Metacognition as a mediator of the relation between family SES and language and mathematical abilities in preschoolers.

The effect of family socioeconomic status (SES) on academic achievement in literacy and numeracy has been extensively studied with educational inequalities already witnessed in preschoolers. This is presumably explained by the effect of family SES on cognitive and socioemotional abilities associated with academic achievement. Metacognition which refers to knowledge and regulation skills involving reflexivity about one's own cognitive processes is one of these abilities. However, most of the studies investigating the association between metacognition and academic achievement have focused on school-aged students and studies with younger students are only emerging. Meanwhile, the association between family SES and metacognition abilities has surprisingly received little attention regardless of participants' age. The aim of this study was to explore the associations between family SES, metacognition, language and mathematical abilities in preschoolers aged 5 to 6. We provide the first evidence that the effect of family SES on preschoolers' language and mathematical abilities is mediated by the effect of family SES on their metacognitive abilities. The implications for future research, education and policies aiming at reducing educational inequalities are discussed.

Regeneration and Long-Term Stability of a Low-Power Eco-Friendly Temperature Sensor Based on a Hydrogel Nanocomposite.

A water-processable and low-cost nanocomposite material, based on gelatin and graphene, has been used to fabricate an environmentally friendly temperature sensor. Demonstrating a temperature-dependent open-circuit voltage between 260 and 310 K, the sensor effectively detects subzero ice formation. Notably, it maintains a constant temperature sensitivity of approximately -19 mV/K over two years, showcasing long-term stability. Experimental evidence demonstrates the efficient regeneration of aged sensors by injecting a few drops of water at a temperature higher than the gelation point of the hydrogel nanocomposite. The real-time monitoring of the electrical characteristics during the hydration reveals the initiation of the regeneration process at the gelation point (~306 K), resulting in a more conductive nanocomposite. These findings, together with a fast response and low power consumption in the range of microwatts, underscore the potential of the eco-friendly sensor for diverse practical applications in temperature monitoring and environmental sensing. Furthermore, the successful regeneration process significantly enhances its sustainability and reusability, making a valuable contribution to environmentally conscious technologies.

Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study.

PURPOSE: The intensity of anti-EGFR-based first-line therapy for RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC), once disease control is achieved, is controversial. A de-escalation strategy with anti-EGFR monotherapy represents a potential option to maintain efficacy while reducing cytotoxicity. METHODS: In this multicenter, open-label, phase III trial, patients with untreated RAS/BRAF wt mCRC were randomly assigned to receive either fluorouracil, leucovorin, and irinotecan/cetuximab (FOLFIRI/Cet) until disease progression (arm A) or FOLFIRI/Cet for eight cycles followed by Cet alone (arm B). The coprimary end points were a noninferior progression-free survival (PFS) in the modified per-protocol (mPP) population (>eight cycles) and a lower incidence of grade (G) 3-4 adverse events (AEs) for arm B compared with arm A. RESULTS: Overall, 606 patients were randomly assigned, with 300 assigned to arm A and 306 to arm B. The median follow-up was 22.3 months. In the mPP population, 291 events occurred with a PFS of 10 versus 12.2 months for arms B and A, respectively (P of noninferiority = .43). In the intention-to-treatment (ITT, ≥one cycle) population, 503 events occurred with a PFS of 9 versus 10.7 months (P = .39). The overall survival was 35.7 versus 30.7 months (P = .119) and 31.0 versus 25.2 months (P = .32) in the mPP and ITT population, respectively. Arm B had lower G3-4 AEs during the maintenance period than arm A (20.2% v 35.1%). CONCLUSION: The ERMES study did not demonstrate noninferiority of maintenance with Cet alone. Despite a more favorable safety profile, maintenance with single-agent Cet after induction with FOLFIRI/Cet cannot be recommended for all patients but could represent an option in selected cases.

Mesoscopic 3D Charge Transport in Solution-Processed Graphene-Based Thin Films: A Multiscale Analysis.

Graphene and related 2D material (GRM) thin films consist of 3D assembly of billions of 2D nanosheets randomly distributed and interacting via van der Waals forces. Their complexity and the multiscale nature yield a wide variety of electrical characteristics ranging from doped semiconductor to glassy metals depending on the crystalline quality of the nanosheets, their specific structural organization ant the operating temperature. Here, the charge transport (CT) mechanisms are studied that are occurring in GRM thin films near the metal-insulator transition (MIT) highlighting the role of defect density and local arrangement of the nanosheets. Two prototypical nanosheet types are compared, i.e., 2D reduced graphene oxide and few-layer-thick electrochemically exfoliated graphene flakes, forming thin films with comparable composition, morphology and room temperature conductivity, but different defect density and crystallinity. By investigating their structure, morphology, and the dependence of their electrical conductivity on temperature, noise and magnetic-field, a general model is developed describing the multiscale nature of CT in GRM thin films in terms of hopping among mesoscopic bricks, i.e., grains. The results suggest a general approach to describe disordered van der Waals thin films.

Editorial for Special Issue "Electric Transport and Magnetic Properties in Nanomaterials and Thin Films".

Several nanomaterials and thin films have recently attracted much attention due to their peculiar electric transport and magnetic properties, such as the so-called magnetoresistance effect and the interplay between spin, orbital, charge, and structural degrees of freedom [...].

Low-Power and Eco-Friendly Temperature Sensor Based on Gelatin Nanocomposite.

An environmentally-friendly temperature sensor has been fabricated by using a low-cost water-processable nanocomposite material based on gelatin and graphene. The temperature dependence of the electrochemical properties has been investigated by using cyclic voltammetry, chronopotentiometry and impedance spectroscopy measurements. The simple symmetric device, composed of a sandwich structure between two metal foils and a printable graphene-gelatin blend, exhibits a dependence on the open-circuit voltage in a range between 260 and 310 K. Additionally, at subzero temperature, the device is able to detect the ice/frost formation. The thermally-induced phenomena occur at the electrode/gel interface with a bias current of a few tens of µA. The occurrence of dissociation reactions within the sensor causes limiting-current phenomena in the gelatin electrolyte. A detailed model describing the charge carrier accumulation, the faradaic charge transfer and diffusion processes within the device under the current-controlled has been proposed. In order to increase the cycle stability of the temperature sensor and reduce its voltage drift and offset of the output electrical signal, a driving circuit has been designed. The eco-friendly sensor shows a temperature sensitivity of about -19 mV/K, long-term stability, fast response and low-power consumption in the range of microwatts suitable for environmental monitoring for indoor applications.

Electrical conduction and noise spectroscopy of sodium-alginate gold-covered ultrathin films for flexible green electronics.

Green electronics is an emerging topic that requires the exploration of new methodologies for the integration of green components into electronic devices. Therefore, the development of alternative and eco-friendly raw materials, biocompatible and biodegradable, is of great importance. Among these, sodium-alginate is a natural biopolymer extracted from marine algae having a great potential in terms of transparency, flexibility, and conductivity, when functionalized with a thin gold (Au) layer. The electrical transport of these flexible and conducting substrates has been studied, by DC measurements, from 300 to 10 K, to understand the interplay between the organic substrate and the metallic layer. The results were compared to reference bilayers based on polymethyl-methacrylate, a well-known polymer used in electronics. In addition, a detailed investigation of the electric noise properties was also performed. This analysis allows to study the effect of charge carriers fluctuations, providing important information to quantify the minimum metallic thickness required for electronic applications. In particular, the typical noise behavior of metallic compounds was observed in samples covered with 5 nm of Au, while noise levels related to a non-metallic conduction were found for a thickness of 4.5 nm, despite of the relatively good DC conductance of the bilayer.

Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies.

Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline (n = 37), at 8 weeks of treatment (n = 32), progressive disease (PD; n = 36) and 3 months after PD (n = 21). cfDNA testing was performed using the Idylla™ ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients (p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment.

Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer.

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy.

Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.

BACKGROUND: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. RESULTS: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008). CONCLUSION: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.

Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression.

BACKGROUND: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b ('3 + 3' design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2). RESULTS: In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5-74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%). CONCLUSIONS: Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit-risk balance in sorafenib pretreated aHCC with MET overexpression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02115373.

Electric Transport in Gold-Covered Sodium-Alginate Free-Standing Foils.

The electric transport properties of flexible and transparent conducting bilayers, realized by sputtering ultrathin gold nanometric layers on sodium-alginate free-standing films, were studied. The reported results cover a range of temperatures from 3 to 300 K. In the case of gold layer thicknesses larger than 5 nm, a typical metallic behavior was observed. Conversely, for a gold thickness of 4.5 nm, an unusual resistance temperature dependence was found. The dominant transport mechanism below 70 K was identified as a fluctuation-induced tunneling process. This indicates that the conductive region is not continuous but is formed by gold clusters embedded in the polymeric matrix. Above 70 K, instead, the data can be interpreted using a phenomenological model, which assumes an anomalous expansion of the conductive region upon decreasing the temperature, in the range from 300 to 200 K. The approach herein adopted, complemented with other characterizations, can provide useful information for the development of innovative and green optoelectronics.

Italian results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer.

The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0-1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.

Lay abstract PRECONNECT is an international study demonstrating the efficacy and tolerability of the drug combination trifluridine/tipiracil in adult patients with metastatic colorectal cancer treated in everyday clinical practice. For this publication, the authors conducted an analysis performed on the 161 Italian patients enrolled in this study. These kinds of analyses are important because of the differences that may arise across different countries. The most common contraindications were not dangerous to health. Furthermore, 3 months from beginning the medication, half of the patients did not show a worsening of the disease and quality of life during treatment was maintained. Clinical trial registration: NCT03306394 (ClinicalTrials.gov).

Appropriateness of trifluridine/tipiracil in the clinical practice of third-line therapy in metastatic colorectal cancer.

Aim: To help to remove misperception of an appropriate position of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. Materials & methods: The RAND Corporation/UCLA Appropriateness Method was used by a panel of Italian experts to develop recommendations concerning daily practice with FTD/TPI. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Results: Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, the practice of treatment with FTD/TPI, evaluation and efficacy and toxicity, as well as costs and compliance. Conclusion: FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

Lay abstract To remove misperception of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. An established Method for evaluating appropriateness of new drugs was used. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, efficacy and toxicity, as well as compliance. FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

Magnetotransport and magnetic properties of amorphous [Formula: see text] thin films.

[Formula: see text] is an intermetallic compound with a bulk Curie temperature ([Formula: see text]) of 6-13 K. While existing studies have focused on [Formula: see text] crystals, amorphous thin-films of [Formula: see text] are potentially important since they would be magnetically soft without magnetocrystalline anisotropy, meaning that small external magnetic fields could reverse the direction of their magnetization. Here, we report [Formula: see text] thin-films with a thickness in the 5-200 nm range, deposited by DC magnetron sputtering onto Si(100). Films are amorphous with a weak temperature-dependent resistivity with values ranging between 150 and 300 [Formula: see text] cm. By means of noise spectroscopy, by analyzing the time-dependence of fluctuation-induced voltages, it is found that at low temperatures the resistance fluctuations are due to the Kondo effect. Volume magnetometry indicates [Formula: see text] K with a magnetic coercive field of 30 mT at 5 K for a 125-nm-thick film. The results are promising for the development of Ferromagnet(F)/Superconductor(S)/Ferromagnet(F) pseudo spin-valve devices based on amorphous [Formula: see text] thin films.

Treatment of Locally Advanced Gastric Cancer (LAGC): Back to Lauren's Classification in Pan-Cancer Analysis Era?

Background: Guidelines recommend a perioperative approach in patients with stage II/III gastric cancer, but in real-life many patients receive immediate surgery followed by adjuvant chemotherapy (aCT). Although histologic subtypes may have different response to CT, no study has explored the influence of histotype on the efficacy of perioperative CT (pCT) or aCT. Materials and methods: The objective of the study was to evaluate the impact of clinicopathological features and histology (intestinal or diffuse) on survival according to strategy (pCT vs. aCT). The primary endpoint was overall survival (OS) and the secondary endpoint was event-free survival (EFS). Results: Out of 203 patients affected by LAGC, 83 received pCT and 120 aCT. At multivariate, histology and LVI in pCT cohort and positive resection margin in the aCT influenced both OS and EFS. No difference in EFS and OS was observed in relation to strategy. However, in the intestinal-type of pCT cohort survival outcomes were significantly higher compared to the aCT cohort, whereas in the diffuse-type were significantly worse in patients receiving pCT compared to those receiving aCT. Conclusions: Although retrospective and small-sized, this study suggests that the benefit of pCT might be limited to the intestinal-type. This hypothesis needs to be confirmed in prospective series.

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases.

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88-1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.

Iron-Based Superconducting Nanowires: Electric Transport and Voltage-Noise Properties.

The discovery of iron-based superconductors paved the way for advanced possible applications, mostly in high magnetic fields, but also in electronics. Among superconductive devices, nanowire detectors have raised a large interest in recent years, due to their ability to detect a single photon in the visible and infrared (IR) spectral region. Although not yet optimal for single-photon detection, iron-based superconducting nanowire detectors would bring clear advantages due to their high operating temperature, also possibly profiting of other peculiar material properties. However, there are several challenges yet to be overcome, regarding mainly: fabrication of ultra-thin films, appropriate passivation techniques, optimization of nano-patterning, and high-quality electrical contacts. Test nanowire structures, made by ultra-thin films of Co-doped BaFe2As2, have been fabricated and characterized in their transport and intrinsic noise properties. The results on the realized nanostructures show good properties in terms of material resistivity and critical current. Details on the fabrication and low temperature characterization of the realized nanodevices are presented, together with a study of possible degradation phenomena induced by ageing effects.

Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS: Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. RESULTS: Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly. CONCLUSION: ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.