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The main source of systematic uncertainty on neutrino cross section measurements at the GeV scale is represented by the poor knowledge of the initial flux. The goal of cutting down this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls (tagger), while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. This instrumentation can provide a full control on both the muon and electron neutrino fluxes at all energies. Furthermore, the narrow momentum width (<10%) of the beam provides a O(10%) measurement of the neutrino energy on an event by event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and is cast in the framework of the CERN neutrino platform (NP06) and the Physics Beyond Colliders initiative. In our contribution, we summarize the ENUBET design, physics performance and opportunities for its implementation in a timescale comparable with next long baseline neutrino experiments.

The NESSiE experiment is designed to perform an accurate measurement of muon-neutrino disappearance at small L/E, in order to severely constrain models with more than three-standard neutrinos, or even determine for the first time the presence of a new kind of neutrino oscillation. NESSiE is a Short-Baseline experiment with magnetic spectrometers at two different sites on the FNAL-Booster neutrino beam. The experiment would allow to definitively solve the existing tension of the muon-neutrino disappearance result with the appearance and disappearance \"anomalies\" at eV mass scale, by spanning one more order of magnitude in the mixing angle between standard and sterile neutrinos. We demonstrate that this project constitutes the most robust and fast way to unambigously study the neutrino physics at that scales.

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80 hi CD115 hi C3aR hi CD88 hi ), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80 + HO-1 + bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1–CSF1R–C3aR axis. Inhibition of F4/80 + HO-1 + TAM recruitment or myeloid-specific deletion of HO-1 blocks metastasis formation and improves anticancer immunotherapy. Relative expression of HO-1 in peripheral monocyte subsets, as well as in tumor lesions, discriminates survival among metastatic melanoma patients. Overall, these results identify a distinct cancer-induced HO-1 + myeloid subgroup as a new antimetastatic target and prognostic blood marker. Tumor-associated macrophages (TAMs) play multifaceted roles in establishing an immunosuppressive tumor microenvironment. Sica and colleagues find that macrophage-intrinsic complement signaling initiates a pathway leading to the induction of highly tumorigenic TAMs.

Halyomorpha halys, (the brown marmorated stink bug, BMSB), is a high-concern invasive species causing severe damage to orchards in many countries outside its native Asian range. Control options matching both effectiveness and sustainability are currently lacking. Inhibitors of chitin biosynthesis might be exploited for integrated management programs because of the overall better ecotoxicological profile in comparison with most neurotoxic insecticides used so far against BMSB. In this study, the activity of triflumuron, a benzoylphenyl urea hampering chitin biosynthesis, was tested on BMSB in laboratory and field conditions. In laboratory bioassays, the insecticide was sprayed on potted peach plants (30 cm high) and residues were aged in a glasshouse for 0, 7, 14, and 21 d. Then, third-instar bugs were placed on the plants and continuously exposed to residues. Mortality was scored after 7, 14, and 21 d exposure.Triflumuron caused significantly higher mortality on BMSB nymphs in comparison with water controls at all aging periods. Moreover, aging of residues up to 21 d did not cause any significant reduction of activity. Field experiments were also carried out in 2019 in eight pear orchards. Injuries to fruits at harvest were compared between plots where triflumuron was added to insecticide sprays against BMSB and control plots managed exactly in the same way but without any triflumuron treatment. An overall mean of 9.99 ± 1.98% stink bug injured fruits was detected in plots managed with the strategy including triflumuron, whereas 19.45 ± 3.55% of fruits were injured in plots assigned to controls.

Background Liquid biopsy has the potential to monitor biological effects of treatment. KRAS represents the most commonly mutated oncogene in Caucasian non-small-cell lung cancer (NSCLC). The aim of this study was to explore association of dynamic plasma KRAS genotyping with outcome in advanced NSCLC patients. Methods Advanced NSCLC patients were prospectively enrolled. Plasma samples were collected at baseline (T1), after 3 or 4 weeks, according to treatment schedule (T2) and at first radiological restaging (T3). Patients carrying KRAS mutation in tissue were analysed in plasma with droplet digital PCR. Semi-quantitative index of fractional abundance of mutated allele (MAFA) was used. Results KRAS -mutated cohort included 58 patients, and overall 73 treatments ( N  = 39 chemotherapy and N  = 34 immune checkpoint inhibitors) were followed with longitudinal liquid biopsy. Sensitivity of KRAS detection in plasma at baseline was 48.3% (95% confidence interval (CI): 35.0–61.8). KRAS mutation at T2 was associated with increased probability of experiencing progressive disease as best radiological response (adjusted odds ratio: 7.3; 95% CI: 2.1–25.0, p  = 0.0016). Increased MAFA (T1–T2) predicted shorter progression-free survival (adjusted hazard ratio (HR): 2.1; 95% CI: 1.2–3.8, p  = 0.0142) and overall survival (adjusted HR: 3.2; 95% CI: 1.2–8.4, p  = 0.0168). Conclusions Longitudinal analysis of plasma KRAS mutations correlated with outcome: its early assessment during treatment has great potentialities for monitoring treatment outcome in NSCLC patients.

IntroductionThe aims of the PROBIT trial (clinicaltrials.gov: NCT03131284) were to prevent overweight or obesity occurring at two years of life, and improve feeding patterns during infancy.MethodsThe trial compared 252 northern Italian newborns whose paediatricians offered their parents an educational programme from the child’s birth to the age of two years (intervention arm) with 216 newborns whose parents did not undergo the programme (control arm). This sample size was 80% powerful to detect, with a 0.05 α error, a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm. At each well visit, the parents of the children in the intervention arm were given oral and written information about protective behaviours, with particular emphasis on responsive feeding. Overweight and obesity at two years of age were, respectively, defined as a body mass index of more than the 85th and the 95th percentile in accordance with the WHO growth charts. The sample size had 80% power to detect a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm.ResultsAt the age of two years, the prevalence of obesity in the intervention arm was 35% lower than among the controls, but the difference was not statistically significant (8.7% vs. 13.4%; p = 0.10) There was no difference in the prevalence of overweight/obesity between the groups (26.8% vs. 28.3%; p = 0.49). At the age of three months, a higher proportion of the infants in the intervention group were fed on demand (93% vs. 80%, p < 0.001).ConclusionsThe PROBIT trial failed to detect a significantly lower prevalence of obesity in the intervention arm, but did improve early feeding patterns. More powerful trials and meta-analyses are required to establish whether educating newborns’ parents can decrease the prevalence of early obesity.

Background Tumor-Associated Macrophages (TAMs) are the main immune component of the tumor stroma with heterogeneous functional activities, predominantly suppressing the immune response and promoting tumor progression, also via secretion of different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated with disease progression in several tumor types. Malignant pleural mesothelioma (MPM) a severe neoplasia with poor prognosis, is characterized by an abundancy of TAMs, testifying the presence of a long-lasting inflammation which is pathogenetic of the disease. However, the role of GPNMB in MPM is unclear. Methods Clinical samples from patients with MPM were used to measure RNA and protein levels of GPNMB. The functional role of GPNMB in vivo was studied in an orthotopic mouse model of mesothelioma using the murine cell lines AB1 and AB22. Experiments included in vivo tumor growth in wild type and in GPNMB-deficient mice and blocking of GPNMB-induced signaling with anti-CD44 antibodies. Results We show that in human and murine MPM tissues the protein GPNMB is mainly produced by infiltrating TAMs. Gpnmb RNA levels in MPM patients from TCGA are significantly associated with lower survival. Using an orthotopic mouse model of mesothelioma we observed that in GPNMB-defective mice (DBA2/J mice) unable to produce the protein, tumors formed by AB1 and AB22 mesothelioma cells grow significantly less than in GPNMB-proficient mice (DBA2/J-Gpnmb+ mice), indicating that host GPNMB is involved in tumor progression. Likewise, the ectopic expression of GPNMB in AB1 and AB22 cells causes an acceleration of tumor growth in vivo, significantly different compared to mock-transduced cells. Treatment of tumor-bearing mice with blocking anti-CD44 (a major receptor for GPNMB) results in a significant reduction of tumor growth. Conclusions Overall, these results indicate that the protein GPNMB, a product and marker gene of TAMs, is a driver of mesothelioma progression and may constitute a promising therapeutic target.

According to the inhibition deficit hypothesis, the ability to inhibit unwanted or irrelevant thoughts and behaviors decreases with age, which can have a significant impact on cognitive and emotional processing. However, studies examining inhibition and age have shown mixed results, with some studies finding a decrease in inhibitory control as individuals age, while others have found no relationship. The goal of this proof-of-concept study was to examine the underlying neural mechanisms that may explain why some older adults are better than others at inhibitory control by investigating the relationship between resting-state functional connectivity (rsFC) of the salience network, a network critical for detecting and focusing attention toward relevant stimuli while ignoring irrelevant information in the environment, and a behavioral measure of inhibitory control (Stroop Task interference score) in a sample of 65 healthy older individuals (ages 65+). Results revealed no direct effect of age on Stroop performance; however, there was an indirect effect of age on Stroop performance through rsFC. These results suggest that rsFC of the salience network may be an important factor to consider when it comes to understanding individual differences in inhibitory control behavior among older adults.

Here, we show that an α-proteobacterium of the genus Asaia is stably associated with larvae and adults of Anopheles Stephensi, an important mosquito vector of Plasmodium vivax, a main malaria agent in Asia. Asaia bacteria dominate mosquito-associated microbiota, as shown by 16S rRNA gene abundance, quantitative PCR, transmission electron microscopy and in situ-hybridization of 16S rRNA genes. In adult mosquitoes, Asaia sp. is present in high population density in the female gut and in the male reproductive tract. Asaia sp. from An. stephensi has been cultured in cell-free media and then transformed with foreign DNA. A green fluorescent protein-tagged Asaia sp. strain effectively lodged in the female gut and salivary glands, sites that are crucial for Plasmodium sp. development and transmission. The larval gut and the male reproductive system were also colonized by the transformed Asaia sp. strain. As an efficient inducible colonizer of mosquitoes that transmit Plasmodium sp., Asaia sp. may be a candidate for malaria control.

Background/Objectives: The child and adolescent mental health service (CAMHS) hand-over to adult mental health service (AMHS) remains an ongoing shortfall in eating disorder (ED) treatment, typically in tandem with diagnostic drift, heightened suicide risk, and carer burn-out. We created one 14-to-25 Transition—ED track within our own unit, where a single multidisciplinary team continuously follows each patient and family across the CAMHS–AMHS boundary (via weekly joint paediatric and adult clinician meeting) without changing the individual psychotherapist, family therapist, or dietitian at the age 18 transition. We investigated the manner in which patients and parents perceive this model. Methods: A survey of two naturalistic parent cohorts—CAMHS (n = 16) and Transition—Adult arm (n = 15)—also joined, alongside the original group of young adults who had entered the programme during its set-up phase (n = 9). Here, the 14–25 pathway denotes one unified route of care across adolescence and young adulthood; the Transition—Adult arm is its ≥ 18-years component. All index patients had a primary DSM-5-TR diagnosis of restricting-type anorexia nervosa. Participants completed the Client Satisfaction Questionnaire-8 (CSQ-8; range 8–32) and four bespoke Continuity-of-Care items (1–4 Likert). Results: Overall, the caregivers in both cohorts were pleased (median CSQ-8 = 28.5 [CAMHS] vs. 27.0 [Transition]; p = 0.75). Continuity items were universally well rated across cohorts. Cohort parents reported a median of two unchanged core clinicians (i.e., the individual psychotherapist, the family therapist, or the dietitian), which was nonsignificantly positively correlated with CSQ-8 scores (ρ = 0.22). Early-group patients mirrored caregiver impressions (mean CSQ-8 = 27.0 ± 3.9). Conclusions: It is feasible and highly acceptable to both caregivers and anorexia nervosa young adults to have the same key staff and family-centred sessions over the 14-to-25 age span. Constrained by single-site study and small sample size, these preliminary data provide a rationale for wider implementation and controlled follow-up studies.