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Arterial ischemic stroke (AIS) in children has a high mortality and life-long disability rate in surviving patients. Diagnostic delays are longer and risk factors are different compared with AIS in the adult population. Congenital heart disease, cervical arterial dissection, and intracranial arteriopathies are the main causes of AIS in children. New revascularization time windows in children require the definition of diagnostic protocols for stroke in each referral center. In this article, we discuss the neuroimaging techniques and protocols, describe the main underlying causes, and review the current treatment options for pediatric and perinatal AIS.

In view of wide-ranging application to the biomedical field, this work investigates the mechanical and electrical properties of a composite made of Single Wall Carbon Nanotubes (SWCNT) bundles self-grafted onto a poly-dimethyl-siloxane (PDMS) elastomer, particularly Sylgard 184, that has well assessed biocompatible properties and is commonly used in prosthetics. Due to the potential risks associated with the use of carbon nanostructures in implanted devices, we also assess the viability of cells directly grown on such composite substrates. Furthermore, as the stability of conductive, stretchable devices made of such composite is also crucial to their use in the medical field, we investigate, by different experimental techniques, the grafting of SWCNT bundles deep into PDMS films. Our findings prove that penetration of SWCNT bundles into the polymer bulk depends on heating time and carbon nanotubes can be seen beyond 150 μm from the surface. This is confirmed by direct electron microscopy observation of large bundles as deep as about 20 μm. The composites exhibit reliable mechanical and electrical responses that are more suitable to large and repeated deformation of the polymer with respect to thermoplastic based composites, suggesting a wide potential for their application to stretchable biomedical devices. Aiming at the proposed application of artificial bladders, a bladder prototype made of poly-dimethyl siloxane endowed with a printed SWCNT-based strain sensor was developed.

Biometric systems are largely based on Machine Learning (ML) algorithms which are often considered as a black-box. There is a need to provide them with explanations to make their decision understandable. In this paper, we conduct a Systematic Literature Review aiming at investigating the present adoption of explainable Artificial Intelligence (XAI) techniques in biometric systems. By examining the biometric tasks performed by the selected papers (e.g., face detection or face spoofing), the datasets adopted by the different approaches, the considered ML models, the XAI techniques, and their evaluation methods. We started from 496 papers and, after an accurate analysis, selected 47 papers. Results revealed that XAI is mainly adopted in biometric systems related to the face biometric cues. The explanations provided were all based on model-centric metrics and did not consider how the end-users perceived the explanations, leaving wide space for the biometric researchers to apply the XAI models and enhance the explanation evaluation into an HCI perspective.

Abstract: We report the results of a controlled experiment and a replication performed with different subjects, in which we assessed the usefulness of an Information Retrieval-based traceability recovery tool during the traceability link identification process. The main result achieved in the two experiments is that the use of a traceability recovery tool significantly reduces the time spent by the software engineer with respect to manual tracing. Replication with different subjects allowed us to investigate if subjects’ experience and ability play any role in the traceability link identification process. In particular, we made some observations concerning the retrieval accuracy achieved by the software engineers with and without the tool support and with different levels of experience and ability.

Background: Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy. Objective: This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer. Methods: We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects. Conclusions: This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.

Chirality is ubiquitous in nature across all length scales, with major implications spanning fields from biology, chemistry and physics to materials science. How chirality propagates from nanoscale building blocks to meso- and macroscopic helical structures remains an open issue. Here, working with a canonical system of filamentous viruses, we demonstrate that their self-assembly into chiral liquid crystal phases quantitatively results from the interplay between two main mechanisms of chirality transfer: electrostatic interactions from the helical charge patterns on the virus surface, and fluctuation-based helical deformations leading to viral backbone helicity. Our experimental and theoretical approach provides a comprehensive framework for deciphering how chirality is hierarchically and quantitatively propagated across spatial scales. Our work highlights the ways in which supramolecular helicity may arise from subtle chiral contributions of opposite handedness that act either cooperatively or competitively, thus accounting for the multiplicity of chiral behaviours observed for nearly identical molecular systems.

Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2–1.0) cm and 2.4 (1.7–3.1) cm respectively with a mean 3,4-fold increase (p< 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were −4.0 (−5.4–−2.1) SDS and 0.1 (−1.9–1.4) SDS respectively (p< 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p= 0.219). Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.

Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine.

Scopo della presente linea guida (LG) è produrre raccomandazioni operative per il trattamento dei pazienti adulti (>18 anni) con adenoma ipofisario prolattino (PRL)-secernente, sulla base delle evidenze disponibili e nel rispetto delle preferenze del paziente, valutando l’ambito e il consumo di risorse per la contestualizzazione più appropriata nel Servizio Sanitario Nazionale (SSN). La finalità è migliorare e standardizzare il trattamento del prolattinoma, in base all’evidenza dei dati di letteratura analizzata secondo il metodo GRADE, offrendo ai pazienti la possibilità della migliore cura su tutto il territorio nazionale. Il presente documento prende in esame le opzioni di trattamento per l’adenoma ipofisario PRL-secernente nell’adulto. Non verranno qui considerati i casi che riguardano i minori di 18 anni, le donne in gravidanza o durante l’allattamento, le forme familiari e gli adenomi ipofisari a secrezione pluri-ormonale. Il beneficio atteso da questa LG è il miglioramento della qualità delle cure e l’omogeneizzazione delle stesse su tutto il territorio nazionale. La popolazione di pazienti adulti con prolattinoma è il target della presente LG, che mira a definire i tempi e le modalità terapeutiche più opportune per la loro gestione clinica. Le preferenze dei pazienti sono state indagate nella letteratura e verificate mediante la partecipazione al gruppo di elaborazione della LG di un paziente. La presente LG è destinata a medici e operatori sanitari coinvolti nella gestione clinica dei pazienti con prolattinoma, in particolare specialisti in endocrinologia del territorio e di centri di 2° livello, medici di medicina generale (MMG), neurochirurghi, ginecologi. La LG è, inoltre, un riferimento per le Associazioni dei Pazienti, per raggiungere una corretta informazione sullo stato dell’arte nella gestione del prolattinoma. Gli interventi terapeutici oggetto della LG si attuano a livello ambulatoriale e ospedaliero.

Zeolitic Imidazolate Frameworks (ZIF) find application in storage and dissipation of mechanical energy. Their distinctive properties linked to their (sub)nanometer size and hydrophobicity allow for water intrusion only under high hydrostatic pressure. Here we focus on the popular ZIF-8 material investigating the intrusion mechanism in its nanoscale cages, which is the key to its rational exploitation in target applications. In this work, we used a joint experimental/theoretical approach combining in operando synchrotron experiments during high-pressure intrusion experiments, molecular dynamics simulations, and stochastic models to reveal that water intrusion into ZIF-8 occurs by a cascade filling of connected cages rather than a condensation process as previously assumed. The reported results allowed us to establish structure/function relations in this prototypical microporous material, representing an important step to devise design rules to synthesize porous media.

Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer.

Introduction: US National Cancer Institute’s (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients.Methods: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135).Results: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94).Discussion: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.

Cannabichromene (CBC, 1a) occurs in Cannabis (Cannabis sativa) as a scalemate having a composition that is strain-dependent in terms of both enantiomeric excess and enantiomeric dominance. In the present work, the chirality of CBC (1a), a noncrystalline compound, was shown not to be significantly affected by standard conditions of isolation and purification, and enantiomeric self-disproportionation effects were minimized by carrying out the chiral analysis on crude fractions rather than on purified products. A genetic basis for the different enantiomeric state of CBC in Cannabis therefore seems to exist, implying that the chirality status of natural CBC (1a) in the plant is associated with the differential expression of CBCA-synthase isoforms and/or of associated directing proteins with antipodal enantiospecificity. The biological profile of both enantiomers of CBC should therefore be investigated independently to assess the contribution of this compound to the activity of Cannabis preparations.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos’s along-track orbital velocity component of 2.70 ± 0.10 mm s−1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m−3, we find that the expected value of the momentum enhancement factor, β, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m−3, β=3.61−0.25+0.19(1σ). These βvalues indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAScodon G12 (KRASG12) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAFmutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (n= 800 patients) and found that KRASG12mutations (n= 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P= 0.0031, adjusted interaction P= 0.015). For patients with KRASG12mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (n= 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73–1.20; P= 0.85). In contrast, patients with KRASG13mutant tumors showed significantly improved OS with FTD/TPI versus placebo (n= 60; HR = 0.29; 95% CI = 0.15–0.55; P< 0.001). In isogenic cell lines and patient-derived organoids, KRASG12mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies.

Molecular contact doping in organic field-effect transistors (OFETs) has been proved to be a very efficient strategy to reduce the device contact resistance. It consists of inserting a dopant layer between the organic semiconductor (OSC) and the top gold contacts to reduce the energy barrier required to inject/release charges. However, a main bottle-neck for its implementation is that the dopant diffuses toward the OFET channel with time, doping the OSC, and hampering the on/off switching device capability. In this work, we fabricated OFETs based on the benchmark OSC 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT-C8) by a solution shearing technique. First, we show that the OFET performance of these devices is significantly improved when a layer of the p-dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) is inserted before the evaporation of the gold source/drain contacts. Remarkably, we demonstrate that the dopant diffusion can be controlled by blending the OSC with polystyrene (PS) of different molecular weights. In-depth electrical characterization combined with studies of surface and in-depth distribution of the dopant by time-of-flight secondary ion mass spectrometry (ToF-SIMS) unambiguously show that in thin films of OSC blends with high-molecular-weight PS, the dopant remained drastically confined into the contact areas, which was reflected by an enhanced long-term device stability.

Despite their considerable practical and biological applications, the link between molecular properties, assembly conditions, and self-organized structure in confined polymer solutions remains elusive. Here, we explore the lyotropic nematic ordering of semiflexible chains in spherical confinement for multiple contour lengths across a wide regime of concentrations. We uncover an original crossover from two distinct quadrupolar states, both characterized by regular tetrahedral patterns of surface topological defects, to either longitudinal, latitudinal, or spontaneously twisted bipolar structures with increasing densities. These transitions, along with the intermediary arrangements that they involve, are attributed to the combination of orientational wetting with subtle variations in their liquid-crystal (LC) elastic anisotropies. Our molecular simulations are corroborated by density functional calculations, and are quantified through the introduction of several order parameters as well as an unsupervised learning scheme for the localization of topological defects. Our results agree quantitatively with the predictions of continuum nematic elasticity theories and evidence the extent to which the folding of macromolecules and the self-assembly of low-molecular-weight LCs may be guided by the same, universal principles.

Metastatic urothelial carcinoma (mUC) is a lethal disease for which platinum-based chemotherapy represents the standard of care; however, long-term survival is achieved only in a minority of patients. Recently, along with important advances in the comprehension of the biology of this disease, the treatment paradigm of mUC has undergone a rapid expansion with the approval of several immune-checkpoint inhibitors (ICIs) and targeted agents in both first- and second-line settings. Cisplatin-based chemotherapy remains the backbone of first-therapy for mUC; nevertheless, for those patients who do not progress after the full course of first-line chemotherapy, maintenance treatment with the anti-PD-L1 avelumab showed to prolong overall survival compared observation alone. Moreover, the disappointing results of chemotherapy in pre-treated patients have led to the investigation and the subsequent approval of the anti-PD-1 pembrolizumab, which showed an unprecedented survival benefit when compared to second-line chemotherapy. Recently, target therapy with the antibody-drug conjugate (ADC) enfortumab vedotin, directed against Nectin-4, showed outstanding results in patients treated with both chemotherapy and immunotherapy. The FGFR inhibitor erdafitinib and sacituzumab govitecan, an ADC targeting Trop-2, demonstrated encouraging activity in phase II studies and are currently under investigation in randomized phase III trials. ICIs and targeted therapies also demonstrated promising results as first-line treatment of cisplatin-ineligible patients; randomized trials of ICIs alone or in combination with targeted agents are ongoing and may broaden the therapeutic armamentarium for this category of patients. In this review, we describe the current state of art for the treatment of mUC; in addition, we present the latest evidences from the most recent literature and congress presentations. Finally, we illustrate the key ongoing clinical trials, focusing on ICIs and target therapies.

Immune checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care in metastatic renal cell carcinoma (mRCC), but their activity on the primary tumor is still one of the most debated issues.