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This study explored the affective outcomes students perceived from participating in a summer program and the program components that contributed to participants' perceived affective development. Participants were 55 middle school students (29 girls) with intellectual gifts who participated in a 4-day-long residential program conducted in a western state in India. Participants wrote descriptive reflections responding to a 16-item open-ended survey. Matrix coding was used to code affective outcomes and the associated program components. Thematic analyses of responses revealed five themes that depicted improvement in participants' (a) confidence and courage, (b) self-awareness, (c) social awareness, (d) social skills, and (e) inspiration. Leadership workshops and group activities, rural experience, and camp structure were discussed most frequently in relation to specific affective outcomes. Findings indicated that a direct and well-planned affective intervention can provide opportunities for social and emotional learning. Implications for holistic talent development programming have been discussed.

The present study investigates the impact of meaningful input on L2 learners' vocabulary use and their fluency in oral performance (immediate and repeat tasks), as well as whether the effects are mediated by learners' prior vocabulary knowledge and working memory. Ninety university students learning English as a foreign language were randomly assigned to one of three groups: input (N = 29), input repetition (N = 32), and no-input (i.e., baseline group) (N = 29). The input group watched L2 videos prior to performing an immediate oral task, whereas the input repetition group watched the same videos not only before but also after the immediate oral task. The no-input group only performed the oral tasks without watching the videos. The three groups repeated the same oral task after two days. Results did not show a significant effect of task repetition, input, and input repetition on learners' lexical use and fluency. However, the fluency and lexical complexity in learners' L2 speech can be predicted by their receptive vocabulary knowledge and working memory capacity to some extent.

This study explored the affective outcomes students perceived from participating in a summer program and the program components that contributed to participants’ perceived affective development. Participants were 55 middle school students (29 girls) with intellectual gifts who participated in a 4-day-long residential program conducted in a western state in India. Participants wrote descriptive reflections responding to a 16-item open-ended survey. Matrix coding was used to code affective outcomes and the associated program components. Thematic analyses of responses revealed five themes that depicted improvement in participants’ (a) confidence and courage, (b) self-awareness, (c) social awareness, (d) social skills, and (e) inspiration. Leadership workshops and group activities, rural experience, and camp structure were discussed most frequently in relation to specific affective outcomes. Findings indicated that a direct and well-planned affective intervention can provide opportunities for social and emotional learning. Implications for holistic talent development programming have been discussed.

Abstract Aims Decision‐makers still predominantly focus on the perspective of non‐patient stakeholders, which may deviate from the unique perspective of heart failure (HF) patients. To enhance patient‐centred decision‐making, there is a need for more patient‐based evidence derived directly from the patients themselves. Hence, this study aimed to understand (i) HF patients' unmet medical needs and preferred treatment outcomes; (ii) patients' risk tolerance; and (iii) their information needs, uncertainties and satisfaction towards HF treatment. Methods This qualitative patient preference study consisted of a literature review with a systematic search strategy and semi‐structured interviews with HF patients, analysed using the framework method. During the interviews, patients were asked to rank a predefined list of disease and treatment‐related characteristics informed by the literature review and were able to spontaneously raise additional characteristics. Results The study included 14 Belgian HF patients (age range: 58–79, mean age: 72). (i) Regarding their unmet medical needs, HF patients reported that the most important unmet medical needs were shortness of breath and fatigue, as they negatively impact their quality of life (QoL) and independence. In the ranking exercise, patients prioritized improvements in QoL over improvements in life expectancy, whereby the following characteristics received the highest cumulative score: (1) independence, (2) shortness of breath, (3) impaired renal function, (4) survival, (5) fatigue, (6) risk of hospitalization and (7) communication with and between physicians. Patients most often spontaneously raise characteristics related to the general care process. Mechanism of action, route of administration, dose frequency and weight fluctuations scored among the least important characteristics. (ii) Regarding patients' risk tolerance towards HF treatment, some of the patients expressed zero tolerance for side effects, as they had not yet experienced any discomfort caused by the treatment or disease. (iii) Regarding their information needs, patients voiced their desire to receive practical and comprehensible advice orally from their physician because they highly value individualized treatment decision‐making. Patients also expressed uncertainties regarding whether the experienced effects were due to their treatment, disease, ageing or other comorbidities. Conclusions This study shows that, besides increasing life expectancy, HF patients prioritize improvements in symptoms and side effects reducing their QoL and independence, such as shortness of breath and fatigue. The patient‐relevant characteristics identified in this study, from the perspective of HF patients themselves, may be useful to inform clinical trial endpoint selection and guide downstream drug development, evaluation and clinical decision‐making towards addressing the unmet medical needs and treatment outcomes of importance to HF patients.

Researchers have argued that many leaders, such as CEOs and politicians, tend to possess narcissistic traits. At healthy and productive levels, narcissistic traits, such as self-promotion, may actually be an advantage to achieving success in some fields. Yet, few researchers have explored gifted narcissists as a twice-exceptionality. This article discusses the gifted narcissist profile and grandiose narcissism in particular. Following a brief introduction to key terms, the gifted narcissist profile is explored through the augmented theory of successful intelligence. The impact of giftedness on individuals with a narcissistic personality disorder is discussed in terms of positive and negative effects. Presidents, autocratic leaders, and cult leaders are presented as examples of gifted grandiose narcissists.

Developmental Coordination Disorder (DCD), also known as Dyspraxia, is an often overlooked or misdiagnosed disorder and little research exists on how it manifests among cognitively gifted children. The purpose of this study was to examine clinical profiles among 25 children diagnosed with DCD and identified as cognitively gifted to explore the twice exceptional profile of DCD among gifted children. We explore how DCD manifests among children with cognitive gifts, considerations for identification, and gifted education services.

Abstract Inborn errors of tyrosine metabolism result in patient’s inability to degrade tyrosine. Current treatment consists of a phenylalanine and tyrosine restricted diet and nitisinone, causing a block in the tyrosine degradation pathway. However, tyrosine levels will increase, leading to acquired hypertyrosinemia, implying the need for an add-on treatment. Tyrosine ammonia lyases (TAL) can provide such an add-on treatment as they catalyze the deamination of tyrosine into p-coumaric acid and ammonia. In this study, we developed a robust high-throughput screening (HTS) assay to assess the capacity of bacterial TAL enzymes to decrease excessive tyrosine. The assay is based on the spectrophotometric quantification of p-coumaric acid after conversion of tyrosine by bacterial TAL. As a benchmark, TAL from Flavobacterium johnsoniae (FjTAL) was used to optimize the assay. Optimal growth conditions for high-level protein expression were determined by incubating transformed Escherichia coli BL21 (DE3) cells at different temperatures during various incubation times. Subsequently, assay temperature and pH were optimized followed by testing different ratios of tyrosine assay mixes to bacterial lysate. Finally, assay robustness and functionality were evaluated. Optimal FjTAL expression was obtained after incubation for 24 h at 22 °C. Ideal assay conditions consist of a 80/20 ratio of 1 mM tyrosine assay mix to FjTAL lysate performed at pH 9.2 and 37 °C. The robustness test showed Z′ values > 0.4 and signal window values > 2 without edge or drift effects. As proof-of-principle, we successfully determined the catalytic activity of two other bacterial TAL enzymes RsTAL (5.718.10–3 ± 0.21.10–3) and SeSAM8 (4.658.10–3 ± 0.37.10–3). A robust, simple and reliable HTS assay was thus developed to evaluate the tyrosine degradation capacity of bacterial TAL enzymes.

Abstract Background Most studies on tumour progression from precursor lesion toward gallbladder adenocarcinoma investigate lesions sampled from distinct patients, providing an overarching view of pathogenic cascades. Whether this reflects the tumourigenic process in individual patients remains insufficiently explored. Genomic and epigenomic studies suggest that a subset of gallbladder cancers originate from biliary intraepithelial neoplasia (BilIN) precursor lesions, whereas others form independently from BilINs. Spatial transcriptomic data supporting these conclusions are missing. Moreover, multiple areas with precursor or adenocarcinoma lesions can be detected within the same pathological sample. Yet, knowledge about intra-patient variability of such lesions is lacking. Methods To characterise the spatial transcriptomics of gallbladder cancer tumourigenesis in individual patients, we selected two patients with distinct cancer aetiology and whose samples simultaneously displayed multiple areas of normal epithelium, BilINs and adenocarcinoma. Using GeoMx digital spatial profiling, we characterised the whole transcriptome of a high number of regions of interest (ROIs) per sample in the two patients (24 and 32 ROIs respectively), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Human gallbladder organoids and cell line-derived tumours were used to investigate the tumour-promoting role of genes. Results Spatial transcriptomics revealed that each type of lesion displayed limited intra-patient transcriptomic variability. Our data further suggest that adenocarcinoma derived from high-grade BilIN in one patient and from low-grade BilIN in the other patient, with co-existing high-grade BilIN evolving via a distinct process in the latter case. The two patients displayed distinct sequences of signalling pathway activation during tumour progression, but Semaphorin 4 A (SEMA4A) expression was repressed in both patients. Using human gallbladder-derived organoids and cell line-derived tumours, we provide evidence that repression of SEMA4A promotes pseudostratification of the epithelium and enhances cell migration and survival. Conclusion Gallbladder adenocarcinoma can develop according to patient-specific processes, and limited intra-patient variability of precursor and cancer lesions was noticed. Our data suggest that repression of SEMA4A can promote tumour progression. They also highlight the need to gain gene expression data in addition to histological information to avoid understimating the risk of low-grade preneoplastic lesions.

The purpose of the present study was to evaluate a cybersecurity and digital forensics enrichment program for gifted and talented students to determine students' perceptions of this enrichment course. We evaluated data from 25 secondary education students and one educator to examine their perceptions of the program. Responses from students and the teacher indicated that the cyber enrichment program was well-received by students. Findings demonstrated that authentic and hands-on experiences with cybersecurity and digital forensics were associated with students' perceiving the program as appealing and meaningful and perceiving themselves as highly efficacious when it comes to cybersecurity and digital forensics. Future research directions are discussed.

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[18F]-fluoro-d-glucose ([18F]FDG), the most common tracer used in clinical imaging, to form [18F]-labeled disaccharides for detecting microorganisms in vivo based on their bacteria-specific glycan incorporation. When [18F]FDG was reacted with β-d-glucose-1-phosphate in the presence of maltose phosphorylase, the α-1,4- and α-1,3-linked products 2-deoxy-[18F]-fluoro-maltose ([18F]FDM) and 2-deoxy-2-[18F]-fluoro-sakebiose ([18F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[18F]fluoro-trehalose ([18F]FDT), 2-deoxy-2-[18F]fluoro-laminaribiose ([18F]FDL), and 2-deoxy-2-[18F]fluoro-cellobiose ([18F]FDC). We subsequently tested [18F]FDM and [18F]FSK in vitro, showing accumulation by several clinically relevant pathogens including Staphylococcus aureus and Acinetobacter baumannii, and demonstrated their specific uptake in vivo. Both [18F]FDM and [18F]FSK were stable in human serum with high accumulation in preclinical infection models. The synthetic ease and high sensitivity of [18F]FDM and [18F]FSK to S. aureus including methicillin-resistant (MRSA) strains strongly justify clinical translation of these tracers to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [18F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications.

Positive creativity involves creative ideas and products that are beneficial to humanity. This paper discusses the importance of fostering positive and transformational creativity in PK-12 and college settings, and concrete classroom strategies for nurturing positive creativity through a service learning pedagogy. A brief history of service learning pedagogy is discussed, along with a practical application of the K-12 Developmental Service Learning Typology, a theoretical service learning pedagogical model. This practical application highlights three examples of how service learning can foster positive and transformational creativity: experiential learning through community service or volunteering, problem-based learning through community exploration, and using Destination Imagination as a form of social or community activism. The latter two examples demonstrate using curiosity to create positive, novel, and useful products through a cycle of deep exploration of topics that each student has an intense interest in, called the Roberts Curiosity Community Exploration Cycle (R-CCEC).

We review the musical conservatory as a model for educators to learn how to enhance admissions, instruction, and assessment in liberal arts collegiate settings. Although conservatories serve primarily students wishing to enter musical careers of various kinds, the model on which they are based can, in many ways, serve any student and any school. We review some of the history of conservatories and describe how they work. Next, we explore how they develop a wide range of technical, cognitive, affective, and conative skills. Finally, we show how the skills they develop are important not just for music students but also for all students who will enter the world of work and face difficult and unexpected adaptive challenges.

Summary: The development of fast ligation chemistries for the site-specific modification of proteins has become a major focus in chemical biology. We describe steps for preparing an oxalyl thioester precursor in the form of an N-oxalyl perhydro-1,2,5-dithiazepine handle, i.e., the oxoSEA group, and incorporating it into a peptide modifier using solid phase peptide synthesis. We then detail procedures for its application for the modification of an N-terminal Cys-containing B1 domain of the streptococcal G protein using the native chemical ligation.For complete details on the use and execution of this protocol, please refer to Snella et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

AbstractIntroduction: Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients.Aims: The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage.Materials and methods: One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose.Results: Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl.Conclusions: One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects.