a map, taking in account of the peculiar features of this extremely man-made territory.

Hyperextension-distraction type injury of the thoracolumbar spine is an unstable fracture pattern that generally necessitates surgical stabilization by posterior instrumentation. Care must be taken when positioning these patients from supine to prone due to the unstable nature of their injury. The study objectives were (1) to describe a novel modification of the Jackson table turn technique, which may be safer and more effective than the conventional log-roll method and traditional Jackson table technique for positioning patients with hyperextension-distraction injuries of the thoracolumbar spine from supine to prone in the operating room and (2) to present two cases in which this technique was successfully performed. Two patients were carefully positioned from supine to prone by our modification of the Jackson table turn technique, which utilizes a Wilson frame sandwiched between two flat-top Jackson frames. Case 1: a 65-year-old female presented status-post motor vehicle collision with a T9–T10 extension-distraction injury, requiring T7–T12 posterior spinal instrumented fusion (PSIF). Case 2: a 72-year-old female presented status-post motor vehicle collision with a T9–T10 extension-distraction injury and an unstable L1 burst fracture, requiring T7–L2 PSIF. Both patients remained hemodynamically stable and neurologically intact throughout positioning and postoperatively. This technique is safe and effective for positioning patients with hyperextension-distraction type injuries of the thoracolumbar spine from supine to prone in the operating room and may be superior to conventional methods. These slides can be retrieved under Electronic Supplementary Material.

Prende l’avvio, con questo fascicolo, DIDIT. Didattica dell’italiano. Studi applicati di lingua e letteratura, una nuova rivista scientifica nata dalla collaborazione tra il Centro competenze didattica dell’italiano lingua di scolarizzazione del Dipartimento formazione e apprendimento della Scuola universitaria professionale della Svizzera italiana e l’Alta scuola pedagogica dei Grigioni. Alla rivista partecipano quindi due istituzioni universitarie che si occupano della formazione degli insegnanti del Ticino e dei Grigioni, i due cantoni svizzeri in cui l’italiano è lingua ufficiale (nei Grigioni accanto al tedesco e al romancio): un contesto del tutto particolare, che vede l’italiano insieme lingua di scolarizzazione e lingua prima (in Ticino e nel Grigioni italiano), lingua seconda (in Ticino) e lingua straniera nella scuola dell’obbligo (nella parte tedesca del Canton Grigioni). In una realtà così peculiare dal punto di vista linguistico e culturale, DIDIT intende offrire uno strumento di ricerca e aggiornamento rivolto a chi opera, per ragioni di studio o di lavoro, nell’ambito della didattica dell’italiano come lingua prima, come lingua seconda o come lingua straniera. Vista la particolare situazione linguistica del Canton Grigioni, del limitrofo Alto Adige e tenuto conto delle diverse altre lingue presenti sul territorio grigionese e ticinese accanto alle lingue ufficiali, la nuova rivista prende in considerazione anche la ricerca sulla didattica del plurilinguismo. In questo senso la rivista si presenta come luogo di scambio scientifico privilegiato e unico nel panorama delle pubblicazioni scientifiche presenti sul territorio nazionale svizzero e come uno dei pochi strumenti a livello internazionale che prendono in esame l’italiano nei diversi contesti di insegnamento; l’obiettivo sul medio-lungo termine è di configurarsi come un punto di riferimento nel campo degli studi sulla didattica dell’italiano e del plurilinguismo, caratterizzati dal costante connubio tra dimensione teorica e dimensione applicativa. DIDIT è divisa in tre sezioni: Studi e ricerche, Esperienze didattiche e Recensioni e segnalazioni. La prima, affidata alla penna di studiose e studiosi di chiara fama nel settore della didattica della lingua e della letteratura italiana (in questo primo numero Maria G. Lo Duca e Giuliana Fiorentino e, per la tematica del plurilinguismo, Ruth Videsott), accoglie approfondimenti teorici su temi afferenti agli ambiti didattici sopra ricordati. La seconda è dedicata a esempi di applicazioni e percorsi didattici, affidati a studiose e studiosi, ricercatrici e ricercatori, docenti attive e attivi nella scuola di ogni ordine e grado (in questo numero Livia Radici Tavernese, Daniele Dell’Agnola, Stefania Crameri e Daniela Kappler). La terza presenta, infine, recensioni di libri e studi che possono contribuire all’innovazione didattica nelle discipline di riferimento e a segnalazioni di opere – come albi illustrati, poesie, raccolte di racconti e romanzi – rivolte a lettori di diverse fasce di età. Tenuto conto dei contesti minoritari con cui si vede confrontato l’italiano in Svizzera, la rivista ambisce a diventare anche uno strumento per il sostegno e la promozione della lingua italiana in questo contesto nazionale, e non solo. In tal senso, si propone di estendere il proprio orizzonte agli studi sulla didattica dell’italiano in un’accezione ampia, che accolga prospettive plurali e sguardi capaci di spaziare dalla teoria all’applicazione pratica, avendo sempre come obiettivo di fondo un aggiornamento costante sulle strategie, sui metodi, sulle ricerche volte a migliorare e a innovare l’insegnamento dell’italiano. In tal modo la rivista garantisce lo scambio e la comunicazione tra il mondo della ricerca e quello della scuola, a livello nazionale e internazionale: attraverso la scelta dei temi, degli ambiti di ricerca e di riflessione, DIDIT vuole così rispondere alle sfide didattiche e teoriche poste alla disciplina e stimolare il dibattito scientifico e pubblico.

[EN] At present, there are certain generic abilities which are considered to be as important as professional abilities to perform properly at work. Among these abilities, we can mention the ability to communicate in the oral and written medium, to interact and work in teams, to evaluate others and evaluate themselves, to act in new situations, to take decisions, to search common goals and to commit to their sociocultural environment. The present study aimed to find out about the abilities in oral communication of undergraduate students of elective subjects in the programme of the Veterinary Medicine course at Universidad Nacional del Litoral. These abilities were explored by means of an online survey administered to these students. The survey was designed around different dimensions related to abilities in oral communication: the purpose of communication, the bilateral nature of the communicative process, being an empathic communicator, active listening, the combination of verbal and non-verbal abilities and strategic oral communication in formal situations. Our results showed that in general the students perceive that their abilities in relation to most dimensions are satisfactory. However, a significant number of them expressed that they have certain problems with strategic oral communication in formal situations. This study reveals the importance of conducting classroom interventions oriented towards the development and improvement of abilities in strategic oral communication in order to contribute to meet the demands of the professional world., [ES] En la actualidad, existen ciertas competencias genéricas que son consideradas tan importantes para el buen desempeño laboral como las competencias profesionales. Entre ellas se encuentran la capacidad de comunicación oral y escrita, de interactuar y trabajar en equipo, de crítica y autocrítica, de actuar en nuevas situaciones, de tomar decisiones, de motivar y conducir hacia metas comunes y de comprometerse con el medio socio-cultural. El presente estudio tuvo como objetivo conocer las competencias para la comunicación oral de los estudiantes de las asignaturas electivas de la carrera Medicina Veterinaria en la Universidad Nacional del Litoral. Se exploró acerca de estas competencias mediante una encuesta en línea administrada a dichos estudiantes. La misma fue diseñada en torno a distintas dimensiones relacionadas con las competencias para la comunicación oral: el propósito de la comunicación, el sentido bilateral o de intercambio del proceso comunicativo, la empatía del comunicador, el proceso de adaptación en la comunicación, la escucha activa, la combinación de habilidades de comunicación verbal y no verbal, y la comunicación oral estratégica en situaciones formales. Los resultados obtenidos revelaron que en términos generales los estudiantes perciben que las mismas son satisfactorias, aunque un número significativo manifestó tener ciertas dificultades en relación con la comunicación oral estratégica en situaciones formales. Esta investigación pone de manifiesto la importancia de realizar intervenciones didácticas afines al desarrollo y mejoramiento de competencias para la comunicación oral que contribuyan a cumplimentar con las exigencias de la futura actividad profesional de nuestros estudiantes.

The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar’s phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).

Introduction FLT3 receptor gene has been reported to be mutated in about 30% of AML, with two different kinds of mutations identified: in-frame duplications within the juxtamembrane region (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD). In term of prognosis, the proper role of these mutations is still debated. Moreover, FLT3 mutations are often subjected to clonal evolution, thus how to properly monitor FLT3 mutated clones, evaluate minimal residual disease, manage FLT3 inhibitors (FLT3i) are only some of the open issues. FLAM is an observational study involving FLT3 positive AMLs to gain clinical and molecular data useful to ameliorate real-life physicians' management of this disease. Here we report the results of a preliminary analysis of the retrospective phase of the study. Methods The retrospective phase of FLAM multi-center observational study enrolled each AML patient treated in 33 participating Italian centers detected to carry a FLT3 mutation since 2012. Clinical and molecular data were collected in accordance with GCP and Helsinki declaration in electronic case report forms. Results At data cut-off , 1st of July 2020, 289 patients with FLT3 mutation at diagnosis were enrolled in the retrospective phase of FLAM study, being evaluable in this analysis, with a median age at diagnosis of 62 years (min-max: 18-94) and a M:F ratio of 141/148 (Patients' characteristics are summarized in table 1). 29 out 289 (10 %) patients had a low risk AML, 190/289 (65,7 %) had an intermediate risk AML and 27/289 (9,3 %) patients had a high risk AML, according to ELN 2017 risk stratification or ELN 2010 in case of allelic ratio unavailability (43 patients had no available ELN risk at baseline). A more frequent association between FLT3-ITD and normal karyotype and between FLT3-TKD mutation and other cytogenetic alterations not conferring a favorable/adverse risk has been observed (p = 0.045). Among the study population, 255/289 (88 %) patients carried a FLT3-ITD, 32/289 (11 %) a FLT3-TKD point mutation and 2/289 (1 %) patients both mutations. Capillary electrophoresis has been the technical method used to investigate FLT3-ITD in 163 of 226 (72 %) patients with information on the method used, while Sanger Sequencing in 47 out of 226 (21 %) patients and Next generation sequencing (NGS) in 16 out of 226 (7 %) patients. Overall, NGS has been adopted to investigate FLT3 gene status in 18 out of 259 patients (7 %). FLT3-ITD allelic ratio was available in 62 of 257 (24 %) ITD patients and was greater than or equal to 0.5 in 35/62 (56 %) patients. During patients' follow-up, 19/289 (7 %) patients affected by a FLT3 positive AML at diagnosis underwent a disease clonal evolution with a FLT3 negative AML progression or relapse. Regarding treatment options in FLT3-AML, in our cohort FLT3i were administered as first-line of therapy in only 36/289 (13 %) patients, always in a combination, of which in 26/36 (72.2 %) with intensive chemotherapy. As expected, intensive chemotherapy represented the induction regimen in the majority of the patients (211/289, 73 %). On the other hand, FLT3i were administered as rescue therapy in 62/171 (36 %) cases (47/62 single-agent and in 15/62 in combination) and as re-induction therapy in 22/80 (28 %) cases (10/22 single-agent and 12/22 in combination). Overall, a FLT3i has been administered as single-agent 81 times, of which Gilteritinib was the most frequently used (56/81, 69,1 %), followed by quizartinib (18/81, 22,2 %). Among the 52 documented combinations of a FLT3i with other drugs, particularly noteworthy is the administration of Sorafenib, in 20/52 (39 %) cases in this real-life study. Lastly, nine out of 289 (3 %) patients received a FLT3i as maintenance therapy after HSCT. Data regarding the correlation among the different regimens, with a special focus on FLT3i, other molecular features and response/survival are currently under analysis. Conclusions These data coming from a preliminary analysis portray the state of a large multi-center retrospective cohort of FLT3-positive AML patients treated in Italy between 2012 and 2020, including interesting insights regarding technical methods used to characterize the disease and the therapeutic scenario in which FLT3 inhibitors have been developed. Further safety and effectiveness data may reveal beneficial to ameliorate physicians' real-life clinical practice. Acknowledgements: work supported by Daiichi-Sankyo. Download : Download high-res image (459KB) Download : Download full-size image Disclosures Martelli: Amgen: Membership on an entity’s Board of Directors or advisory committees; AbbVie: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Rigolin: Abbvie: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fracchiolla: Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau; ABBVIE: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau. Bocchia: Incyte: Honoraria; CELGENE: Honoraria. Todisco: Jannsen, Abbvie, Jazz: Membership on an entity’s Board of Directors or advisory committees. Papayannidis: Abbvie, Janssen, Novartis, Amgen, Pfizer: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties. OffLabel Disclosure: Sorafenib is a registered drug for the treatment of hepatocellular carcinoma. Due to its multi-targeted tirosine kinase inhibitor effect it demonstrated efficacy in FLT3-AML when administered as an off-label prescription.

Simple Summary Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors. CML LSCs have many features in common with hematopoietic stem cells (HSCs) and selectively targeting this population and sparing HSCs is of paramount importance. Targeted therapy by liposome via reducing side effects, controlled release, and versatile surface modifications is an effective way for the treatment of different cancers including leukemia. Here for the first time, we designed a liposome conjugated with Begelomab (anti-CD26) loaded with venetoclax to selectively target CD26+ CML LSCs/progenitor cells and to increase treatment outcome in CML patients. We proved that after antigen binding and drug release, the CD26+ LSCs/progenitor cells could be eliminated without any side effect on CD26− cells. Abstract CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.

Landslide inventories provide the knowledge basis for many geomorphological applications and also planning and emergency management. Detailed landslide inventories should also be prepared where pre-existing inventories are available, as knowledge updates. In this paper, we present a new geomorphological landslide inventory for an area of the High Agri Valley, Southern Italian Apennines. The map was prepared through systematic interpretation of historical aerial photographs testing extensive use of anaglyph glasses in StereoPhoto Maker freeware. A total of 2124 landslides were classified based on the type of movement, estimated depth, estimated relative age and three levels of uncertainty, providing landslide attributes and map constraints useful for land planning and hazard studies. The map also documents the relationships between landslides and fluvial landforms of different generations, recording important information to investigate the geomorphological evolution of the area further. We expect that landslide mapping in similar environments will benefit from the workflow here presented.

Dihydroorotate Dehydrogenase (DHODH) is a key enzyme of the de novo pyrimidine biosynthesis, whose inhibition can induce differentiation and apoptosis in acute myeloid leukemia (AML). DHODH inhibitors had shown promising in vitro and in vivo activity on solid tumors, but their effectiveness was not confirmed in clinical trials, probably because cancer cells exploited the pyrimidine salvage pathway to survive. Here, we investigated the antileukemic activity of MEDS433, the DHODH inhibitor developed by our group, against AML. Learning from previous failures, we mimicked human conditions (performing experiments in the presence of physiological uridine plasma levels) and looked for synergic combinations to boost apoptosis, including classical antileukemic drugs and dipyridamole, a blocker of the pyrimidine salvage pathway. MEDS433 induced apoptosis in multiple AML cell lines, not only as a consequence of differentiation, but also directly. Its combination with antileukemic agents further increased the apoptotic rate, but when experiments were performed in the presence of physiological uridine concentrations, results were less impressive. Conversely, the combination of MEDS433 with dipyridamole induced metabolic lethality and differentiation in all AML cell lines, this extraordinary synergism was confirmed on AML primary cells with different genetic backgrounds and was unaffected by physiological uridine concentrations, predicting in human activity.

BackgroundDihydroorotate Dehydrogenase (DHODH) is a key enzyme of the de novo pyrimidine biosynthesis, whose inhibition was recently found to induce differentiation and apoptosis in acute myeloid leukemia (AML). DHODH inhibitors were previously investigated in solid tumors, where they showed promising antiproliferative activity, both in vitro and in vivo. However, their effectiveness was not confirmed in clinical trials, probably due to the pyrimidine salvage pathway that cancer cells could exploit to survive. In this study we investigated the pro-apoptotic activity of MEDS433, the DHODH inhibitor developed by our group, against AML. Learning from previous failures, we challenged our model mimicking in vivo conditions, and looked for synergic combination to boost apoptosis.MethodsWe evaluated the apoptotic rate of multiple AML cell lines and AML primary cells treated with MEDS433 or other DHODH inhibitors, alone and in combination with classical antileukemic drugs or with dipyridamole, a blocker of the pyrimidine salvage pathway. Experiments were also performed mimicking in vivo conditions, i.e., in the presence of physiological uridine plasma levels (5 μM).ResultsMEDS433 showed a strong apoptotic effect against multiple AML cell lines, which was at least partially independent from the differentiation process. Its combination with classical antileukemic agents resulted in a further increase of the apoptotic rate. However, when MEDS433 was tested in the presence of 5 μM uridine and/or in primary AML cells, results were less impressive. On the contrary, the combination of MEDS433 with dipyridamole resulted in an outstanding synergistic effect, with a dramatic increase of the apoptotic rate both in AML cell lines and AML primary cells, which was unaffected by physiological uridine concentrations. Preliminary analyses show that the toxicity of this treatment should be limited to proliferating cells.ConclusionsThe combination of a DHODH inhibitor and dipyridamole is characterized by differentiating and pro-apoptotic features and induces metabolic lethality on a wide variety of AMLs with different genetic backgrounds.

The Coronavirus Disease 2019 (COVID-19) pandemic is a global threat to healthcare systems, requiring hospitalization in sub intensive and intensive care for respiratory syndrome in 25-30% of patients and accounting for a lethality up to 15%.In this retrospective study the clinical characteristics of 215 COVID-19 patients were correlated with the peripheral blood immune status.Different groups of COVID-19 patients may be identified on the basis of clinical behavior and a strong correlation between groups and age and comorbidities as well as with the immune profile is demonstrated. A lower age correlates with a lower severity of the disease differentiating between patients who may be quarantined at home and those requiring hospitalization. An older age (>82 years) together with a higher number of comorbidities is associated to a very severe prognosis. The absolute number of CD3+, CD4+, CD8+ T lymphocytes was progressively decreasing according to the severity of the disease and a CD3+ and CD8+ threshold indicating very severe cases is suggested.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are distinct diagnostic disorders. However, they also frequently co-occur and may share a common etiology. It was proposed conceptually a neural network framework that explains differences and commonalities between DD and DCD through impairments of distinct or intertwined cortico-subcortical connectivity pathways. The present study addressed this issue by exploring intrinsic cortico-striatal and cortico-cerebellar functional connectivity in a large (n = 136) resting-state fMRI cohort study of 8–12-year-old children with typical development and with DD and/or DCD. We delineated a set of cortico-subcortical functional circuits believed to be associated with the brain’s main functions (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal control, and default-mode). Next, we assessed, using general linear and multiple kernel models, whether and which circuits distinguished between the groups. Findings revealed that somatomotor cortico-cerebellar and frontoparietal cortico-striatal circuits are affected in the presence of DCD, including abnormalities in cortico-cerebellar connections targeting motor-related regions and cortico-striatal connections mapping onto posterior parietal cortex. Thus, DCD but not DD may be considered as an impairment of cortico-subcortical functional circuits.

Nowadays, the increasing demand to collect, manage and share archives of data supporting geo-hydrological processes investigations requires the development of spatial data infrastructure able to store geospatial data and ground deformation measurements, also considering multisource and heterogeneous data. We exploited the GeoNetwork open-source software to simultaneously organize in-situ measurements and radar sensor observations, collected in the framework of the HAMMER project study areas, all located in high mountain regions distributed in the Alpines, Apennines, Pyrenees and Andes mountain chains, mainly focusing on active landslides. Taking advantage of this free and internationally recognized platform based on standard protocols, we present a valuable instrument to manage data and metadata, both in-situ surface measurements, typically acquired at local scale for short periods (e.g., during emergency), and satellite observations, usually exploited for regional scale analysis of surface displacement. Using a dedicated web-interface, all the results derived by instrumental acquisitions and by processing of remote sensing images can be queried, analyzed and downloaded from both expert users and stakeholders. This leads to a useful instrument able to share various information within the scientific community, including the opportunity of reprocessing the raw data for other purposes and in other contexts.

The NextData project (2012-2018) provided quantitative information on the current state and on past, present and future climate and environmental changes in Italian mountains. The multidisciplinary approach combined field monitoring, satellite observations, reconstruction of past climatic conditions in Italy for the last few thousand years, and numerical simulations on the expected climate and environmental variability in the Italian mountains for the next decades. The data, information and results obtained during the NextData project are open-access, and they are stored in a system of open thematic archives coordinated by a general web access to the project. This system is in keeping with the approach by the Group on Earth Observations (GEO), to which Italy strongly contributed also through the NextData project. The archives and databases are hosted in servers of public research institutions, ensuring continuity after the project completion and avoiding the risk of dispersing the collected information and the acquired knowledge.

Background One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold standard" graft choice but are limited in supply and impart significant patient morbidity. Xenograft bone is an attractive alternative from donors with controlled biology, in large supply and at a theoretically lower cost. Clinical results with xenograft bone for orthopedic applications have been mixed in the limited clinical trials published. Methods In the current review, we introduce fundamental principles of bone grafting, systematically review all orthopedic clinical studies reporting outcomes on patients transplanted with xenograft bone, and we present our own clinical results from patients grafted with bovine bone in foot and ankle reconstructive procedures. Results Thirty-one clinical studies were identified for review and the majority (47%) were from spine surgery literature. Favorable results were reported in 44% of studies while 47% of studies reported poor outcomes and discouraged use of xenograft bone products. In our own clinical series, xenograft failed to integrate with host bone in 58% of cases and persistent pain was reported in 83% of cases. Conclusions This is the first systematic review of clinical results reported after bone xenotransplantation for orthopaedic surgery applications. Current literature does not support the use of xenograft bone products and our institution's results are consistent with this conclusion. Our laboratory has reported promising pre-clinical results with a xenograft product derived from porcine cancellous bone, but additional testing is required before considering clinical translation.

Molecular estimates of the divergence of placental and marsupial mammals and their broader clades (Eutheria and Metatheria, respectively) fall primarily in the Jurassic period. Supporting these estimates, Juramaia-the oldest purported eutherian-is from the early Late Jurassic (160 million years ago) of northeastern China. Sinodelphys-the oldest purported metatherian-is from the same geographic area but is 35 million years younger, from the Jehol biota. Here we report a new Jehol eutherian, Ambolestes zhoui, with a nearly complete skeleton that preserves anatomical details that are unknown from contemporaneous mammals, including the ectotympanic and hyoid apparatus. This new fossil demonstrates that Sinodelphys is a eutherian, and that postcranial differences between Sinodelphys and the Jehol eutherian Eomaia-previously thought to indicate separate invasions of a scansorial niche by eutherians and metatherians-are instead variations among the early members of the placental lineage. The oldest known metatherians are now not from eastern Asia but are 110 million years old from western North America, which produces a 50-million-year ghost lineage for Metatheria.

Introduction: The outcome of patients with acute myeloid leukemia (AML) secondary to myelodisplastic syndrome (MDS) or therapy-related (t-AML) receiving conventional treatment and allogeneic stem cell transplantation consolidation (HSCT) is poor. CPX-351 is a new drug composed by liposomal encapsulated cytarabine and daunorubicin, at a fixed molecular ratio of 5:1. It showed superior results, compared to standard 3+7 induction, in a phase III trial (Lancet et al, JCO 2018) in patients affected by t-AML or AML with myelodisplasia-related changes and it is now commercially available for secondary AML (sAML). We recently published results from CPX-351 Italian Named (Compassionate) Use Program (CUP) which enrolled 73 elderly sAML patients (Guolo et al, Blood Cancer J. 2020) showing that CPX-351 is an effective induction regimen for high risk AML patients treated with a curative aim. With a limited follow up, our data suggested the good activity and tolerability of CPX-351. Good quality remissions with acceptable toxicity in the majority of patients was achieved and CPX-351 increased the feasibility of HSCT in a poor risk AML cohort. Scarce data are available on long term outcome of high risk patients receiving CPX-351 in the real life setting. Here we report the results from the extended follow up analysis of the Italian CUP. Results: Seventy three patients were enrolled between December 2018 and June 2019 in a compassionate use program (CUP) in 33 Italian Hematology Centers. Data collection began on July 2019 and included 71/73 patients (97.2%), enrolled in 31 Centers. As previously reported, median age was 65.5 years (52-79). Sixty-two (88%) patients had at least one relevant comorbidity upon enrollment. Six patients (9%) presented with ECOG 3-4 upon enrollment. With a median follow up of 22 months, median overall survival (OS) was 13 months (21.2 - 22.8 95% IC). Two-years OS was 28.6% in the whole cohort. In order to confirm the positive impact of HSCT in first complete remission (CR) and the correlation with the other variables, a landmark model was applied, including only patients alive and in CR at day 90. In landmark analysis, HSCT performed in first CR after CPX-351 was the only significant predictor of longer survival: median OS was not reached for patients transplanted in first CR Vs 12 months for patients who did not undergo HSCT, p < 0.05, Figure1). Two-year OS for patients who received HSCT was 57.6% vs 15.8% for patients who did not undergo HSCT. Conclusions: Results from the extended follow up of Italian CPX-351 CUP confirm the good activity CPX-351 in such a difficult cohort as sAML. Two-year OS for transplanted patients is high despite the high median age, the high frequency of severe comorbidities in this real life cohort of patients and the high frequency of high risk AML. On the contrary, non-transplanted patients show a poor outcome, thus confirming that CPX-351 induction as an optimal bridge to transplant induction therapy. Figure 1 Figure 1. Disclosures Galimberti: Incyte: Speakers Bureau; AbbVie, Janssen: Honoraria, Other: Travel grants. Marco: Insight,: Consultancy; Jazz: Consultancy; Janssen: Consultancy. Fracchiolla: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Speakers Bureau. Tafuri: Roche: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Rossi: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Pagano: Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy; Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau.