Search

Summary: Background: Acute myeloid leukaemia (AML) is a bone marrow malignancy with poor prognosis. One of several treatments for AML is midostaurin combined with intensive chemotherapy (MIC), currently approved for FLT3 mutation-positive (FLT3-MP) AML. However, many patients carrying FLT3 mutations are refractory or experience an early relapse following MIC treatment, and might benefit more from receiving a different treatment. Development of a stratification method that outperforms FLT3 mutational status in predicting MIC response would thus benefit a large number of patients. Methods: We employed mass spectrometry phosphoproteomics to analyse 71 diagnosis samples of 47 patients with FLT3-MP AML who subsequently received MIC. We then used machine learning to identify biomarkers of response to MIC, and validated the resulting predictive model in two independent validation cohorts (n = 20). Findings: We identified three distinct phosphoproteomic AML subtypes amongst long-term survivors. The subtypes showed similar duration of MIC response, but different modulation of AML-implicated pathways, and exhibited distinct, highly-predictive biomarkers of MIC response. Using these biomarkers, we built a phosphoproteomics-based predictive model of MIC response, which we called MPhos. When applied to two retrospective real-world patient test cohorts (n = 20), MPhos predicted MIC response with 83% sensitivity and 100% specificity (log-rank p

The biochemical valorization potential of food waste (FW) could be exploited by extracting decreasing added-value bio-based products and converting the final residues into energy. In this context, multi-purpose and versatile schemes integrating thermal and biochemical conversion processes will play a key role. An upstream thermal pretreatment + solid-liquid separation unit was here proposed to optimize the conversion of the liquid fraction of FW into valuable chemicals through semi-continuous fermentation process, and the conversion of the residual solid fraction into biomethane through anaerobic digestion. The solid residues obtained after thermal pretreatment presented a higher soluble COD fraction, which resulted in higher methane production with respect to the raw residues (0.33 vs. 0.29 Nm3CH4 kg-1VSfed) and higher risk of acidification and failure of methanogenesis when operating at lower HRT (20d). On the contrary, at HRT = 40 d, the pretreatment did not affect the methane conversion rates and both tests evidenced similar methane productions of 0.33 Nm3CH4 kg-1VSfed. In the reactor fed with pretreated residue, the association of hydrogenotrophic methanogens with syntrophic bacteria prevented the acidification of the system. Modelling proved the eligibility of the FW solid residues as substrates for anaerobic digestion, given their small inert fractions that ranged between 0% and 30% of the total COD content.

Abstract Resistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death.

There is a great number of medical conditions causing loss of tissue affecting upper lip, nasal base, columella and membranous septum; in our case wide resection of a relapsing squamous cell carcinoma required a challenging reconstruction to preserve function and aesthetics, guaranteeing oncological safety. We propose a modification of classical nasocheek advancement flap, avoiding alar lobule detachment in order to minimize the risk of nasal deformity. Concomitant cartilage graft reconstruction was contraindicated, since the need of adjuvant radiotherapy should not be excluded preoperatively. A single-stage and « single-technique » reconstruction is reported with good functional results and minimal cosmetic deformity at three months post-surgery.

El objetivo de este artículo es realizar un análisis cua-litativo y cuantitativo de una campaña de compras de calcos escultóricos en yeso llevada a cabo por Eduardo Schiaffino, director del Museo Nacional de Bellas Artes de Buenos Aires, entre 1903 y 1906. Por un lado, se in-vestigan los argumentos que se esgrimieron para justi-ficar la aprobación de un presupuesto de compras. Por otra parte, la conformación de una colección de yesos estuvo fuertemente informada por un circuito mercan-til guiado por una dinámica de oferta y demanda, dada la existencia de talleres estatales y privados internacio-nales que proveían yesos a precios accesibles y con una variada disponibilidad. A través de la sistematización de listas tentativas de compras y facturas se establece como hipótesis que Schiaffino se inscribió en un circuito comercial institucionalizado en paralelo a procurar obte-ner calcos con marcas de autoría.

Una de las acepciones de galería es la de un recinto para la exposición de obras de arte. Una obra de arte es una creación, en tanto propuesta estética, contenida de un discurso y estilo que hace uso de los materiales que le son propios; por ejemplo, la pintura o la escultura. En esta oportunidad la sección Galería de Mayéutica revista científica de humanidades y artes quiere contener, como parte del homenaje a la figura de Juan Francisco Sans, aquella que de forma sistemática se permitió realizar en el ámbito de la musicología y que resulta vasta por demás. Su utilidad y relevancia la convierte en un referente imposible de eludir y, quizás, "todos los caminos" conduzcan a ella. Este aporte, actualizado, fue cedido amablemente por su cónyuge, Mariantonia Palacios. Ha sido concebida en tres espacios; a saber: Sala1: In memoriam; Sala 2: Biografía y Sala 3: La elegancia de un legado.

Microbial chain elongation has emerged as a valuable bioprocess for obtaining marketable products, such as medium chain fatty acids usable in several industrial applications, from organic waste. The understanding of the microbiology and microbial ecology in these systems is crucial to apply these microbiomes in reliable production processes controlling microbial pathways to promote favourable metabolic processes, which will in turn increase product specificity and yields. In this research, the dynamics, cooperation/competition and potentialities of bacterial communities involved in the long-term lactate-based chain elongation process from food waste extract were evaluated under different operating conditions by DNA/RNA amplicon sequencing and functional profile prediction. The feeding strategies and the applied organic loading rates strongly affected the microbial community composition. The use of food waste extract promoted the selection of primary fermenters (i.e., Olsenella, Lactobacillus) responsible for the in situ production of electron donors (i.e., lactate). The discontinuous feeding and the organic loading rate 15 gCOD L-1 d-1 selected the best performing microbiome in which microbes coexist and cooperate to complete the chain elongation process. Both at DNA and RNA level, this microbiome was composed by the lactate producer Olsenella, the short chain fatty acids producers Anaerostipes, Clostridium sensu stricto 7, C. sensu stricto 12, Corynebacterium, Erysipelotrichaceae UCG-004, F0332, Leuconostoc, and the chain elongator Caproiciproducens. This microbiome also showed the highest predicted abundance of short-chain acyl-CoA dehydrogenase, the functional enzyme responsible for the chain elongation process. The combined approach herein used allowed to study the microbial ecology of chain elongation process from food waste by identifying the main functional groups, establishing the presence of potential biotic interactions within the microbiomes, and predicting metabolic potentialities. This study provided pivotal indications for the selection of high-performance microbiome involved in caproate production from food waste that can serve as a basis for further improving system performance and engineering the process scale-up.

Introduction There is evidence, although limited, that the Italian population has been no longer following a Mediterranean dietary pattern. The ARIANNA (Adherence to the Mediterranean Diet in Italy) project consists of a survey-based cross-sectional study with the objective of gaining a greater knowledge of adherence to the Mediterranean Diet and its main determinants in different age groups of the Italian population.Methods/analysis The ARIANNA study will involve males and females aged ≥7 years, born and resident in Italy, and proficient in Italian. The voluntary enrolment will be in the period between March 2023 and May 2023. The data, which will include sociodemographic factors and dietary habits, will be collected through a web-based questionnaire. Adherence to the Mediterranean Diet will be assessed through the use of two validated score systems: the Mediterranean Diet Quality Index in children and adolescents for participants aged ≤16 years and the Mediterranean Diet Serving Score for participants aged ≥17 years. A review of the scientific literature will be carried out to collect historical data on adherence to the Mediterranean dietary pattern in the Italian population, which will be compared with those collected within this project.Ethics and dissemination The ARIANNA study has been approved by the Ethics Committee of Istituto Superiore di Sanità. The results will be disseminated through peer-reviewed papers, leaflets and documents for the general public. A report will be presented to the national policy makers, to give them the tools to implement appropriate intervention to improve, in necessary, the adherence to Mediterranean dietary pattern in Italy.

Summary: Diagnosing chronic myeloid leukaemia (CML) during pregnancy is rare. Tyrosine kinase inhibitors (TKIs) have traditionally been contraindicated owing to their teratogenicity. Management decisions should consider the risks to mother and foetus of uncontrolled disease and teratogenic medications. Further cases are required to build upon the paucity of current literature. We report 22 cases of CML diagnosed during pregnancy from 2002 to date. Twenty‐one pregnancies resulted in healthy babies and one patient miscarried. Some patients remained untreated throughout pregnancy but the majority received one or both of interferon‐α and leucapheresis. One patient was started on imatinib at Week 26, and one on hydroxycarbamide in the third trimester. We report haematological parameters during pregnancy to provide clinicians with realistic expectations of management. There were no fetal abnormalities related to treatment during pregnancy. Seventeen patients achieved at least major molecular response on first‐line TKI. A diagnosis of CML during pregnancy can be managed without significant consequences for mother or child. Leucapheresis and interferon‐α are generally safe throughout pregnancy. Despite having been avoided previously, there is growing evidence that certain TKIs may be used in particular circumstances during the later stages of pregnancy. Future work should aim to further elucidate this safety profile. [ABSTRACT FROM AUTHOR]

Objectives The present work aims to present the results of the ‘PRESTOinsieme’ (which is ‘we will be together soon’ in English). The web-based survey (www.prestoinsieme.com) describes changes in lifestyle habits and symptoms of psychological discomfort in the Italian population during the COVID-19 lockdown.Design Cross-sectional online survey disseminated by messaging apps (ie, WhatsApp and Telegram) and social networks (ie, Instagram, Facebook and LinkedIn).Setting Italy.Participants Italian population older than 16 years of age.Exposure COVID-19 lockdown.Main outcomes and measures Survey respondents filled out a set of validated questionnaires aimed at assessing lifestyle habits and psychological health, that is, the General Health Questionnaire (GHQ-12) to screen for psychological distress, the Impact of Event Scale-Revised (IES-R) to screen for post-traumatic stress and the Center for Epidemiologic Studies Depression Scale (CES-D).Results Survey respondents totalled 5008. Moderate or severe psychological distress was reported in 25.5% and 22% of survey respondents, respectively. Lower age, female gender, being unemployed (OR 1.57, 95% CI 1.22 to 2.02) or being a student (OR 1.73, 95% CI 1.31 to 2.28) were predictors of more severe depressive symptoms.Conclusions The present study is one of the largest population-based surveys conducted in Italy during the first COVID-19 lockdown, providing valuable data about the Italian population’s psychological health. Further studies should be conducted to understand whether psychological distress persists after the end of the lockdown.

The High Agri Valley is a tectonically active area in southern Italy characterized by high seismic hazard related to fault systems capable of generating up to M=7 earthquakes (i.e. the 1857 Mw=7 Basilicata earthquake). In addition to the natural seismicity, two different clusters of induced microseismicity were recognized to be caused by industrial operations carried out in the area: (1) the water loading and unloading operations in the Pertusillo artificial reservoir and (2) the wastewater disposal at the Costa Molina 2 injection well. The twofold nature of the recorded seismicity in the High Agri Valley makes it an ideal study area to deepen the understanding of driving processes of both natural and anthropogenic earthquakes and to improve the current methodologies for the discrimination between natural and induced seismic events by collecting high-quality seismic data. Here we present the dataset gathered by the INSIEME seismic network that was installed in the High Agri Valley within the SIR-MIUR research project INSIEME (INduced Seismicity in Italy: Estimation, Monitoring, and sEismic risk mitigation). The seismic network was planned with the aim to study the two induced seismicity clusters and to collect a full range of open-access data to be shared with the whole scientific community. The seismic network is composed of eight stations deployed in an area of 17 km×11 km around the two clusters of induced microearthquakes, and it is equipped with triaxial weak-motion broadband sensors placed at different depths down to 50 m. It allows us to detect induced microearthquakes, local and regional earthquakes, and teleseismic events from continuous data streams transmitted in real time to the CNR-IMAA Data Centre. The network has been registered at the International Federation of Digital Seismograph Networks (FDSN) with code 3F. Data collected until the end of the INSIEME project (23 March 2019) are already released with open-access policy through the FDSN web services and are available from IRIS DMC (https://doi.org/10.7914/SN/3F_2016; Stabile and INSIEME Team, 2016). Data collected after the project will be available with the permanent network code VD (https://doi.org/10.7914/SN/VD, CNR IMAA Consiglio Nazionale delle Ricerche, 2019) as part of the High Agri Valley geophysical Observatory (HAVO), a multi-parametric network managed by the CNR-IMAA research institute.

Based on the RILEM Technical Committee 274-TCE work, this paper is a discussion of the remaining engineering challenges faced by earthen architecture. The assessment of earth material performances requires the development of appropriate procedures and standards. This is discussed in particular for the characterisation, hygrothermal behaviour, mechanical behaviour, and durability of earth materials. One other important challenge, since one of the main advantages classically put forward, is its ecological performance, is a proper assessment of life cycle assessment of earth materials, elements and buildings. Moreover, the paper develops why the approach to earthen construction must be different compared to the dominant construction materials, to preserve its ability to contribute to the ecological transition in the construction sector. In particular, the needs of using local soils, with an architectural approach coping with the limits of the materials, and developing an architectural optimisation to preserve the earthen materials multifunctionality rather than selecting a sole property to be maximised. Lastly, the findings of the paper can be used to develop a holistic approach to earthen construction to foster the development of new earthen architecture projects.

The growing pressures of climate change, increased usage and unprecedented geo-hazards impose a modification in the way civil engineering structures are designed and constructed. This isparticularly true for geotechnical works, which are very sensitive to changes of environmental conditions. For instance, the response of a pile under lateral loading is strongly influenced by the stiffness and strength of the first few metres of soil below the surface, which are often partly saturated. To consider this effect, the present paper describes an analytical method, which extends the well-known Broms approach to predict thelateral capacity of piles in unsaturated soils. More specifically, the proposed method considers the combined effects of the position of the ground water table and the extra strength of the partially saturated soil above it. Compared to Broms approach, the solution introduces four additional non-dimensional parameters that relate the soil-water retention behaviour to the geometry of the pile. The method provides a direct evaluation of the lateral pile capacity in partly saturated soils, which can be used as a basis for more accurate design.

This paper extends the modified Cam-Clay model to describe the behaviour of unsaturated soils by replacing the effective stress with the scaled stress. The scaled stress accounts for the mechanical effect of capillarity by factoring Bishop’s stress with a power function of degree of saturation. The extendedmodified Cam-Clay model postulates the existence of a yield curve in the mean scaled stress 𝑝̅– deviatoric scaled stress 𝑞̅ plane. Coherently with the modified Cam-Clay model, the stress-strain behaviour is predicted by means of an elastic law inside the yield curve. As the scaled stress state evolves onto the yield curve, the behaviour becomes elasto-plastic and this is modelled by a plastic flow rule combined with a volumetric hardening law. The extended modified Cam-Clay model is then validated against experimental data published in the literature. Results show that the proposed approach is capable of well predicting the mechanical behaviour of unsaturated soils during triaxial loading. Future work will be directed at further validating the present formulation along different stress paths as well as accounting for the combined effect of partial saturation and cementation within a critical state framework based on bounding surface plasticity.

Raw earth is emerging as a viable building material with lower carbon emissions than conventional concrete and fired bricks. Raw earth is as an excellent passive hygro-thermal regulator, which improves occupants’ comfort while reducing the need for active heating/cooling installations. The coupled hygro-thermal response of earth materials is investigated by exploiting the principles of the thermodynamics of porous media and unsaturated soil mechanics. The degree of coupling between temperature and relative humidity (or water content) depends on the adopted simplifying assumptions. Some of these assumptions are valid for traditional building materials but may not be applicable to raw earth characterised by relatively high levels of liquid/gas permeability. The validity of current approaches is here assessed with reference to earth building via a simple one-dimensional transfer model, which simulates the behaviour of an unbounded earth wall subjected to time-dependent boundary conditions on the two faces. For typical values of water and vapour permeability, the complexity of the governing equations can be greatly reduced by neglecting variations of vapour mass and the dependency of suction on temperature without significantly reducing accuracy. Results are also strongly influenced by both initial state and water retention properties of the earth material.

High capacity tensiometers (HCT) allow the direct measurement of soil matric suction, and their major limitation is the occurrence of cavitation. In this paper HCT designs using different ceramic filters with varied air entry values (AEV), varied reservoir sizes, and different pressure transducers are assessed as to determine the impact that each component may have in the HCT performance. Moreover, the effectiveness of first saturation and resaturation processes is discussed in relation to the time required to prepare/recover HCTs. The results obtained with the different designs show that the measuring range is directly linked to the AEV of the ceramic filter and that the choice of materials used for the various components may affect the reliability of measurements in field installations if the thermal performance is not accounted for in the calibration procedure. The use of a 1hr high vacuum pre-stage followed by overnight water pressurisation at pressures equal or above the AEV of the ceramic filter was found to be the quickest process to fully saturate an HCT for the first time. While resaturation time for an HCT can be reduced to as little as a few minutes if the HCT is resaturated immediately after cavitation has occurred.

Pseudomonas syringae pv. actinidiae is an important pathogen of kiwifruit (Actinidia deliciosa), and bacterial canker of this host is managed by monitoring and chemical control strategies. The efficacy of the bio-pesticides Amylo-X® (based on Bacillus amyloliquefaciens subsp. plantarum strain D747) and Serenade Max® (strain QST713 of B. subtilis) was evaluated by in vitro and in vivo experiments. Both antagonists inhibited different biovars of the pathogen in in vitro assays; QST713 was more efficient than D747. The two Bacillus strains also colonized A. deliciosa flowers (c. 105-7 cfu per flower) up to 96 h after inoculation. D747 persisted on leaves (c. 104-6 cfu cm-2) up to 4 weeks after inoculation, during 2 years in Emilia Romagna and Latium regions of Italy. On flowers, the antagonists reduced pathogen populations, compared to untreated (control) flowers. On A. deliciosa and A. chinensis plants under controlled conditions, Amylo-X® reduced severity of bacterial canker, providing ca. 50% relative protection on A. deliciosa and 70% on A. chinensis. Serenade Max® was less effective, giving 0% relative protection on A. deliciosa and 40% on A. chinensis. In a field trial, on A. deliciosa plants, Amylo-X® reduced the severity of bacterial canker on leaves, providing ca. 40% relative protection. The sensitivity of both antagonistic strains to streptomycin sulphate was confirmed by testing the most used concentration where antibiotics are approved for management of bacterial pathogens.

A geophysical approach, based on the integration of satellite differential interferometric SAR technique and in situ geoelectrical and seismic methods, was applied with the aim to characterize a portion of urban area of Avigliano (PZ) town in Basilicata Region (southern Italy) affected by ground instability phenomena. Satellite analysis helped to discriminate areas of the town affected by superficial deformations and to monitor the dynamic behaviour of the structures located in these areas. Results from geoelectrical and seismic (active and passive) methods were compared with direct data (stratigraphic) and were interpreted with the aim to reconstruct the geometry of the subsoil. The joint application of both in situ techniques allowed the overcoming of the specific limits of each method and to improve the poor quality of the data due to the noise conditions typical of measurements carried out in urban areas. A preliminary geophysical model of the subsoil was obtained. The geophysical contrasts highlighted the presence of lithological discontinuities due to the superficial deformation processes that are affecting the portion of the investigated urban area. All the information has been transferred to the public administration technicians involved in the mitigation of hydrogeological risk in Basilicata Region.

Despite significant recent advances in our understanding of the biology and genetics of acute myeloid leukemia (AML), current AML therapies are mostly based on a backbone of standard chemotherapy which has remained mostly unchanged for over 20 years. Several novel therapies, mostly targeting neomorphic/activating recurrent mutations found in AML patients, have only recently been approved following encouraging results, thus providing the first evidence of a more precise and personalized approach to AML therapy. Rewired metabolism has been described as a hallmark of cancer and substantial evidence of its role in AML establishment and maintenance has been recently accrued in preclinical models. Interestingly, unique metabolic changes are generated by specific AML recurrent mutations or in response to diverse AML therapies, thus creating actionable metabolic vulnerabilities in specific patient groups. In this review we will discuss the current evidence supporting a role for rewired metabolism in AML pathogenesis and how these metabolic changes can be leveraged to develop novel personalized therapies.

La categoría de copia en el ámbito artístico ha estado sujeta a una extensa y compleja multiplicidad de definiciones. El objetivo de este artículo es analizar una serie de premisas relativas a la construcción de la copia, su relación con los calcos escultóricos y su aplicabilidad a ellos. Se toma como caso de estudio una variedad de calcos escultóricos del David de Miguel Ángel en función de explorar sus particularidades objetuales y materiales y de examinar qué categoría de copia es pertinente emplear. En este sentido, se coteja el concepto de copia, réplica y falso

SRPK1, a kinase involved in splicing regulation, is a potential therapeutic target for AML patients. Here, the authors show that SRPK1 inhibition changes isoform levels of key epigenetic regulators, including BRD4, and it has anti-tumor effects specifically against MLL-rearranged AML cells.

Monitoring seismic structural response is an essential issue in earthquake risk assessments and mitigation studies for monumental buildings in order to undertake earthquake disaster management. This study aims at identifying the resonant frequency of soil and modern and historical buildings in three major municipalities of Crete (Heraklion, Chania, and Rethymno) using ambient noise recordings (microtremors) considering the importance of soil–structure interaction to seismic structural response, particularly for historical buildings and monumental structures. In this study, ambient noise recordings have been processed through Horizontal to Vertical Spectral Ratios (H/V) to preliminarily examine the main frequencies and to examine whether the building has its main frequency close to that of the soil in order to identify potential resonance phenomena. Numerous ambient noise recordings were recorded on the soil, in the basement, and at each n-floor of the buildings. The incorporation of local site conditions and soil-building resonance phenomena into the urban planning development of Crete regarding earthquake risk assessments is necessary. In this direction, microtremors can be used as an effective tool to support civil protection preparation and operational decision-making in terms of earthquake disaster, specifically in the area of Crete, which is characterized by high seismic activity and a high cultural monuments capacity.