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The diffusion of lithium ions decoupled from a solid polymer electrolyte matrix is the key for high-energy electrochemical devices with the safety needed for commercial use. This Letter reports how the ion mobility in a single-phase hybrid polyelectrolyte (SPHP) matrix can be tuned by changing an inorganic coordinating atom from silicon (Si) to germanium (Ge). Nuclear Magnetic Resonance (NMR) results show that the lithium ion activation barrier in the polyelectrolyte with Si can be modulated from 0.26 eV to the unprecedented value of 0.12 eV in the polyelectrolyte with Ge. Density functional theory is used to show that the electronic structures of both polymers are very different, although their chemical structures are very similar, except for the coordinating atom. This simple chemical substitution route will certainly increase the interest in these polymers for applications in electrochemical devices.

Hydrocarbon polar metabolites are gaining interest from industry and the remediation community due to their ubiquity and uncertainty around their toxicity. In this study, we used headspace-gas chromatography/mass spectrometry (HS-GC/MS) to characterize polar metabolites present in elutriates derived from uncontaminated, freshly hydrocarbon contaminated and partially remediated Antarctic soils. Elutriates represent the bioavailable fraction and may be used as a proxy for leachate runoff in environmental risk assessments. Control and contaminated soil elutriates were analysed for the presence of 12 aldehydes and two ketones, which cover a broad spectrum of metabolites, ranging from nC2 – nC12 carbon chain length. A total of nine aldehydes were detected in the soil elutriates. Types of aldehydes present in uncontaminated and hydrocarbon contaminated elutriates were similar. Among the polar metabolites measured in elutriates, acetaldehyde was most abundant in partially remediated soils. Microtox assays were used to determine the potential toxicity of elutriates. In addition, three aldehydes that were present at the highest concentrations in the contaminated and partially remediated soil elutriates (acetaldehyde, octanal and undecanal) were tested as single compounds. Contaminated soil elutriates tested were found to be toxic, with partially remediated elutriates less toxic than freshly contaminated elutriates. None of the three aldehydes tested separately were toxic at levels at which they were measured in elutriates. We infer that high levels of acetaldehyde in partially remediated soil due to hydrocarbon degradation highlight the potential of this metabolite as a useful chemical marker for hydrocarbon degradation under certain conditions. Microtox was sensitive to metabolites and provided a useful initial screening tool for elutriates.

We report high room-temperature mobility in single layer graphene grown by Chemical Vapor Deposition (CVD) after wet transfer on SiO$_2$ and hexagonal boron nitride (hBN) encapsulation. By removing contaminations trapped at the interfaces between single-crystal graphene and hBN, we achieve mobilities up to$\sim70000cm^2 V^{-1} s^{-1}$ at room temperature and$\sim120000cm^2 V^{-1} s^{-1}$ at 9K. These are over twice those of previous wet transferred graphene and comparable to samples prepared by dry transfer. We also investigate the combined approach of thermal annealing and encapsulation in polycrystalline graphene, achieving room temperature mobilities$\sim30000 cm^2 V^{-1} s^{-1}$. These results show that, with appropriate encapsulation and cleaning, room temperature mobilities well above $10000cm^2 V^{-1} s^{-1}$ can be obtained in samples grown by CVD and transferred using a conventional, easily scalable PMMA-based wet approach.

Apomictic grasses predominate among tropical forages, and specific breeding techniques are needed for their genetic improvement. The objectives were to: 1- generate hybrids by crossing tetraploid sexual and apomictic Paspalum simplex genotypes, 2- develop a technique based on molecular markers for early identification of apomictic hybrids, and 3- determine the relationship between mode of reproduction and performance of hybrids. Crosses were made between two induced sexual and seven apomictic tetraploid plants. Identification of apomictic hybrids during seedling stage was performed using a marker linked to apomixis, and by flow cytometric seed analysis (FCSA). Hybrids were evaluated under field conditions for plant diameter and height, initial regrowth, and seasonal regrowth during two consecutive growing seasons. Sexual tetraploid plants used as female parents behaved as allogamous since 95% of the progeny had male-specific markers. The ratio between apomictic and sexual hybrids differed among crosses from 1:8.7 and 1:0.6 among crosses, with a mean of 1:2.4. There was a 96% coincidence between the use of the apomixis?linked marker and FCSA. A technique based on the use of an early DNA isolation and the amplification of a molecular marker linked to apomixis was developed. We found no overall difference between apomictic and sexual hybrids for the evaluated traits, except for fall regrowth in the first year, for which apomictic hybrids were superior. Generation of large tetraploid hybrid progenies is possible in P. simplex. Segregation for mode of reproduction depends on parents involved. Agronomic performance is not related to reproductive mode among tetraploid hybrids. Fil: Brugnoli, Elsa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Martínez, Eric Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Ferrari Usandizaga, Silvana Consuelo. Instituto Nacional de Tecnología Agropecuaria; Argentina Fil: Zilli, Alex Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Urbani, Mario Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Acuña, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina

We report for the first time the efficiency and safety of a 49-month compassionate use of the microsomal transfer protein inhibitor lomitapide in a child with homozygous familial hypercholesterolemia. On average, 20 mg of lomitapide caused a 37% reduction in low-density lipoprotein cholesterol levels on top of ezetimibe and atorvastatin. The drug was well tolerated with no changes in liver enzymes and occurrence of steatosis on hepatic ultrasound. The patient presented adequate growth and sexual maturation. Nonetheless, there was progression in either subclinical atherosclerotic carotid or aortic valve diseases. Further studies are necessary to test the impact and safety of lomitapide in children with homozygous familial hypercholesterolemia.

Las ferulas de reposo son dispositivos medicos externos que reducen y limitan la progresion de malformaciones, y calman el dolor y la inflamacion. Se utilizan desde la infancia. Flexibles o rigidas, estandar o moldeables, se aplican con mayor frecuencia en el antepie a las articulaciones metatarsofalangicas e interfalangicas, pero tambien son utiles para mantener posturas antalgicas en el mediopie o la boveda plantar.

Purpose: This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2ndLAARx). Patients and Methods: The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design. The phase II study randomized 55 patients to panobinostat 40 mg (A arm) or 20 mg (B arm) triweekly ×2 weeks with bicalutamide 50 mg/day in 3-week cycles. The primary endpoint was to determine the percentage of radiographic progression-free (rPF) patients at 36 weeks versus historic high-dose bicalutamide. Results: In the model, panobinostat/bicalutamide demonstrated synergistic antitumor effect while reducing AR activity. The dose-limiting toxicity was not reached. The probabilities of remaining rPF were 47.5% in the A arm and 38.5% in the B arm, exceeding the protocol-specified threshold of 35%. The A arm but not the B arm exceeded expectations for times (medians) to rP (33.9 and 10 weeks), and from PSA progression to rP (24 and 5.9 weeks). A arm/B arm events included: adverse events (AE), 62%/19%; treatment stopped for AEs, 27.5%/11.5%; dose reduction required, 41%/4%. The principal A-arm grade ≥ 3 AEs were thrombocytopenia (31%) and fatigue (14%). Conclusions: The 40 mg panobinostat/bicalutamide regimen increased rPF survival in CRPC patients resistant to 2ndLAARx. Panobinostat toxicity was tolerable with dose reductions. Epigenetic HDACI therapy reduces AR-mediated resistance to bicalutamide in CRPC models with clinical benefit in patients. The combination merits validation using a second-generation antiandrogen.

TPS5114 Background: Patients with high-risk scores by Decipher molecular testing after prostatectomy have a 5-year metastasis rate of 28% (Decipher 0.6-0.7) and 38% (Decipher > 0.7), likely due to micrometastatic disease. Clinical trials with intensified systemic treatment are warranted to increase cure rates and address this unmet need. Previous studies of adjuvant androgen deprivation therapy (ADT) in clinically identified high-risk disease have not demonstrated substantial benefit other than in men with lymph node positive disease. Darolutamide is a novel androgen receptor antagonist with demonstrated efficacy in improving metastasis-free survival (MFS) and overall survival (OS) in patients with non-metastatic castration-resistant prostate cancer, and OS in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Whether treatment with ADT and darolutamide can increase MFS versus ADT plus placebo in the adjuvant setting for men with molecularly identified high-risk prostate cancer is unknown. Methods: Patients with CAPRA-S scores ≥3 and a PSA < 0.2 after radical prostatectomy undergo Decipher testing provided by the trial. Eligible patients with high-risk Decipher scores (> 0.6) will be randomized to treatment with ADT with darolutamide or placebo for 12 months. Patients are stratified by intent to deliver adjuvant radiation and by baseline PSA (undetectable vs detectable but < 0.2 ng/mL). The primary endpoint is MFS defined by novel PET or conventional imaging. With a sample size of 810 patients, the trial has 80% power with one-sided alpha = 0.025 to detect a HR of 0.60 for the experimental arm vs control arm for the primary endpoint. Secondary endpoints include recurrence-free survival, event-free survival, and quality of life (FACT-P, FACT-Cog, and FACIT-Fatigue), overall survival, and other disease-related outcomes. Trial was activated on December 9, 2020, and is currently enrolling patients. Clinical trial information: NCT04484818.

This work describes a multilayer tungsten oxide photoanode synthesized via facile dip-coating deposition solution for sunlight-driven water oxidation reaction. The number of layers (three, five and ten) followed by a successive annealing process at each deposited layer has strongly influenced their performance. The ten-layers tungsten oxide photoanode exhibited the highest photocurrent density around 0.7 mA/cm2 at 1.23 VRHE, under sunlight irradiation. This photocurrent response corresponds to 17% of solar-to-hydrogen conversion efficiency (STH) from the maximum theoretical predicted for tungsten oxide (4.8%). The successive annealing treatment promoted a reduction in the number of grain boundaries, yielding in higher film porosity and surface roughness, which decreased the charge transfer resistance and the electron-hole recombination rate.

Candidatus Dormibacterota is an uncultured bacterial phylum found predominantly in soil that is present in high abundances within cold desert soils. Here, we interrogate nine metagenome-assembled genomes (MAGs), including six new MAGs derived from soil metagenomes obtained from two eastern Antarctic sites. Phylogenomic and taxonomic analyses revealed these MAGs represent four genera and five species, representing two order-level clades within Ca. Dormibacterota. Metabolic reconstructions of these MAGs revealed the potential for aerobic metabolism, and versatile adaptations enabling persistence in the 'extreme' Antarctic environment. Primary amongst these adaptations were abilities to scavenge atmospheric H2 and CO as energy sources, as well as using the energy derived from H2 oxidation to fix atmospheric CO2 via the Calvin-Bassham-Benson cycle, using a RuBisCO type IE. We propose that these allow Ca. Dormibacterota to persist using H2 oxidation and grow using atmospheric chemosynthesis in terrestrial Antarctica. Fluorescence in situ hybridization revealed Ca. Dormibacterota to be coccoid cells, 0.3-1.4 μm in diameter, with some cells exhibiting the potential for a symbiotic or syntrophic lifestyle.

Hard disk drives (HDDs) are used as secondary storage in digital electronic devices owing to low cost and large data storage capacity. Due to the exponentially increasing amount of data, there is a need to increase areal storage densities beyond ~1 Tb/in2. This requires the thickness of carbon overcoats (COCs) to be, The main limitation to the areal storage density of hard disk drives (HDDs) is the thickness of carbon overcoats protecting the disk media. Here

Pediatric cancers are not the equivalent of adult cancers occurring at a younger age and the prospect of immunotherapy in children has not been received with the same enthusiasm as in the adult setting. Although most pediatric malignancies are considered immunologically cold, we are learning more about PD-L1 expression, tumor mutational burden, and microsatellite instability in several pediatric cancers. The side effects of immunotherapy are an important consideration. Immune checkpoint inhibitors (ICIs) engender a unique constellation of inflammatory toxicities known as immune-related adverse events (irAEs). Three early-phase trials—KEYNOTE-051, iMATRIX, and ADVL1412—were the first to describe irAEs in pediatric patients and ICIs were well tolerated. There was concern about unknown late irAEs in pediatric patients, as they have much more time to develop than in adult or elderly patients. Academic clinicians, biopharmaceutical companies, and parents’ advocates concluded that no benefit could be expected from further monotherapy trials employing other ICIs with the same mechanism of action until more scientific knowledge becomes available. On the other hand, ICIs could be useful in combination with other therapies to prevent the functional inactivation of several pathways in the hostile microenvironment. Future clinical studies on ICIs in children need to build on strong biological premises, taking into account the distinctive immunobiology of pediatric cancers vis-à-vis ICI-responsive adult cancers. We need to gain and share experiences of new therapies for managing pediatric patients with cancer, clarifying to what extent we can extrapolate the data obtained in adults.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication., Highlights • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.

Monolayer transition metal dichalcogenides with direct bandgaps are emerging candidates for microelectronics, nano-photonics, and optoelectronics. Transferred onto photonic integrated circuits (PICs), these semiconductor materials have enabled new classes of light-emitting diodes, modulators and photodetectors, that could be amenable to wafer-scale manufacturing. For integrated photonic devices, the optical losses of the PICs are critical. In contrast to silicon, silicon nitride (Si3N4) has emerged as a low-loss integrated platform with a wide transparency window from ultraviolet to mid-infrared and absence of two-photon absorption at telecommunication bands. Moreover, it is suitable for nonlinear integrated photonics due to its high Kerr nonlinearity and high-power handing capability. These features of Si3N4 are intrinsically beneficial for nanophotonics and optoelectronics applications. Here we report a low-loss integrated platform incorporating monolayer molybdenum ditelluride (1L-MoTe2) with Si3N4 photonic microresonators. We show that, with the 1L-MoTe2, microresonator quality factors exceeding 3 million in the telecommunication O-band to E-band are maintained. We further investigate the change of microresonator dispersion and resonance shift due to the presence of 1L-MoTe2, and extrapolate the optical loss introduced by 1L-MoTe2 in the telecommunication bands, out of the excitonic transition region. Our work presents a key step for low-loss, hybrid PICs with layered semiconductors without using heterogeneous wafer bonding.

Funder: ERC Grants Hetero2D, Funder: GSYNCOR, Funder: EU Graphene Flagship, Black phosphorous (BP) is a layered semiconductor with high carrier mobility, anisotropic optical response and wide bandgap tunability. In view of its application in optoelectronic devices, understanding transient photo-induced effects is crucial. Here, we investigate by time- and angle-resolved photoemission spectroscopy BP in its pristine state and in the presence of Stark splitting, chemically induced by Cs ad-sorption. We show that photo-injected carriers trigger bandgap renormalization, and a concurrent valence band flattening caused by Pauli blocking. In biased samples, photo-excitation leads to a long-lived (ns) surface photovoltage of few hundreds mV that counterbalances the Cs-induced surface band bending. This allows us to disentangle bulk from surface electronic states, and to clarify the mechanism underlying the band inversion observed in bulk samples.

Multiple studies have reported the observation of electro-synaptic response in different metal/insulator/metal devices; however, most of them analysed large (>1 µm2) devices that do not meet the integration density required by the industry (1010 devices/mm2). Some studies employed a scanning tunnelling microscope (STM) to explore nano-synaptic response in different materials, but in this setup there is a nanogap between the insulator and one of the metallic electrodes (i.e. the STM tip), which is not present in real devices. Here we show how to use a conductive atomic force microscope (CAFM) to explore the presence and quality of nano-synaptic response in confined areas

Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER).

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).

COVID-19 is an ongoing pandemic caused by the highly infectious coronavirus SARS-CoV-2 that is engaging worldwide scientific research to find a timely and effective eradication strategy. Great efforts have been put into anti-COVID-19 vaccine generation in an effort to protect the world population and block SARS-CoV-2 spread. To validate the protective efficacy of the vaccination campaign and effectively control the pandemy, it is necessary to quantify the neutralizing antibodies induction by vaccination, since they have been established to be a correlate of protection. In this work a SARS-CoV-2 pseudovirus neutralization assay, based on a replication incompetent lentivirus expressing an adapted form of CoV-2 S protein and an ACE2/TMPRSS2 stably expressing cell line, have been minimized in term of protocol steps without loss of accuracy. The goal of the present simplified neutralization system is to improve SARS-CoV-2 vaccination campaign by means of an easy and accessible approach to be performed in any medical laboratory, maintaining the sensitivity and quantitative reliability of classical serum neutralization assays. Further this assay can be easily adapted to different coronaviruses variants by simply modifying the pseudotyping vector.

We report room temperature terahertz detection in hBN/graphene/hBN heterostructures. The obtained record combination of high-speed (response time < 1 ns) and high sensitivity (noise equivalent power ~ 100 pWHz-1/2) is enabled by the photo-thermoelectric effect.

Solution-processed semiconducting transition metal dichalcogenides are at the centre of an ever-increasing research effort in printed (opto)electronics. However, device performance is limited by structural defects resulting from the exfoliation process and poor inter-flake electronic connectivity. Here, we report a new molecular strategy to boost the electrical performance of transition metal dichalcogenide-based devices via the use of dithiolated conjugated molecules, to simultaneously heal sulfur vacancies in solution-processed transition metal disulfides and covalently bridge adjacent flakes, thereby promoting percolation pathways for the charge transport. We achieve a reproducible increase by one order of magnitude in field-effect mobility (µFE), current ratio (ION/IOFF) and switching time (τS) for liquid-gated transistors, reaching 10−2 cm2 V−1 s−1, 104 and 18 ms, respectively. Our functionalization strategy is a universal route to simultaneously enhance the electronic connectivity in transition metal disulfide networks and tailor on demand their physicochemical properties according to the envisioned applications. A defect-engineering strategy exploiting dithiolated molecules enables the formation of covalently interconnected networks based on solution-processed transition metal disulfides, leading to devices with enhanced electrical performance and improved characteristics.

Background/objectives The primary aim of this study was to analyse and evaluate the impact of different local treatments on the pattern of relapse in children with primary head and neck non-parameningeal (HNnPM) rhabdomyosarcoma (RMS), treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 study. The secondary aim was to assess whether current risk stratification is valid for this specific site. Design/methods This study includes all patients with localised HNnPM RMS enrolled in the RMS2005 study between 2005 and 2016. Treatment comprised chemotherapy adapted to risk group, with local surgery and/or radiation therapy. The main outcome measures were event-free survival (EFS) and overall survival (OS). Results A total of 165 patients were identified; the median age was 6.4 years (range, 0.1–25). The most common tumour sites were cheek/chin (22%) and nasal ala/nasolabial fold (20%). Histology was unfavourable for 40%, and regional nodal involvement present in 26%. Local therapy included surgery (58%) and/or radiotherapy (72%) to primary tumour and/or regional lymph nodes. After a median follow-up of 66 months (range, 6–158), 42 patients experienced an event, and 17 are still alive. Tumour events were frequent in oral primary (36%), parotid site (26%), cheek/chin (24%), and nasal ala/nasolabial fold (24%) and included locoregional failure in 84% of cases. The 5-year EFS and OS were 75% (95% confidence interval [CI]: 67.3–81.2) and 84.9% (95% CI: 77.5–89.7), respectively. Favourable histology was associated with a better EFS (82.3% versus 64.6%; p = 0.02) and nodal spread with a worse OS (88.6% versus 76.1%; p = 0.04). Different sublocations within the HNnPM primary did not have significant impact on outcome. Conclusion Locoregional relapse/progression is the main tumour failure event in this site. Despite frequent unfavourable risk factors, HNnPM RMS remains a favourable location in the context of a risk-adapted strategy.

As part of the European Union-funded project designated PARTN-ER, the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized non-metastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes e.g. DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor of intermediate malignant potential that predominantly affects children, adolescents and young adults. IMT has a predilection for the lung, abdomen, pelvis, and retroperitoneum, however, can affect any part of the body. IMT is typically localized, and multifocal or metastatic disease is uncommon. Complete surgical resection is the treatment of choice when feasible. There is no established standard of care for unresectable and advanced IMT. Approximately half of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, and fusions involving ROS1, PDGFRβ, RET and NTRK have also been described. Given the molecular landscape of IMT, management of these tumors has evolved to include tyrosine kinase inhibitors and novel targeted therapeutics. This review highlights the molecular characteristics, evolution of targeted therapies and the remaining challenges in the management of IMT.

Background Rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma in childhood, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Adolescents and young adults (AYA) with RMS form a subgroup of patients whose survival lacks behind that of children while diagnosed with histologically similar tumors. Procedures A 67-gene prognostic signature related to chromosome integrity, mitotic control, and genome complexity in sarcomas (CINSARC) is considered a powerful tool for identifying tumors with a highly metastatic potential. With this study, we investigated the prognostic value of CINSARC signature on a cohort of 48 pediatric (PEDs) and AYAs-RMS. Results CINSARC resulted not significantly correlated with age, suggesting other determinants to be responsible for that difference in survival. It remained a significant prognostic variable in both the groups of PEDs and AYAs. Also, genomic grade index signature was tested on the same cohort and showed very similar results with CINSARC. Conclusions Our study showed that CINSARC correlated with outcome in RMS patients and may be potentially considered a tool to predict outcome, and so stratify RMS patients.

ConspectusLaboratory-based experimental astrochemistry regularly entails simulation of astrophysical environments whereby low-temperature condensed ices are exposed to radiation from ultraviolet (UV) photons or energetic charged particles. Here, excited atoms/radicals are generated that are not in thermal equilibrium with their surroundings (i.e., they are nonthermal, or suprathermal). These species can surpass typical reaction barriers and partake in unusual chemical processes leading to novel molecular species. Often, these are uniquely observable under low-temperature conditions where the surrounding ice matrix can stabilize excited intermediates that would otherwise fall apart. Fourier-transform infrared (FTIR) spectroscopy is traditionally utilized to monitor the evolution of chemical species within ices in situ during radiolysis. Yet, the characterization and quantification of novel species and radicals formed within astrophysical ices is often hindered since many of these cannot be synthesized by traditional synthetic chemistry. Computational approaches can provide fundamental vibrational frequencies and isotopic shifts to help aid in assignments alongside infrared intensities and Raman activities to quantify levels of production. In this Account, we begin with a brief history and background regarding the composition and radiation of interstellar ices. We review details of some of the early work on carbon oxides produced during the radiolysis of pure carbon dioxide ices and contention around the carrier of an absorption feature that could potentially be a product of radiation. We then provide an overview of current and emerging experimental methodologies and some of the chemistries that occur via nonthermal processes during radiolysis of low-temperature ices. Next, we detail computational approaches to reliably predict vibrational frequencies, infrared intensities, and Raman activities based on our recent work. Our focus then turns to studies on the formation of complex organics and carbon oxides, highlighting those aided by computational approaches and their role in astrochemistry. Some recent controversies regarding assignments alongside our recent results on the characterization of novel carbon oxide species are discussed. We present an argument for the potential role of carbon oxides within cometary ices as parent molecular species for small volatiles. We provide an overview of some of the complex organic species that can be formed within interstellar and cometary ices that contain either carbon monoxide or carbon dioxide. We examine how Raman spectroscopy could potentially be leveraged to help determine and characterize carbon oxides in future experiments as well as how computational approaches can aid in these assignments. We conclude with brief remarks on future directions our research group is taking to unravel astrochemically relevant carbon oxides using combined computational and experimental approaches.

Background Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. Patients and methods Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Eta Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed. Results Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up. Conclusions Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.

Background: Cancer diagnosis and related treatment can limit young patients’ privacy. Their need for private physical and psychological spaces can be impeded by limited freedom, e.g., sharing hospital rooms with others and exposing their body to their parents and doctors. Methods: We conducted a survey among young patients of our center to investigate how their perception of privacy changed after being diagnosed with cancer and their need for hospital dedicated physical spaces and time for patients to enjoy their privacy. A questionnaire with 16 items was developed by the staff involving psychologists and physicians. The relevance of changes before and after the cancer diagnosis was assessed by calculating two scores indicating the situation before and after diagnosis for each answer, as well as a delta score. Results: Between May and June 2020, the questionnaire was completed by 60 patients aged 16–24 years. The median delta scores describing the changes before and after diagnosis were −8 points for perception of privacy, indicating a significant decrement of the level of privacy perceived. A major issue was the constant presence of parents being perceived as intrusive. Concerning hospital dedicated physical spaces and time for patients to enjoy their privacy, respondents requested dedicated spaces (50% of patients) and opportunities to have private interviews with medical personnel (88%). Conclusions: Our study offers a snapshot of how young people with cancer perceive the impact of the disease and its treatment on their privacy with the restrictions imposed on their individual freedom. Patients’ personal needs must be taken into consideration to adopt appropriate measures and better organize wards.

Batteries that extend performance beyond the intrinsic limits of Li-ion batteries are among the most important developments required to continue the revolution promised by electrochemical devices. Of these next-generation batteries, lithium sulfur (Li–S) chemistry is among the most commercially mature, with cells offering a substantial increase in gravimetric energy density, reduced costs and improved safety prospects. However, there remain outstanding issues to advance the commercial prospects of the technology and benefit from the economies of scale felt by Li-ion cells, including improving both the rate performance and longevity of cells. To address these challenges, the Faraday Institution, the UK’s independent institute for electrochemical energy storage science and technology, launched the Lithium Sulfur Technology Accelerator (LiSTAR) programme in October 2019. This Roadmap, authored by researchers and partners of the LiSTAR programme, is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the LiSTAR consortium. In compiling this Roadmap we hope to aid the development of the wider Li–S research community, providing a guide for academia, industry, government and funding agencies in this important and rapidly developing research space.

BackgroundThe analysis of blow microbiota has been proposed as a biomarker for respiratory health analysis in cetaceans. Yet, we lack crucial knowledge on the long-term stability of the blow microbiota and its potential changes during disease. Research in humans and mice have provided evidence that respiratory disease is accompanied by a shift in microbial communities of the airways. We investigate here the stability of the community composition of the blow microbiota for 13 captive bottlenose dolphins over eight months including both sick and healthy individuals. We used barcoded tag sequencing of the bacterial 16S rRNA gene. Four of the dolphins experienced distinct medical conditions and received systemic antimicrobial treatment during the study.ResultsWe showed that each dolphin harboured a unique community of zero-radius operational taxonomic units (zOTUs) that was present throughout the entire sampling period (‘intra-core’). Although for most dolphins there was significant variation over time, overall the intra-core accounted for an average of 73% of relative abundance of the blow microbiota. In addition, the dolphins shared between 8 and 66 zOTUs on any of the sampling occasions (‘inter-core’), accounting for a relative abundance between 17 and 41% of any dolphin’s airway microbiota. The majority of the intra-core and all of the inter-core zOTUs in this study are commonly found in captive and free-ranging dolphins and have previously been reported from several different body sites. While we did not find a clear effect of microbial treatment on blow microbiota, age and sex of the dolphins did have such an effect.ConclusionsThe airways of dolphins were colonized by an individual intra-core ‘signature’ that varied in abundance relative to more temporary bacteria. We speculate that the intra-core bacteria interact with the immune response of the respiratory tract and support its function. This study provides the first evidence of individual-specific airway microbiota in cetaceans that is stable over eight months.

While the tin-vacancy center in diamond (SnV) has demonstrated excellent optical properties [1], spin control has remained elusive. We demonstrate multi-axis control of the SnV spin via an all-optical drive, and use this to demonstrate T2 = 0.30(8) ms.

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This article reviews the primary goals and achievements of the Italian Association for Pediatric Hematology-Oncology (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]), a national cooperative group that has been working for children and adolescents with cancer in Italy since 1975.

Graphene possesses a peculiar potential for the development of optoelectronic components capable to actively manipulate infrared light [1] . Its electrostatically tunable optical conductivity, band structure and transport characteristics, and the possibility to be grown over large areas, offer an intriguing playground for engineering, at the nanoscale, amplitude modulators, spatial light modulators and switches, combining high efficiency (> 50%) intensity modulation, reasonably high speeds (> s response times), and spectral tunability in the underexploited high (> 1.5 THz) terahertz-frequency range [2] , where frontier applications in quantum communications, quantum computing, adaptive and quantum optics are still at their infancy.

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases.

As part of the European Union-funded project designated Paediatric Rare Tumours Network - European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.

Group-IV color centers in diamond are a promising light-matter interface for quantum networking devices. The negatively charged tin-vacancy center (SnV) is particularly interesting, as its large spin-orbit coupling offers strong protection against phonon dephasing and robust cyclicity of its optical transitions toward spin-photon-entanglement schemes. Here, we demonstrate multiaxis coherent control of theSnVspin qubit via an all-optical stimulated Raman drive between the ground and excited states. We use coherent population trapping and optically driven electronic spin resonance to confirm coherent access to the qubit at 1.7K and obtain spin Rabi oscillations at a rate ofΩ/2π=19.0(1)  MHz. All-optical Ramsey interferometry reveals a spin dephasing time ofT∗2=1.3(3)  μs, and four-pulse dynamical decoupling already extends the spin-coherence time toT2=0.30(8)  ms. Combined with transform-limited photons and integration into photonic nanostructures, our results make theSnVa competitive spin-photon building block for quantum networks.

The Muon g−2 Experiment at Fermi National Accelerator Laboratory (FNAL) has measured the muon anomalous precession frequency ωma to an uncertainty of 434 parts per billion (ppb), statistical, and 56 ppb, systematic, with data collected in four storage ring configurations during its first physics run in 2018. When combined with a precision measurement of the magnetic field of the experiment’s muon storage ring, the precession frequency measurement determines a muon magnetic anomaly of aμ(FNAL)=116592040(54)×10−11 (0.46 ppm). This article describes the multiple techniques employed in the reconstruction, analysis, and fitting of the data to measure the precession frequency. It also presents the averaging of the results from the 11 separate determinations of ωma, and the systematic uncertainties on the result.

Purpose: Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study desc...

BEaTriX (Beam Expander Testing X-ray) is the X-ray facility under construction at the INAF-Osservatorio Astronomico Brera (Merate, Italy) to prove that it is possible to perform the X-ray acceptance tests (PSF and Aeff) of the ATHENA mirror modules at the required rate and with the required accuracy. The unique optical setup makes use of a micro-focus X-ray source with anode in Titanium, a paraboloidal mirror with small radius of curvature, and a set of crystals to monochromate and expand the beam to fully illuminate the entrance pupil of the ATHENA MMs. The quality of the optical components, and their precise alignment, guarantees the production of a parallel beam at 4.51 keV, to be extended in a second phase to 1.49 keV in order to complete the acceptance requirements for the ATHENA MMs. The completion of the facility is expected to occur in July this year, while the commissioning will start in September. In this paper, we present the current status.

L’emergenza pandemica ha riproposto con forza il tema dei diritti fondamentali e dell’intervento pubblico per la loro garanzia, che deve essere ricollegato ad una necessaria rilettura della sovranità, finalmente disancorata dall’ancoraggio esclusivo ed assorbente alla rappresentanza popolare. La sovranità, come delineata dalla Costituzione italiana, significa anche funzionalizzazione dell’autorità ai diritti della persona e, quindi, sguardo non neutrale e proattivo rispetto alla necessaria garanzia dei diritti fondamentali. Da questa premessa concettuale, che ha innervato il dibattito promosso da PA Persona e Amministrazione, i componenti della Direzione della Rivista hanno avviato e promosso un’analisi della reazione europea e nazionale all’emergenza pandemica nella prospettiva tematica delle disuguaglianze ingiuste e dell’individuazione degli strumenti giuridici per il loro superamento, a partire dall'occasione offerta dal PNRR.

We present Z-Type Dye Sensitized Solar Modules (DSSMs) with screen printed graphene-based vertical interconnects. This prevents corrosion of interconnects in contact with electrolytic species, unlike conventional Ag interconnects. By enlarging the width of single cells, or by increasing the number of cells, we get an enhancement of the aperture power conversion efficiency ∼+12% with respect to Ag-based modules, with 1000 h stability under 85 °C stress test. This paves the way to original design layouts with decreased dead area and increased generated power per aperture area.

Electron transport across the transition-metal dichalcogenide (TMD)/metal interface plays an important role in determining the performance of TMD-based optoelectronic devices. However, the robustness of this process against structural heterogeneities remains unexplored, to the best of our knowledge. Here, we employ a combination of time-resolved photoemission electron microscopy (TR-PEEM) and atomic force microscopy to investigate the spatially resolved hot-electron-transfer dynamics at the monolayer (1L) MoS

Transition metal dichalcogenides (TMDs) have rapidly emerged as one of the most attractive families of two-dimensional materials due to their numerous outstanding electronic and optoelectronic properties. TMDs have layer-dependent band structures, exhibiting a dramatic transition from a direct bandgap in the monolayer (1L) to an indirect bandgap in the multilayer (NL). TMD homojunctions form when a 1L TMD interfaces with an NL TMD of the same chemical composition. Such 1L/NL TMD homojunctions are predicted to have similar properties as heterojunctions, which comprises two different TMDs. In this work, we employ time-resolved photoemission electron microscopy (TR-PEEM) to study the ultrafast carrier dynamics of a WSe2 1L/NL Type-I homojunction with high temporal (50 fs) and spatial (70 nm) resolution. Published version