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Hydrophobic non-ionic (type V) deep eutectic solvents (DESs) have recently emerged as a new class of sustainable materials that have shown unique properties in several applications. In this study, type V DESs thymol : camphor, menthol : thymol and eutectic mixtures (EMs) based on menthol : carboxylic acids with variable chain length, are experimentally investigated using xenon NMR spectroscopy, with the aim to clarify the peculiar nanostructure of these materials. The results, obtained from the analysis of the 129Xe chemical shifts and of the longitudinal relaxation times, reveal a correlation between the deviation from ideality of the DESs and their structure free volume. Furthermore, the effect of varying the composition of DESs and EMs on the liquid structure is also studied.

Composite polymer electrolytes are systems of choice for future solid-state lithium metal batteries (LMBs). Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) is among the most interesting matrices to develop new generation quasi-solid electrolytes (QSEs). Here it is reported on nanocomposites made of PVDF-HFP and pegylated SiO2 nanoparticles. Silica-based hybrid nanofillers are obtained by grafting chains of poly(ethylene glycol) methyl ether (PEG) with different molecular weight on the surface of silica nanoparticles. The functionalized nanofiller improves the mechanical, transport and electrochemical properties of the QSEs, which show good ionic conductivity values and high resistance against dendrite penetration, ensuring boosted long and safe device operation. The most promising result is obtained by dispersing 5 wt% of SiO2 functionalized with short PEG chains (PEG750, Mw = 750 g mol−1) in the PVDF-HFP matrix with an ease solvent-casting procedure. It shows ionic conductivity of 0.1 mS cm−1 at 25 °C, more than 250 h resistance to stripping/plating, and impressive results during cycling tests in LMB with LiFePO4 cathode.

SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because SETBP1 mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed a myeloid neoplasm with megakaryocytic dysplasia, splenomegaly, and bone marrow fibrosis, prompting us to investigate SETBP1 mutations in a cohort of 36 triple-negative primary myelofibrosis (TN-PMF) cases. We identified 2 distinct subgroups, one carrying SETBP1 mutations and the other completely devoid of somatic variants. Clinically, a striking difference in disease aggressiveness was noted, with patients with SETBP1 mutation showing a much worse clinical course. In contrast to myelodysplastic/myeloproliferative neoplasms, in which SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in 3 patients with TN-PMF from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Recently, there has been an increase in telemedicine applied to child neuropsychiatry, such as the use of online platforms to collect remotely case histories and demographic and behavioral information. In the present proof-of-concept study, we aimed to understand to what extent information parents and teachers provide through online questionnaires overlaps with clinicians’ diagnostic conclusions on attention-deficit/hyperactivity disorder (ADHD). Moreover, we intended to explore a possible role that autism spectrum disorders (ASD) symptoms played in this process. We examined parent- and teacher-rated questionnaires collected remotely and an on-site evaluation of intelligence quotients from 342 subjects (18% females), aged 3–16 years, and referred for suspected ADHD. An easily interpretable machine learning model—decision tree (DT)—was built to simulate the clinical process of classifying ADHD/non-ADHD based on collected data. Then, we tested the DT model’s predictive accuracy through a cross-validation approach. The DT classifier’s performance was compared with those that other machine learning models achieved, such as random forest and support vector machines. Differences in ASD symptoms in the DT-identified classes were tested to address their role in performing a diagnostic error using the DT model. The DT identified the decision rules clinicians adopt to classify an ADHD diagnosis with an 82% accuracy rate. Regarding the cross-validation experiment, our DT model reached a predictive accuracy of 74% that was similar to those of other classification algorithms. The caregiver-reported ADHD core symptom severity proved the most discriminative information for clinicians during the diagnostic decision process. However, ASD symptoms were a confounding factor when ADHD severity had to be established. Telehealth procedures proved effective in obtaining an automated output regarding a diagnostic risk, reducing the time delay between symptom detection and diagnosis. H

Transparent nanocomposite films made of surface-modified titanium dioxide nanoparticles and thermoplastic polyurethane are prepared via film casting approach showing enhanced refractive indexes and mechanical properties. Two different sets of composites were prepared up to 37.5 wt % of inorganic nanoparticles with a diameter <15 nm, one set using particles capped only with oleic acid and a second one with a bimodal system layer made of oleic acid and mPEO-5000 as coating agents. All of the composites show significantly enhanced refractive index and mechanical properties than the neat polymeric matrix. The transparency of nanocomposite films shows the excellent dispersion of the inorganic nanoparticles in the polymeric matrix avoiding aggregation and precipitation phenomena. Our study provides a facile and feasible route to produce transparent nanocomposite films with tunable mechanical properties and high refractive indices for various applications.

Scintillating materials can enable the discrimination of neutrons and charged particles from gamma rays by exploiting the pulse shape discrimination (PSD) technique. The ability to discriminate between high energy photons and ionizing particles is indeed useful in several fields, for example to estimate the power generated in nuclear reactors or to identify threat radioactive materials (Uranium-235 and Plutonium-230) from the reaction of other non-threat sources. PSD techniques involve a time-gated analysis of the transient voltage pulse generated in the photodetector of the scintillation counter. This analysis allows to distinguish between fast and slow components of the scintillation signal, i.e., prompt and delayed emission, whose relative intensity and lifetime depend on the type of the incident radiation . We demonstrated that sensitive and fast PSD detection can be achieved in nanostructured polymer scintillators. The material is made of a solid polymer matrix, which provides structural stability but is optically passive, liquid nanodomains containing an extremely high concentration of a triplet triplet-annihilation (TTA) dye and optionally a triplet sensitizer, so that the delayed fluorescence occurs even at ultra-low energy densities. In this work we investigated the PSD response of a series of nanostructured scintillators as a function of the composition, in order to point out the mechanism behind the sensitization of the delayed fluorescence intensity in the presence of a triplet sensitizer. The obtained results provide the guidelines for the design and fabrication of high performance nanostructured multiphase scintillators that can surpass the state-of the art, commercially available, PSD plastic scintillators.

Exosomes are promising therapeutics for tissue repair and regeneration to induce and guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes to control their biodistribution and targeting them in vivo to achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system for primed annexin A1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exomyo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from these ferromagnetic nanotubes in vivo to synergistically promote beneficial muscle responses in a murine animal model of Duchenne muscular dystrophy. Our findings provide insights into the development of exosome-based therapies for muscle diseases and, in general, highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution

The use of scintillators for the detection of ionizing radiation is a critical aspect in many fields, including medicine, nuclear monitoring, and homeland security. Recently, lead halide perovskite nanocrystals (LHP-NCs) have emerged as promising scintillator materials. However, the difficulty of affordably upscaling synthesis to the multigram level and embedding NCs in optical-grade nanocomposites without compromising their optical properties still limits their widespread use. In addition, fundamental aspects of the scintillation mechanisms are not fully understood, leaving the scientific community without suitable fabrication protocols and rational guidelines for the full exploitation of their potential. In this work, we realize large polyacrylate nanocomposite scintillators based on CsPbBr3 NCs, which are synthesized via a novel room temperature, low waste turbo-emulsification approach, followed by their in situ transformation during the mass polymerization process. The interaction between NCs and polymer chains strengthens the scintillator structure, homogenizes the particle size distribution and passivates NC defects, resulting in nanocomposite prototypes with luminescence efficiency >90%, exceptional radiation hardness, 4800 ph/MeV scintillation yield even at low NC loading, and ultrafast response time, with over 30% of scintillation occurring in the first 80 ps, promising for fast-time applications in precision medicine and high-energy physics. Ultrafast radioluminescence and optical spectroscopy experiments using pulsed synchrotron light further disambiguate the origin of the scintillation kinetics as the result of charged-exciton and multiexciton recombination formed under ionizing excitation. This highlights the role of nonradiative Auger decay, whose potential impact on fast timing applications we anticipate via a kinetic model.

Nowadays, the web presents real estate sites providing the possibility to use low-cost virtual reality (VR) solutions without sacrificing the high quality of graphic visualization of their contents to attract customers through enhanced digital experiences and increase the probability of selling their products. However, whether immersive VR technologies improve the chances of selling real estate is unclear. This study examines the effects induced by a real estate website that offers the opportunity to evaluate the potential purchase of a property in two ways: by viewing photos of the house (non-immersive conditions) and by taking a virtual tour of the same house using a VR head-mounted display (immersive conditions). Forty participants interested in evaluating the purchase of a new house, randomly assigned to one of the experimental conditions, participated in the experiment. During the real estate experience, electroencephalography (EEG) and skin conductance (SC) were recorded to collect biological data about the emotional effects raised by each condition. After the study, psychological self-reported questionnaires were collected measuring: emotions, presence, user experience (UX), and a three-item ad hoc scale exploring behavioral intentions (e.g., the perceived pleasantness of the house, the willingness to visit the house, and the purchase intention). Results show that immersive navigation is associated with more positive emotions (EEG), more intense physiological arousal (SC), higher scores on the presence questionnaire, and higher scores on the UX questionnaire compared to the non-immersive one. The psychological scales measuring emotions did not yield significant results. No significant difference in the three-item ad-hoc self-questionnaire was found, except for the item examining willingness to visit the real house building. Implications are also discussed.

The reversible gelation of aqueous methylcellulose (MC)solutionsat high temperature is followed stepwise with low-field time-domainnuclear magnetic resonance (LF-TD-NMR). The gel transition does notinfluence the self-diffusion coefficient of water but is associatedwith a decrease of proton transverse relaxation times H-1 T (2) by more than 60%. The effect ofmolecular weight and concentration of polysaccharide chains on transitiontemperature and gel strength is probed on several MCs with the samedegree of substitution. The measured trends connect the NMR relaxationwith macroscopic observables and agree with literature results frommore demanding techniques like small-angle X-ray and neutron scattering(SAXS and SANS). These findings support the idea of a network structureof disorderly arranged fibrils, with an inhomogeneous mesh size atleast on the order of tens of microns, which is in accord with theopaque appearance of these hydrogels. Magic sandwich echo (MSE) NMRmeasurements performed at 80 degrees C by substituting water with D2O also reveal the appearance with thermogelation of a rigidfraction involving about 25% of MC. This is consistent with the formationof fibrils mostly constituted by an amorphous matrix strongly permeatedby water and strengthened by well-dispersed MC crystallites.

Objective: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. Methods: Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.

Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed. Here, we describe one patient with severe developmental delay, sensoneurinal deafness, acute disseminated encephalomyelitis, hypogammaglobulinemia and recurrent infections. Pathogenic biallelic KARS1 variants (Phe291Val/ Pro499Leu) were associated with impaired B cell metabolism (decreased mitochondrial numbers and activity). All published cases of KARS-related diseases were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Seventeen patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported. Immunoglobulin replacement therapy was given in five patients. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment.

Background: Anemia (either pre-existing or hospital-acquired) is considered an independent predictor of mortality in acute coronary syndromes. However, it is still not clear whether anemia should be considered as a marker of worse health status or a therapeutic target. We sought to investigate the relationship between hospital-acquired anemia and clinical and laboratory findings and to assess the association with mortality and major cardiovascular events at long-term follow-up. Methods: Patients consecutively admitted at Niguarda Hospital between February 2014 and November 2020 for an acute coronary syndrome were included in this cohort analysis and classified as anemic at admission (group A), with normal hemoglobin at admission but developing anemia during hospitalization (hospital-acquired anemia) (group B); and with normal hemoglobin levels throughout admission (group C). Results: Among 1294 patients included, group A included 353 (27%) patients, group B 468 (36%), and group C 473 patients (37%). In terms of cardiovascular burden and incidence of death, major cardiovascular events and bleeding at 4.9-year median follow-up, group B had an intermediate risk profile as compared with A and C. Baseline anemia was an independent predictor of death (hazard ratio 1.51; 95% confidence interval, 1.02-2.25; P = .04) along with frailty, Charlson comorbidity Index, estimated glomerular filtration rate, previous myocardial infarction, and left ventricular ejection fraction. Conversely, hospital-acquired anemia was not associated with increased mortality (hazard ratio 1.18; 95% confidence interval, 0.8-1.75; P = .4). Conclusions: Hospital-acquired anemia affects one-third of patients hospitalized for acute coronary syndrome and is associated with age, frailty, and comorbidity burden, but was not found to be an independent predictor of long-term mortality.

During the submission of the accepted manuscript, first names and surnames had been inverted. The list of authors has been corrected above. The original version has been corrected.

The above article was published with error. The affiliation address of the authors Alberto Albanese and Tiziana De Santis has been modified to: “U.O. Neurologia, IRCCS Istituto Clinico Humanitas, Milan, Italy”.The Original article has been corrected.

Porous materials are ubiquitous systems with a large variety of applications from catalysis to polymer science, from soil to life science, from separation to building materials. Many relevant systems of biological or synthetic origin exhibit a hierarchy, defined as spatial organization over several length scales. Their characterization is often elusive, since many techniques can only be employed to probe a single length scale, like the nanometric or the micrometric levels. Moreover, some multiscale systems lack tridimensional order, further reducing the possibilities of investigation.129 Xe nuclear magnetic resonance (NMR) provides a unique and comprehensive description of multiscale porous materials by exploiting the adsorption and diffusion of xenon atoms. NMR parameters like chemical shift, relaxation times, and diffusion coefficient allow the probing of structures from a few angstroms to microns at the same time. Xenon can evaluate the size and shape of a variety of accessible volumes such as pores, layers, and tunnels, and the chemical nature of their surface. The dynamic nature of the probe provides a simultaneous exploration of different scales, informing on complex features such as the relative accessibility of different populations of pores. In this review, the basic principles of this technique will be presented along with some selected applications, focusing on its ability to characterize multiscale materials.

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs’ cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 µg/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.