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Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies. Among them, antibody-based therapies have been the most studied. Immunoconjugates consist of a carrier portion, frequently represented by an antibody, linked to a toxic moiety, i.e., a drug, toxin, or radionuclide. While the efficacy of immunoconjugates is well demonstrated in the therapy of hematological tumors and more recently also of epithelial ones, their potential as therapeutic agents against sarcomas is still not completely explored. In this paper, we summarize the results obtained with immunoconjugates targeting sarcoma surface antigens, considering both preclinical and clinical studies. To date, the encouraging results obtained in preclinical studies allowed nine immunoconjugates to enter clinical trials, demonstrating the validity of immunotherapy as a promising pharmacological tool also for sarcoma therapy. [ABSTRACT FROM AUTHOR]

• Norwegian, Swedish, and Danish participants differ in their motivations to learn Arabic. • Reactance is most pronounced among the Norwegian participants. • International posture is associated with the participants' motivation to learn Arabic. • Gender differences were found with respect to the participants' use of metacognitive strategies. • The participants do not appear to have distinct motivational selves as theorized by the L2MSS. Rising levels of immigration, especially from the Middle East and North Africa, have led to significant socio-demographic changes and increasing levels of linguistic diversity in Scandinavian countries. In parallel with these developments, a growing number of students in Norway, Sweden, and Denmark have started to learn Arabic at school and university. Learning Arabic presents both challenges and opportunities. For example, it furthers the goal of states to develop multilingual citizens, yet it also tasks educational institutions with designing Arabic courses that reflect the interests and aspirations of their students and provide them with the tools to make sustained progress. In order to accomplish this, it is important to first understand what motivates students to learn Arabic and the extent to which they use self-regulatory strategies to enhance their learning. This article reports on a study that explored the self-regulation and language learning motivation of university students (N = 96) learning Arabic in Norway, Sweden, and Denmark. The findings revealed that the Norwegian, Swedish, and Danish participants differed statistically significantly in their motivation to learn Arabic. Statistically significant gender differences were also found with respect to the participants' self-regulation. The study provides important insights into student metacognition, autonomy, and motivation to learn non-European languages in the Scandinavian context. [ABSTRACT FROM AUTHOR]

• A growing number of studies are exploring NNSTs' multilinguality. • NNSTs can develop a reactive multilingual identity due to native-speakerism. • NNSTs in Europe support multilingualism but do not always understand it. • Monolingual ideologies are especially prevalent in Asia and the UK. With many countries now implementing multilingual educational initiatives in schools, there is a need to reconfigure training programs and encourage teachers to develop a multilingual identity so that they can better promote multilingualism among their students. At present, monolingual ideologies dominate the language education landscape, particularly disadvantaging non-native speaker teachers (NNSTs), who are proficient multilinguals by default and who might best embody the successful language learner model for emergent multilinguals. Studies on NNSTs, however, have traditionally focused on their status as deficient native speakers instead of exploring their multilinguality, although this has started to change in recent years. This study represents a critical review of empirical studies (n = 84) from 2009–2018 that reflect this change. The review indicates that a growing number of studies have started to document NNSTs' unique affordances and multilingual practices in the classroom globally, that NNSTs can develop a reactive multilingual identity in response to native-speakerism, and that learners, when engaged by researchers, do recognize the multilingual affordances of NNSTs. The study's findings should contribute to the growing body of research on multilingual teacher identity, affordances, and practices, especially as this concerns NNSTs. [ABSTRACT FROM AUTHOR]

Background: The rapid evolution of the epidemiological picture and the recent SARS-COV-2 pandemic has expressed the vulnerabilities of health systems and focuses attention on the population's needs. The nurse's figure in the care teams is universally identified; however, the implementation of the role within some care settings turns out to be complex and challenging. This integrative review aims to identify the barriers and facilitators in implementing the role of the nurse in primary care settings. Methods: An integrative review was conducted on the Medline and Cinahl databases until 9 June 2020. Qualitative, quantitative, and Mixed-method research studies were selected to identify studies related to the barriers and facilitators of the nurse's role in nursing facilities' primary care. For the extraction of the results, the Consolidating Framework for Research Implementation (CFIR) was used to identify the factors that influence implementation in health care. Results: Following the duplicates' removal, the search identified 18,257 articles, of which 56 were relevant to the inclusion criteria; therefore, they were included in the summary. The selected studies were conducted in thirteen countries, most from Oceania, Europe, North America, Latin America, and the Caribbean. The barriers reported most frequently concern the nursing profession's regulatory and regulatory aspects within the contexts of care, cultural and organizational aspects, training, and the transfer of specific skills, which were previously designated to doctors. The facilitators are mainly linked to the nurse's adaptability to the various contexts of care, recognizing the patient's role, and the desire to develop multidisciplinary and effective working groups to respond to the health needs of the population in primary care contexts. Conclusion: This review highlighted the main barriers and facilitators in implementing the nurse's role in primary care settings. These results offer useful elements for stakeholders to identify effective strategies in preparing programs and activities for implementing the nurse's role, acting on the elements identified as barriers and favouring the aspects that emerge as facilitators. [ABSTRACT FROM AUTHOR]

Background: Wnt/β-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis. Methods: Proteins and target genes of both pathways were analysed by RT-qPCR and IHC in tissues from healthy faecal immunochemical test positive (FIT+, n = 17), FAP (n = 17) and CRC (n = 15) subjects. CRC-related mutations were analysed through NGS and Sanger. Oral, faecal and mucosal microbiota was profiled by 16 S rRNA-sequencing. Results: We found simultaneous hyperactivation of Wnt/β-catenin and PI3K/mTOR pathways in FAP-lesions compared to CRCs. Wnt/β-catenin molecular markers positively correlated with Clostridium_sensu_stricto_1 and negatively with Bacteroides in FAP faecal microbiota. Alistipes, Lachnospiraceae, and Ruminococcaceae were enriched in FAP stools and adenomas, the latter also showing an overabundance of Lachnoclostridium, which positively correlated with cMYC. In impaired-mTOR-mutated CRC tissues, p-S6R correlated with Fusobacterium and Dialister, the latter also confirmed in the faecal-ecosystem. Conclusions: Our study reveals an interplay between Wnt/β-catenin and PI3K/mTOR, whose derangement correlates with specific microbiota signatures in FAP and CRC patients, and identifies new potential biomarkers and targets to improve CRC prevention, early adenoma detection and treatment. [ABSTRACT FROM AUTHOR]

Copper, though toxic in excess, is an essential trace element that serves as a cofactor in many critical biological processes such as respiration, iron transport, and oxidative stress protection. To maintain this balance between requirement and toxicity, biological systems have developed intricate systems allowing the preservation of homeostasis while ensuring delivery of copper to the appropriate cellular component. The nematode Caenorhabditis elegans was exploited to assess the effects of copper toxicity at the population level to identify key changes in life cycle traits including, lethality, brood size, generation time, growth, and life span. To enhance our understanding of the complexities of copper homeostasis at the genetic level, the expression profile and functional significance of a putative copper cytoplasmic metallochaperone cutc-1 were analyzed. Using quantitative PCR technology, cutc-1 was found to be downregulated with increasing CuSO4 concentrations. However, although total (whole body) copper levels increased in nematodes exposed to elevated levels of copper, wild-type and knock down of cutc-1 by RNA-mediated interference (RNAi) were statistically indistinguishable. Nevertheless, RNAi of cutc-1 affected brood size, growth and induced a marked increase in protruding vulva and bagging phenotypes at higher copper exposures. This indicates that cutc-1 plays a crucial role in the protection from excess copper. [ABSTRACT FROM AUTHOR]

Objective: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy‐related psychoses, and has unknown causation. Methods: We conducted a case–control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis; 49 had postictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated. Results: Cases were more likely to have seizure clustering (odds ratio [OR] = 7.59, p < 0.001), seizures with a recollected aura (OR = 2.49, p = 0.013), and a family history of psychiatric disease (OR = 5.17, p = 0.022). Cases showed predominance of right temporal epileptiform discharges (OR = 4.87, p = 0.007). There was no difference in epilepsy duration, neuroimaging findings, or antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R2 = 3%, p = 6 × 10−3), but not significantly different from 945 independent patients with schizophrenia (R2 = 0.1%, p = 0.775). Interpretation: Postictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (postictal psychosis) in a common disease. ANN NEUROL 2021;90:464–476 [ABSTRACT FROM AUTHOR]

Abstract: A series of 4 and 5 nitro-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1–8) was synthesized by reaction of benzenesulfonamide derivatives with 4 and 3-nitrophthalic anhydrides. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated hCA IX and XII. Most of the novel compounds were medium potency-weak hCA I inhibitors (K is in the range of 295–10,000nM), but were more effective hCA II inhibitors (K is of 1.7–887nM). The tumor-associated hCA IX was also inhibited, with K is in the micromolar range, whereas against hCA XII the inhibition constants were in the range of 90–3746nM. The structure–activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking studies was performed in order to rationalize the activities reported and binding mode to different hCA as inhibitors. [Copyright &y& Elsevier]