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Nachhaltige Entwicklung erfordert die Auseinandersetzung mit Wechselwirkungen zwischen unterschiedlichen Ressourcen und – angesichts der Komplexität dieser Zusammenhänge – die Bereitschaft, auch ins Ungewisse hinein zu entscheiden und zu handeln. Diese Entscheidungen und Handlungen müssen kontinuierlich reflektiert und im Hinblick auf ihre Effekte bewertet werden – auch in Lern- oder Bildungsprozessen. Solche Entwicklungsprozesse sind im Beitrag theoretisch als Neu-Konstellationen von Ressourcen-, Merkmals- oder Verhaltenszusammenhängen (Konstellationen) gefasst, wobei sich Neu-Konstellation aus Probehandeln im Sinn von handelnder (performativer) Reflexion ergibt. Vor diesem Hintergrund nimmt der vorliegende Beitrag das Erasmus+ Projekt „Bridging Barriers“ zum Anlass, um das spezifische Potenzial partizipativer Settings in der Erwachsenenbildung für die Auseinandersetzung mit nachhaltigen Entwicklungsprozessen aufzuzeigen. In diesem Projekt hat die Autorin eine Weiterbildung für erfahrene Basisbildner*innen konzipiert, in der die Teilnehmer*innen durch verschiedene Formen von kollaborativer Aneignung von theoretischen Konzepten und Fallarbeit ihre impliziten Kompetenzen reflektierten und dabei auch weiterentwickelten. Die Teilnehmer*innen konnten das gezielt offen angelegte Setting mitgestalten, was Verständigungs- und Aushandlungsprozesse erforderte und so einen partizipativen Bildungsprozess ermöglichte. Genau solche kollaborativen und partizipativen Reflexions- und Lernprozesse sind nach Ansicht der Autorin auch für eine nachhaltige Entwicklung notwendig. (Red.)

Abstract Objective To describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation. Design Systematic review with an individual data meta-analysis. Setting Observational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes. Population Patients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h. Main outcome measures The primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio. Results The meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I 2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I 2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I 2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I 2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I 2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I 2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Thus, six FDA-approved commercial CAR-T cell products that target antigens preferentially expressed on malignant B-cells or plasma cells have been introduced in the therapy of B-cell lymphomas, B-ALLs and multiple myeloma. These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies. However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited to the existence of some limiting factors, such as the sharing of mutual antigens between normal T-cells and CAR-T cells, and malignant cells, determining fratricide events and severe T-cell aplasia; contamination of CAR-T cells used for CAR transduction with contaminating malignant T-cells. Allogeneic CAR-T products can avoid tumor contamination but raise other problems related to immunological incompatibility. In spite of these limitations, there has been significant progress in CD7- and CD5-targeted CAR-T cell therapy of T-cell malignancies in the last few years.

Penetrating trauma is usually divided into stab and gunshot wounds (GSW). When considering GSW, the initial assessment involves the identification of all the wounds, to understand the projectile's trajectory as well as to determine which anatomic structures might have been damaged [1]. Rarely, the projectile might not leave the victim's body and embolize to a different region through large blood vessels. Known as Missile Embolism (ME), this uncommon complication can compromise multiple body segments, resulting in severe injuries, whether it occurs through an artery or a vein, such as pulmonary embolism, cardiac-valve incompetence, limb-threatening ischemia, coronary infarct, and stroke [2,3]. This is a case report of an 18-year-old male patient who suffered a gunshot wound and was submitted to an exploratory laparotomy which identified a laceration of the inferior vena cava. Further exams concluded that the bullet was embolized to the right hepatic vein. ME treatment will depend mostly on the bullet's placement; if located in the left circulation or arterial vessels, retrieval is the preferred treatment. It can be executed through surgical exploration or endovascular procedure [3,4,8] Venous ME has several treatment options, including conservative management if the patient remains asymptomatic [3–7]. Cases of paradoxical embolization might be managed as arterial ME [3,4].

The use of two nozzle diameters (6 and 8 mm) in a cold (50°C) hemp seed oil extraction process was evaluated in terms of extraction efficiency, and chemical composition and in vitro fermentation characteristics of the residual cake. Seeds of the varieties Futura 75 and Uso 31 were pressed using a mechanical press with a cooling device. Five pressings were carried out for each variety and nozzle size, the functional parameters of the extraction processes were recorded, and sample of the residual cakes (n = 20) were analyzed. The 6 mm nozzle determined a higher oil yield (+4%) with a limited increase in temperature in the pressing chamber and in the oil (on average + 3°C compared to the 8 mm nozzle). A lower oil yield and consequently a higher fat content in the corresponding cake was observed when using the 8 mm nozzle. Despite the similar fat content, the two varieties had different oil yields and different residual cake compositions. The gas production kinetic of cakes was influenced by variety but little by nozzle size. Overall, the use of a smaller nozzle in a temperature-controlled extraction process can be a useful option to increase hemp oil yield while maintaining good fermentation characteristics of the residual cakes as ruminant feed.

Treatment of refractory and relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) is an unmet medical need in both children and adults. Studies carried out in the last two decades have shown that autologous T cells engineered to express a chimeric antigen receptor (CAR-T) represent an effective technique for treating these patients. Antigens expressed on B-cells, such as CD19, CD20, and CD22, represent targets suitable for treating patients with R/R B-ALL. CD19 CAR-T cells induce a high rate (80-90%) of complete remissions in both pediatric and adult R/R B-ALL patients. However, despite this impressive rate of responses, about half of responding patients relapse within 1-2 years after CAR-T cell therapy. Allo-HSCT after CAR-T cell therapy might consolidate the therapeutic efficacy of CAR-T and increase long-term outcomes; however, not all the studies that have adopted allo-HSCT as a consolidative treatment strategy have shown a benefit deriving from transplantation. For B-ALL patients who relapse early after allo-HSCT or those with insufficient T-cell numbers for an autologous approach, using T cells from the original stem cell donor offers the opportunity for the successful generation of CAR-T cells and for an effective therapeutic approach. Finally, recent studies have introduced allogeneic CAR-T cells generated from healthy donors or unmatched, which are opportunely manipulated with gene editing to reduce the risk of immunological incompatibility, with promising therapeutic effects. Keywords: CAR T; Acute Lymphoid Leukemia; Allogeneic CAR-T; Autologous CAR-T.

Follicular lymphoma is the second most diagnosed lymphoma in Western Europe. Significant advancements have considerably improved the survival of FL patients. However, 10-20% of these patients are refractory to standard treatments, and most of them will relapse. The treatment of follicular lymphoma patients with multiply relapsed or refractory disease represents an area of high-unmet needing new treatments with stronger efficacy. Chimeric antigen receptor (CAR)-T cell therapy targeting B-cell antigens, such as CD19 or CD20, is emerging as an efficacious treatment for R/R follicular lymphoma patients, particularly for those with early relapse and refractory to alkylating agents and to anti-CD20 monoclonal antibodies, resulting in a high rate of durable responses in a high proportion of patients.

ABSTRACTNatural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells. However, the involvement of exosomal miRNAs in the function of NK exosomes is poorly understood. In this study, we explored the miRNA content of NK exosomes by microarray as compared to their cellular counterparts. The expression of selected miRNAs and lytic potential of NK exosomes against childhood B acute lymphoblastic leukemia cells after co-cultures with pancreatic cancer cells were also evaluated. We identified a small subset of miRNAs, including miR-16-5p, miR-342-3p, miR-24-3p, miR-92a-3p and let-7b-5p that is highly expressed in NK exosomes. Moreover, we provide evidence that NK exosomes efficiently increase let-7b-5p expression in pancreatic cancer cells and induce inhibition of cell proliferation by targeting the cell cycle regulator CDK6. Let-7b-5p transfer by NK exosomes could represent a novel mechanism by which NK cells counteract tumor growth. However, both cytolytic activity and miRNA content of NK exosomes were reduced upon co-culture with pancreatic cancer cells. Alteration in the miRNA cargo of NK exosomes, together with their reduced cytotoxic activity, could represent another strategy exerted by cancer to evade the immune response. Our study provides new information on the molecular mechanisms used by NK exosomes to exert anti-tumor-activity and offers new clues to integrate cancer treatments with NK exosomes.

AbstractBackground Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis.Methods Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method.Results Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81–5.30, p

Abstract Background Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality. Methods Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included. Results Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p

Abstract Background There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2–15.1], 13 J/min [IQR 10–17], and 14 J/min [IQR 11–20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14–1.30) and HD3 (1.38, 95% CI 1.23–1.53), reintubation on HD1 (1.64; 95% CI 1.57–1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18–1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56–2.78) and HD3 (1.76; 95% CI 1.41–2.22). Conclusions Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.

Abstract Background There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. Methods We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P 0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P 0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). Results Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P 0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047–1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997–0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267–1.867, p

Abstract Background Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. Methods We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early ( 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. Results Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0–3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = − 0.3, 95% CI = − 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). Conclusions In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. Trial registration: PROSPERO—CRD42022351732 registered on 17th of August 2022.

The disinfection of deteriogenic microorganisms and the removal of induced chromatic alterations in artworks are still open challenges in the field of conservation. For this purpose, a new alcoholic hydrogel was tested to remove an extensive fungal attack from a multimaterial collage by the artist Alessandro Kokocinski and to mitigate chromatic changes caused by the contamination of its poster paper and plywood support layers. A Gellan gum-based hydrogel was used, which was modified by adding a high concentration of alcohol (66.7% ethanol), to give the system an effective disinfecting agent in addition to the detergent capacity of the gel for water-sensitive works of art. It was successfully tested on samples mimicking the complex stratigraphy of the artwork under study. To create replica mock-ups, the artwork materials and stratigraphy were investigated through diagnostic and laboratory techniques such as multispectral imaging, X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis coupled with gas-chromatography-mass spectrometry. The treatment was shown to have a disinfecting effect on the test samples and did not alter their structure, allowing us to apply the method to the artwork. Here, the hydrogel successfully removed and inhibited fungal proliferation in addition to mitigating the color changes caused by fungi.

This work was carried out for a master’s degree thesis concerning the conservation of a contemporary artwork made by the surrealist artist Roberto Sebastian Matta. The artwork is a large (one central panel 180.3 × 405.1 cm; two side panels 179.1 × 150.6 cm) triptych created in 1974 with pastels on tracing paper adhered onto canvas as a secondary support. After thoroughly studying the execution technique and conservation status of the artwork, several issues arose, including a strong acid hydrolysis of both the paper and canvas supports. We focused our intervention on deacidification treatments by comparing either traditional substances, such as calcium propionate in an alcoholic solution, or more innovative methods, such as a nanostructured calcium hydroxide in isopropyl alcoholic solution. Acid hydrolysis degradation was the most difficult issue to address because of the size of the artwork and for the different sensitivities to aqueous methods of the materials used to make the artwork. For the first time to our knowledge, we used an innovative deacidification method consisting of nanostructured calcium hydroxide particles. This intervention would allow the homogeneous atomization of the deacidifying agent in alcoholic solvents to be safe and effective for the work as a whole.

The clothoid is a planar curve with the intuitive geometrical property of a linear variation of the curvature with arc length, a feature that is important in many geometric design applications. However, the exact parameterization of the clothoid is defined in terms of the irreducible Fresnel integrals, which are computationally expensive to evaluate and incompatible with the polynomial/rational representations employed in computer aided geometric design. Consequently, applications that seek to exploit the simple curvature variation of the clothoid must rely on approximations that satisfy a prescribed tolerance. In the present study, we investigate the use of planar Pythagorean-hodograph (PH) curves as polynomial approximants to monotone clothoid segments, based on geometric Hermite interpolation of end points, tangents, and curvatures, and precise matching of the clothoid segment arc length. The construction, employing PH curves of degree 7, involves iterative solution of a system of five algebraic equations in five real unknowns. This is achieved by exploiting a closed-form solution to the problem of interpolating the specified data (except the curvatures) using quintic PH curves, to determine starting values that ensure rapid and accurate convergence to the desired solution.

The clothoid is a planar curve with the intuitive geometrical property of a linear variation of the curvature with arc length, a feature that is important in many geometric design applications. However, the exact parameterization of the clothoid is defined in terms of the irreducible Fresnel integrals, which are computationally expensive to evaluate and incompatible with the polynomial/rational representations employed in computer aided geometric design. Consequently, applications that seek to exploit the simple curvature variation of the clothoid must rely on approximations that satisfy a prescribed tolerance. In the present study, we investigate the use of planar Pythagorean-hodograph (PH) curves as polynomial approximants to monotone clothoid segments, based on geometric Hermite interpolation of end points, tangents, and curvatures, and precise matching of the clothoid segment arc length. The construction, employing PH curves of degree 7, involves iterative solution of a system of five algebraic equations in five real unknowns. This is achieved by exploiting a closed-form solution to the problem of interpolating the specified data (except the curvatures) using quintic PH curves, to determine starting values that ensure rapid and accurate convergence to the desired solution.

BackgroundIt is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28).MethodsThis is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma.ResultsA total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures

Wooden Cultural Heritage (WCH) represents a significant portion of the world’s historical and artistic heritage, consisting of immovable and movable artefacts. Despite the expertise developed since ancient times to enhance its durability, wooden artefacts are inevitably prone to degradation. Fungi play a pivotal role in the deterioration of WCH in terrestrial ecosystems, accelerating its decay and leading to alterations in color and strength. Reviewing the literature of the last 25 years, we aimed to provide a comprehensive overview of fungal diversity affecting WCH, the biochemical processes involved in wood decay, and the diagnostic tools available for fungal identification and damage evaluation. Climatic conditions influence the occurrence of fungal species in threatened WCH, characterized by a prevalence of wood-rot fungi (e.g., Serpula lacrymans, Coniophora puteana) in architectural heritage in temperate and continental climates and Ascomycota in indoor and harsh environments. More efforts are needed to address the knowledge fragmentation concerning biodiversity, the biology of the fungi involved, and succession in the degradative process, which is frequently centered solely on the main actors. Multidisciplinary collaboration among engineers, restorers, and life sciences scientists is vital for tackling the challenges posed by climate change with increased awareness. Traditional microbiology and culture collections are fundamental in laying solid foundations for a more comprehensive interpretation of big data.

Beyond solar and wind energy, wave energy is gaining great interest due to its very high theoretical potential, although its stochastic nature causes intermittent and fluctuating power production. Energy storage system (ESS) integration to wave energy converter (WEC) plants represents a promising solution to mitigate this issue. To overcome the technological limits of the single storage devices, the hybridization of complementary ESSs represents an effective solution, extending the operating range over different timeframes. This paper analyzes the benefits of Li-ion battery–supercapacitor hybrid ESS integration into a grid-connected WEC, aiming at smoothing the produced power oscillations. The hybridization concept involves coupling a power-intensive technology, such as a supercapacitor devoted to managing fluctuations at higher frequency, with a battery technology exploited to manage power variations over longer timeframes to mitigate degradation issues. In this study, a multi-objective data-driven power management strategy, based on the simultaneous perturbation stochastic approximation (SPSA) algorithm, is implemented to minimize power fluctuations in terms of power ramp (representing the power variation between two consecutive values with a 1 s time step), both at the Point of Common Coupling (PCC) and the Li-ion battery terminals, thanks to the supercapacitor peak-shaving function. The SPSA management strategy, together with a suitable sizing procedure, allows a reduction of more than 70% in the power oscillations at the PCC with respect to those at the WEC terminals, while decreasing battery stress by more than 25% if compared to a non-hybrid ESS consisting of a Li-ion battery. This shows how supercapacitor features can extend battery lifespan when integrated in a hybrid ESS.

The continuous advances in numerical modeling of the atmosphere, computing power and data assimilation techniques entail frequent updates of numerical weather prediction (NWP) models that show improved forecast skill. This circumstance leads to the recurrent delivery of revised reanalysis databases that provide weather estimates for several decades back in time by combining the latest NWP models with observations. Since climate studies and agriculture water management applications require the availability of accurate and reliable weather data, assessing the performance of reanalysis products contributes to informed choices of potential weather proxy of ground-based agrometeorological data. CERRA (Copernicus European Regional ReAnalysis) dataset is the latest regional reanalysis product released by the European Centre for Medium-Range Weather Forecasts (ECMWF), in August 2022. CERRA is forced by the global ERA5 reanalysis, and it provides weather data with resolution of 5.5 km for the pan-European territory from 1984. For the first time in literature, this study explores the performance of CERRA data at 38 ground-based weather stations located in Sicily, an Italian region with Mediterranean climate, during the irrigation seasons 2003–2022. The objective of the study lies in evaluating CERRA performance with respect to air temperature, actual vapor pressure, wind speed and solar radiation that are input variables for assessing reference evapotranspiration, ETO, which is a key variable for quantifying irrigation volumes needed for water resources studies. The accuracy of ETO estimates depends on those input variables through the equation provided by the Food and Agriculture Organization of the United Nations (FAO), i.e., the FAO Penman-Monteith equation. Here, it is also evaluated the performance of ETO estimates by using CERRA weather inputs in the FAO Penman-Monteith equation. The results show that the performances of CERRA weather data are excellent, especially for air temperature, and this determines that CERRA ETO estimates present high accuracy and reliability with a mean PBIAS and NRMSE equal to 5.6% and 13%, respectively, over the region. Those outcomes lead to the conclusion that CERRA dataset represents a valid alternative to ground-based agrometeorological measurements and their spatial interpolation for water resource regional studies.

Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin’s lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies. CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. The use of CAR-T cell therapy has also been explored for the treatment of high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement. Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T: therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials are evaluating bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and to reduce the number of refractory/relapsing patients.

Background: Wave energy represents one of the most promising renewable energies due to its great theoretical potential. Nevertheless, the electrical compliance of grid-connected systems is a great issue nowadays, due to the highly stochastic nature of wave energy. Methods: In this paper, a Hybrid Energy Storage System (HESS) consisting of a Li-ion battery and a flywheel is coupled to a Wave Energy Converter (WEC) that operates in grid connected mode. The study is performed using real yearly wave power profiles relating to three different sites located along the European coasts. The Simultaneous Perturbation Stochastic Approximation (SPSA) principle is implemented as real-time power management strategy for HESS in wave energy conversion systems. Results: Obtained results demonstrate how the proposed HESS and the implementation of the SPSA power management coupled to a WEC allow a reduction of more than 80% of power oscillations at the Point of Common Coupling (PCC), while proving the robustness of the developed management strategy over the investigated sites. Moreover, the average energy penalty due to the HESS integration results slightly higher than 5% and battery solicitation is reduced by more than 64% with respect to the flywheel solicitation, contributing to extend its lifetime. Conclusions: HESS integration in renewable generation systems maximizes the WEC production while smoothing the power at the PCC. Specifically, flywheel-battery HESS together with the implemented power management strategy could provide a great flexibility in the view of increasing power production from waves, strongly mitigating the variability of this source while enhancing grid safety and stability.

L-DOPA-induced dyskinesia (LID) is a frequent adverse side effect of L-DOPA treatment in Parkinson's disease (PD). Understanding the mechanisms underlying the development of these motor disorders is needed to reduce or prevent them. We investigated the role of TrkB receptor in LID, in hemiparkinsonian mice treated by chronic L-DOPA administration. Repeated L-DOPA treatment for 10 days specifically increased full-length TrkB receptor mRNA and protein levels in the dopamine-depleted dorsal striatum (DS) compared to the contralateral non-lesioned DS or to the DS of sham-operated animals. Dopamine depletion alone or acute L-DOPA treatment did not significantly increase TrkB protein levels. In addition to increasing TrkB protein levels, chronic L-DOPA treatment activated the TrkB receptor as evidenced by its increased tyrosine phosphorylation. Using specific agonists for the D1 or D2 receptors, we found that TrkB increase is D1 receptor-dependent. To determine the consequences of these effects, the TrkB gene was selectively deleted in striatal neurons expressing the D1 receptor. Mice with TrkB floxed gene were injected with Cre-expressing adeno-associated viruses or crossed with Drd1-Cre transgenic mice. After unilateral lesion of dopamine neurons in these mice, we found an aggravation of axial LID compared to the control groups. In contrast, no change was found when TrkB deletion was induced in the indirect pathway D2 receptor-expressing neurons. Our study suggests that BDNF/TrkB signaling plays a protective role against the development of LID and that agonists specifically activating TrkB could reduce the severity of LID.