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Key summary points: Aim: We aimed to evaluate the feasibility and efficacy of a short training course on frailty destined for primary health care (PHC) professionals. Findings: PHC professionals applied frailty screening strategies more frequently 3 months following the workshop compared to baseline and reported improvements in a) their familiarization with the frailty syndrome, b) self-perception of knowledge and skills to detect and manage frailty, and c) the attitude that frailty is an inevitable consequence of aging. Time restrictions was reported to be the main barrier to the application of frailty screening and management strategies. Message: A short skill-oriented training course can significantly and sustainably improve PHC professionals' attitudes and practices regarding frailty. Background: There is an unmet need for training primary health care professionals on frailty, especially in countries where geriatrics is still emerging. Purpose: We aimed to evaluate the feasibility and efficacy of a training course for primary health care professionals on the detection, assessment, and management of frailty. Methods: A single-day training course, developed and facilitated by three physicians trained in geriatrics abroad, was organized by the Aristotle University of Thessaloniki Primary Hearth Care Research Network. Primary health care professionals' attitudes, knowledge, and everyday practices regarding frailty were assessed by self-administered anonymous questionnaires (using Likert-type scales) at three time-points (before, upon completion of the training course, and 3 months afterward). Results: Out of 31 participants (17 physicians, 12 nurses, 2 health visitors; 87.1% women; mean age 46.4 years), 31(100%) filled in the first, 30(97%) the second, and 25(81%) the third questionnaire. Improvements were reported in familiarization with the frailty syndrome (p = 0.041) and in self-perception of knowledge and skills to detect (p < 0.001) and manage (p < 0.001) frailty, that were also sustained 3 months afterward (p = 0.001 and p = 0.003 respectively). Improvement was also observed in the attitude that frailty is an inevitable consequence of aging (p = 0.007) and in the frequency of application of screening (but not management) strategies, 3 months following the workshop compared to baseline (p = 0.014). Participants reported less disagreement with the statement that systematic screening for frailty was unfeasible in their daily practice at 3 months compared to baseline (p = 0.006), mainly due to time restrictions. Conclusion: A short skill-oriented training course can significantly and sustainably improve primary health care professionals' attitudes and practices regarding frailty. [ABSTRACT FROM AUTHOR]

Abstract We describe an intein based method to site-specifically conjugate Quantum Dots (QDs) to target proteins in vivo. This approach allows the covalent conjugation of any nanostructure and/or nanodevice to any protein and thus the targeting of such material to any intracellular compartment or signalling complex within the cells of the developing embryo. We genetically fused a pleckstrin-homology (PH) domain with the N-terminus half of a split intein (IN). The C-terminus half (IC) of the intein was conjugated to QDs in vitro. IC-QD's and RNA encoding PH-IN were microinjected into Xenopus embryos. In vivo intein-splicing resulted in fully functional QD-PH conjugates that could be monitored in real time within live embryos. Use of Near Infra Red (NIR)-emitting QDs allowed monitoring of QD-conjugates within the embryo at depths where EGFP is undetectable demonstrating the advantages of QD's for this type of experiment. In conclusion, we have developed a novel in vivo methodology for the site-specific conjugation of QD's and other artificial structures to target proteins in different intracellular compartments and signaling complexes.

Figurative language, including metaphors and similes, is a crucial component of communication; yet, it presents significant challenges for individuals with autism spectrum disorder (ASD). A critical gap in existing research is the impact of bilingualism on the ability of children with ASD to understand and produce non-literal speech. This study addresses this gap by examining the comprehension and production of metaphors and similes in monolingual and bilingual Greek-speaking children with high-functioning ASD. To the best of our knowledge, this is the first study to investigate these abilities in bilingual children with ASD. Thirty-three monolingual and 18 bilingual children participated in tasks designed to assess comprehension, production, and error patterns for metaphors and similes. The study has also investigated the roles of non-verbal intelligence, language skills (expressive vocabulary), and executive functions (working memory) in the children's performance in the metaphor and simile tasks. Results showed that the two groups did not differ in metaphor comprehension; however, bilingual autistic children with higher non-verbal intelligence appeared to have superior performance in metaphor comprehension compared to their bilingual peers with lower non-verbal intelligence. The bilingual autistic children outperformed their monolingual peers in metaphor production, likely due to their higher non-verbal intelligence ability, despite the fact that the bilingual group had lower expressive vocabulary scores than the monolingual children. Simile comprehension, on the other hand, favored monolingual children, while no significant group differences were observed in simile production. Regarding errors, both groups exhibited similar error patterns, with literal interpretations being the dominant error type across both groups, suggesting that pragmatic language difficulty is a hallmark feature in ASD. The findings challenge the misconception that bilingualism hinders language development in children with ASD and highlight its potential to provide benefits in the realm of non-literal language processing., (© 2025 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

The conditional Gaussian nonlinear system (CGNS) is a broad class of nonlinear stochastic dynamical systems. Given the trajectories for a subset of state variables, the remaining follow a Gaussian distribution. Despite the conditionally linear structure, the CGNS exhibits strong nonlinearity, thus capturing many non-Gaussian characteristics observed in nature through its joint and marginal distributions. Desirably, it enjoys closed analytic formulae for the time evolution of its conditional Gaussian statistics, which facilitate the study of data assimilation and other related topics. In this paper, we develop a martingale-free approach to improve the understanding of CGNSs. This methodology provides a tractable approach to proving the time evolution of the conditional statistics by deriving results through time discretization schemes, with the continuous-time regime obtained via a formal limiting process as the discretization time-step vanishes. This discretized approach further allows for developing analytic formulae for optimal posterior sampling of unobserved state variables with correlated noise. These tools are particularly valuable for studying extreme events and intermittency and apply to high-dimensional systems. Moreover, the approach improves the understanding of different sampling methods in characterizing uncertainty. The effectiveness of the framework is demonstrated through a physics-constrained, triad-interaction climate model with cubic nonlinearity and state-dependent cross-interacting noise.

Research in the field of figurative language processing in Autism Spectrum Disorders (ASD) has demonstrated that autistic individuals experience systematic difficulties in the comprehension of different types of metaphors. However, there is scarce evidence regarding metaphor production skills in ASD. Importantly, the exact source of metaphor processing difficulties in ASD remains largely controversial. The debate has mainly focused on the mediating role of structural language skills (i.e., lexical knowledge) and cognitive abilities (i.e., Theory of Mind and executive functions) in ASD individuals' ability to comprehend and generate metaphors. The present study examines metaphor comprehension and production in 18 Greek-speaking verbally able children with ASD and 31 typically-developing (TD) controls. Participants completed two tasks, namely, a low-verbal multiple-choice sentence-picture matching task that tested their ability to comprehend conventional predicate metaphors, and a sentence continuation task that assessed their ability to generate metaphors. The study also included measures of fluid intelligence, expressive vocabulary, and working memory within the sample. The results show that the ASD group had significantly lower performance than the TD group in both metaphor comprehension and production. The findings also reveal that expressive vocabulary skills were a key factor in the metaphor comprehension and production performance of the children with ASD. Working memory capacity was also found to correlate significantly with metaphor comprehension performance in the ASD group. Conversely, no correlations were found in the TD group with neither of the above factors. Of note, children with ASD generated significantly more inappropriate responses and no-responses to the metaphor production task compared with the control group. The overall results reveal that children with ASD had difficulty with both comprehending and using metaphorical language. The findings also indicate that TD children may employ diverse cognitive strategies or rely on different underlying skills when processing metaphors compared with children with ASD., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The purpose of this study was to identify the saponin and phenolic components in root extracts of Saponaria officinalis , a widespread species, found in Cyprus. A total of six major saponins, including gypsogenin and gypsogenic acid derivatives, as well as saponariosides C, D, and E, were identified using UHPLC/Q-TOF-MS analysis, with gypsogenin derivatives being the most common saponins detected through quantitative analysis. A total of six phenolic compounds were also identified, including rutin, quercetin galactoside, syringic acid, apigenin, protocatechuic, and vanillic acid. In addition to their saponin and phenolic contents, the root extracts were prepared through different extraction methods, and their biological activity was assessed. All samples demonstrated antioxidant capacity, as well as antibacterial activity, against four bacterial strains ( Escherichia coli , Staphylococcus aureus , Enterococcus faecalis , and Salmonella enteritidis ), with the acetone extract presenting higher susceptibility. The evaluation of anticancer activity in A375 (human malignant melanoma), HeLa (human cervical epithelioid carcinoma), and HaCaT (healthy human keratinocytes) cell lines revealed that the acetone extract of S. officinalis extract demonstrated a significant inhibitory effect on the proliferation of A375 cells in a concentration-dependent manner. None of the extracts demonstrated anti-neurotoxic potential against Aβ 25-35 cytotoxic peptides. The results of this study support previous findings that reveal that the Saponaria species are an excellent natural source of biologically active compounds with antioxidant, antimicrobial, and anticancer properties.

Despite the consensus that early identification leads to better outcomes for individuals with autism spectrum disorder (ASD), recent research reveals that the average age of diagnosis in the Greek population is approximately six years. However, this age of diagnosis is delayed by an additional two years for families from lower-income or minority backgrounds. These disparities result in adverse impacts on intervention outcomes, which are further burdened by the often time-consuming and labor-intensive language assessments for children with ASD. There is a crucial need for tools that increase access to early assessment and diagnosis that will be rigorous and objective. The current study leverages the capabilities of artificial intelligence to develop a reliable and practical model for distinguishing children with ASD from typically-developing peers based on their narrative and vocabulary skills. We applied natural language processing-based extraction techniques to automatically acquire language features (narrative and vocabulary skills) from storytelling in 68 children with ASD and 52 typically-developing children, and then trained machine learning models on the children's combined narrative and expressive vocabulary data to generate behavioral targets that effectively differentiate ASD from typically-developing children. According to the findings, the model could distinguish ASD from typically-developing children, achieving an accuracy of 96%. Specifically, out of the models used, hist gradient boosting and XGBoost showed slightly superior performance compared to the decision trees and gradient boosting models, particularly regarding accuracy and F1 score. These results bode well for the deployment of machine learning technology for children with ASD, especially those with limited access to early identification services.

Introduction: Reading comprehension is one of the most important skills learned in school and it has an important contribution to the academic success of children with Autism Spectrum Disorder (ASD). Though previous studies have investigated reading comprehension difficulties in ASD and highlighted factors that contribute to these difficulties, this evidence has mainly stemmed from children with ASD and intact cognitive skills. Also, much emphasis has been placed on the relation between reading comprehension and word recognition skills, while the role of other skills, including fluency and morphosyntax, remains underexplored. This study addresses these gaps by investigating reading comprehension in two groups of school-aged children with ASD, one with intact and one with low cognitive abilities, also exploring the roles of word decoding, fluency and morphosyntax in each group's reading comprehension performance., Methods: The study recruited 16 children with ASD and low cognitive abilities, and 22 age-matched children with ASD and intact cognitive skills. The children were assessed on four reading subdomains, namely, decoding, fluency, morphosyntax, and reading comprehension., Results: The children with ASD and low cognitive abilities scored significantly lower than their peers with intact cognitive abilities in all reading subdomains, except for decoding, verb production and compound word formation. Regression analyses showed that reading comprehension in the group with ASD and intact cognitive abilities was independently driven by their decoding and fluency skills, and to a lesser extent, by morphosyntax. On the other hand, the children with ASD and low cognitive abilities mainly drew on their decoding, and to a lesser extent, their morphosyntactic skills to perform in reading comprehension., Discussion: The results suggest that reading comprehension was more strongly affected in the children with ASD and low cognitive abilities as compared to those with intact cognitive skills. About half of the children with ASD and intact cognitive skills also exhibited mild-to-moderate reading comprehension difficulties, further implying that ASD may influence reading comprehension regardless of cognitive functioning. Finally, strengths in decoding seemed to predominantly drive cognitively-impaired children's reading performance, while the group with ASD and intact cognitive skills mainly recruited fluency and metalinguistic lexical skills to cope with reading comprehension demands, further suggesting that metalinguistic awareness may be a viable way to enhance reading comprehension in ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IT declared a shared affiliation with the author EP to the handling editor at the time of review., (Copyright © 2024 Peristeri, Frantzidis and Andreou.)

Impairments in the broader domain of pragmatics are considered to be a defining feature of Autism Spectrum Disorders (ASD). A challenging aspect of pragmatic competence is the ability to process nonliteral language. Interestingly, previous studies in figurative language comprehension in ASD have demonstrated conflicting results regarding participants' performance. The main scientific debate focuses on the underlying skills which facilitate processing of nonliteral speech in ASD. Namely, Theory of Mind (ToM), language abilities and Executive functions (EFs) are regarded as factors affecting autistic individuals' performance. This review addresses figurative language comprehension in ASD in light of the above three interpretive accounts. We reviewed data from recent studies in this field concluding that autistic children indeed encounter systematic difficulties in the processing of non-literal language. Moreover, only ToM and verbal skills were found to correlate the most with figurative language comprehension in ASD. Notably, we found that differences related to research methodology and tasks' properties may have led to discrepancies between studies' results. Finally, we argue that future studies should encompass in their experimental design figurative comprehension tasks with minimal linguistic demands and also measures of ToM, verbal ability and EFs in order to shed more light in the independent contribution of those skills to the processing of nonliteral language in ASD., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Intelligence profiles in autism have been characterized by great variability. The questions of how autistic children's intelligence changes over time, and what factors influence these changes deserve study as part of efforts to document child autism profiles, but also because the relationship between intellectual functioning and children's background characteristics is poorly understood, particularly in a longitudinal context. A total of 39 autistic children and 39 age-matched neurotypical children (5-9 years old) completed two IQ assessments at preschool age and up to 4 years later. Repeated-measures analyses assessed longitudinal changes in the children's verbal (VIQ), performance (PIQ), and full-scale IQ (FSIQ) at group level. We further sought to identify clusters with distinct profiles in each group by adopting an unsupervised K-means clustering approach, and detect possible between-subgroup differences in terms of children's socioeconomic status and autism severity. The largest cluster in the autistic group was composed of children whose PIQ significantly dropped at follow-up, while the second largest cluster improved in all quotients; the smallest cluster, wherein children had more highly educated mothers than the rest of the clusters, was characterized by large improvement in VIQ. For the neurotypical children, there was a two-cluster division; the majority of them improved in the three quotients, while very few dropped in PIQ at follow-up. The relation between socioeconomic status and IQ changes was significant for both groups. The findings demonstrate both the complexity of intelligence changes in autism and the need to view this complexity through the lens of the children's socioeconomic diversity., (© 2024 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Objective: To analyze the factors associated with overall survival (OS) and progression-free survival (PFS) in patients with ovarian cancer in Cyprus., Methods: We retrospectively analyzed data from patients with histologically confirmed epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC)., Results: A total of 106 women diagnosed with ovarian cancer were included, with a median age at diagnosis of 58 years. The Kaplan-Meier survival analysis showed a median OS of 41 months (95% C.I = 36.9, 45.1), and the FIGO stage ( p < 0.001), type of surgery ( p < 0.001) and performance status ( p < 0.001) were identified as statistically significant prognostic factors for OS. PFS analysis revealed the FIGO stage ( p = 0.006) and the performance status ( p < 0.001) as significant prognostic factors. Additionally, a Cox regression analysis for median OS was performed for patients with high-grade serous carcinoma, identifying the performance status, FIGO stage, and type of surgery as prognostic factors in univariate analysis. However, in the subsequent multivariate analysis, the performance status and the FIGO stage were confirmed to be the only statistically significant prognostic factors for OS ( p < 0.05)., Conclusions: This study confirms that the FIGO stage, performance status, and surgery type were considered as prognostic factors for OS in ovarian cancer.

Though previous studies with autistic individuals have provided behavioral evidence of animacy perception difficulties, the spatio-temporal dynamics of animacy processing in autism remain underexplored. This study investigated how animacy is neurally encoded in autistic adults, and whether potential deficits in animacy processing have cascading deleterious effects on their social functioning skills. We employed a picture naming paradigm that recorded accuracy and response latencies to animate and inanimate pictures in young autistic adults and age- and IQ-matched healthy individuals, while also employing high-density EEG analysis to map the spatio-temporal dynamics of animacy processing. Participants' social skills were also assessed through a social comprehension task. The autistic adults exhibited lower accuracy than controls on the animate pictures of the task and also exhibited altered brain responses, including larger and smaller N100 amplitudes than controls on inanimate and animate stimuli, respectively. At late stages of processing, there were shorter slow negative wave latencies for the autistic group as compared to controls for the animate trials only. The autistic individuals' altered brain responses negatively correlated with their social difficulties. The results suggest deficits in brain responses to animacy in the autistic group, which were related to the individuals' social functioning skills.

We examined the cognitive flexibility performance of young autistic children and a group of neurotypical peers. Thirty-six autistic children (72-83 months) and 200 age-matched typically-developing children were assessed on the Children's Color Trails Test (CCTT), a semantic and a phonemic verbal fluency task. The results showed that the autistic children performed worse than their neurotypical peers in the switching component of the CCTT. In the fluency tests, the autistic group generated overall fewer word items than their neurotypical peers, however, their poorer performance was driven by specific linguistic stimuli in the fluency tasks. The findings suggest that cognitive flexibility for the autistic children was affected in the nonverbal CCTT only, while poor performance in semantic and phonemic fluency seemed to be inherent to the language properties of the verbal fluency tasks., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is compromised, including cancer. The aim of this study was to explore the prognostic and/or diagnostic potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) in human tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with tumor development, histopathological parameters, distribution of tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human malignancies investigated, IL-37 exhibits higher expression levels in tumors of lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and tumor stage, whereas their high mRNA levels are favorable prognostic factors for the overall survival of patients. What is more, IL-37 correlates positively with a LUAD-associated transcriptomic signature, and its nucleotide changes and expression levels are linked with distinct infiltration patterns of certain cell subsets known to control LUAD anti-tumor immune responses. Our data indicate the potential value of IL-37 and its receptor SIGIRR to serve as biomarkers and/or immune-checkpoint therapeutic targets for LUAD patients. Further, the data highlight the urgent need for further exploration of this cytokine and the underlying pathogenetic mechanisms to fully elucidate its implication in LUAD development and progression.