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The introduction of generative artificial intelligence (AI) to the wider public could have a huge impact on EFL learning and teaching. Researchers have voiced concerns that learners might lean too much on technology. Previous studies have investigated the use of AI tools in L2 writing with various populations and found that it was difficult for teachers to detect use of AI and that teachers mainly relied on linguistic strategies to detect AI-generated texts. This paper reports on a qualitative study that investigated whether novice English teachers were able to detect AI-generated writing and which strategies they used to do this. The results show that some novice teachers are quite good at detecting AI-generated texts, while others proved to have more difficulties. The teachers used both linguistic and content-related strategies to detect AI-generated writing. The results point towards the value of including this topic in teaching methodology courses in (initial) teacher training programmes.

In this article we describe our five-year research project on the notorious radical free speech service and fringe platform Gab. During these years we scraped an entire platform, prepared it into a dataset for analysis, and opened it up to a broader community of students and researchers. Each of these projects provides us not just with a small slice of platformized far-right culture but also with a larger sphere of a fringe platform. However, the overarching goal of the Gab project was to contribute to a methodology for the study of the contemporary platformized far right. The atypical nature of the project posed many methodological, epistemological, and legal challenges. It therefore kicked off an institutional learning process about the possibilities, legal boundaries, and best practices for research compliant with General Data Protection Regulation (GDPR). In this article we argue that the study of the platformized far right should have a thorough understanding of the medium on which the object is present, as well as the methods with which the object is captured. What is more, scholars that use digital tools and data methods for capture and analysis of web platforms must become literate in operating them. Consequently, data-driven research on the far right is naturally interdisciplinary and therefore cooperative and adherent to the principles of open science.

This case study presents an institutional approach to curriculum enhancement and co-creation. It explores how these two elements of a university's strategy interlink through institutional values, curriculum development initiatives, and the advent of a new recognition scheme for student co-creators at Queen Mary University of London in the UK. It explores how the delivery of curriculum enhancement projects has been made possible through co-creation with students and discusses its outcomes: curriculum enhancement resources for staff and students, recognition for students, and joint presentations and publications. This case study also reflects on the experience of student co-creators and the benefits and challenges for staff and the institution, considers the specific contexts required to promote a shift in institutional culture towards co-creation, and shares successes and recommendations for implementing this approach.

Abstract Background Recovery from severe mental illness, including psychosis has been described as a personal and unique process, but it rarely is a journey undertaken without profound influences of significant others (family, mental health professionals). Diverging perspectives between persons with severe mental illness, family and professionals are frequent during the recovery process, notably in psychotic disorders. We aimed to explore processes of collaboration during recovery, to inform recovery supporting practices. Methods Current qualitative study had a participatory design and was set within long-term mental healthcare for severe mental illness. We conducted semi-structured interviews and focus groups with persons with severe mental illness (most had a history of psychosis), family and professionals on their mutual contact during recovery. Using reflexive thematic analysis, we developed themes representing processes of collaboration during recovery. Results We described roles persons with severe mental illness, family and professionals attribute to each other in mutually influential terms of unconditional and meaningful contact (which takes time to establish) and problem-oriented aspects. Secondly, experienced differences over problem definition, “needing help” and consequently over the role parties attribute to one another, may result in negative interactions, in the area of having expectations; (not) informing; (not) having agency to change; experiencing (dis)agreement or struggle. Conclusions unconditional, meaningful contact and knowing each other’s perspective are important to fruitful interaction in a triad when perspectives on mental health problems diverge. Relationally centered and process oriented care with continuity of family and professionals involved are needed to advance recovery in severe mental illness, especially psychosis.

Objective: The main purpose of this study is to evaluate 1) the three-dimensional (3D) glenohumeral relationship in cuff tear arthropathy (CTA) and 2) the correlation between different types of rotator cuff tears (RCTs) and the 3D glenohumeral relationship. Method: A total of 124 patients with CTA and 60 control patients were included in this study. 3D models of computed tomography images of the shoulder were reconstructed to evaluate the position of the humerus in relation to the scapula using a Cartesian coordinate system. The glenohumeral relationship of the CTA group is compared to the control group (group N). Next, the CTA group is divided into three subgroups depending on the (im)balance of the transverse force couple (TFC): a balanced RCT group (group B, n = 50), a group with an imbalance of the TFC to anterior (group A, n = 30), and a group with an imbalance of the TFC to posterior (group P, n = 44). The glenohumeral relationship of the RCT group is compared to a control group of 60 patients without RCT (group N). Results: The CTA group (96° ± 1°) was significant (P

Introduction: Small-molecule HIF stabilizers are being misused in sports to ‘artificially’ increase red blood cells. WADA banned their use, but the structural variety in this relatively new class of performance enhancing drugs and the rapid pace at which new drug candidates are emerging hampers their detection in biological fluids, as many currently used techniques target specific structures – a problem also encountered with NPS. Therefore, a future-proof strategy was envisaged, capable of detecting ANY HIF stabilizer (known AND unknown ones). Methods: A previously developed cell-based assay, monitoring the upstream mechanism of HIF1 activation (heterodimerization of HIF1α with HIF1β), was used to detect HIF stabilizers in spiked urine samples based on their HIF stabilizing activity. Results: The HIF1 bioassay proved to be universal, detecting every HIF stabilizer tested so far (including enarodustat, IOX2, JNJ-42041935, etc.). Using roxadustat as a prototype compound, sensitivity in known urine matrices was determined and ranged from 1-25 ng/mL. A limit-of-detection in blind-coded roxadustat-spiked urine matrices was determined to evaluate routine applicability of this activity-based detection method. Conclusions: Proof of concept was established that HIF stabilizers can be detected in spiked urine samples by a cell-based assay format through the measurement of increased HIF activation.

Purpose/Objective(s): To evaluate if stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has a durable effect on tumor control and can be delivered safely. Materials/Methods: Patients included in this retrospective study have been treated at our institution from January 2008 to December 2022. Eligibility criteria were diagnosis of HCC, BCLC stage 0-A-B, non-cirrhotic liver or liver with cirrhosis Child-Pugh class A, and a maximum of three lesions with a cumulative diameter of ≤ 6 cm. Patients with relapses after surgery, thermal ablation or TACE or patients awaiting transplant were also candidates for SBRT. SBRT was delivered in 6 fractions of 8 or 9 Gy. The primary endpoint was local (target) control (LC). Secondary endpoints were time to progression (TTP), overall survival (OS), response rate (RR) and toxicity. Results: A total of 52 patients received SBRT at our institution and 51 were included in this study. One patient objected and was excluded. Median follow-up was 2.1 years for LC and 2.3 years for OS. Median tumor size was 26 mm. LC rates at 1, 2, and 5 years were 100 %, 95 % and 95 % respectively. Median TTP was 45.6 months. Median OS was 7.1 years. RR was 96 %. No patients in this study have experienced SBRT related CTC AE grade ≥ 3 toxicity. Conclusion: SBRT resulted in excellent long-term local control rates and absence of severe toxicity in a group of HCC patients. The reported outcomes compare favorably with other local therapies. SBRT should be considered as one of the available local treatment options for HCC.

Abstract Background Psoroptic mange, caused by Psoroptes ovis mites, is affecting Belgian Blue cattle’s welfare and production potential. The Belgian Blue cattle—known for its high degree of muscling, low feed conversion ratio and high beef quality—is highly susceptible for this disease. Results In this study, we phenotyped 1975 Belgian Blue cattle from more than 100 different groups on commercial beef farms for their psoroptic mange susceptibility. Substantial individual differences were observed within these management groups, with lesion extent differences up to ± 15%. Animal models showed that estimated heritabilities were low for lesion extent and severe lesion extent (0.07 and 0.09, respectively) and 0.12 for the number of mites. A genome wide association study for mange susceptibility revealed signals on BTA6, BTA11, BTA15 and BTA24. In these regions, candidate genes GBA3, RAG2, and TRAF6 were identified. Conclusions Despite the challenges in phenotyping for psoroptic mange due to the timing of screening, the continuous evolution of lesions and different management conditions, we successfully conducted a study on the genetic susceptibility to psoroptic mange in Belgian Blue cattle. Our results clearly indicate that psoroptic mange is under polygenic control and the underlying candidate genes should be studied more thoroughly. This is the first study providing candidate genes for this complex disease. These results are already valuable for Belgian Blue breeding, however, further research is needed to unravel the architecture of this disease and to identify causal mutations.

Abstract Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

The linear and nonlinear optical properties of metallic nanoparticles have attracted considerable experimental and theoretical research interest. To date, most researchers have focused primarily on exploiting their plasmon excitation enhanced near-field and far-field responses and related applications in sensing, imaging, energy harvesting, conversion, and storage. Among numerous plasmonic structures, nanoparticle dimers, being a structurally simple and easy-to-prepare system, hold significant importance in the field of nanoplasmonics. In highly symmetric plasmonic nanostructures, although the odd-order optical nonlinearity of the near-surface region will be improved because of the enhanced near-fields, even-order nonlinear processes such as second-harmonic generation (SHG) will still be quenched and thus optically forbidden. Under this premise, it is imperative to introduce structural symmetry breaking to realize plasmon-enhanced even-order optical nonlinearity. Here, we fabricate a series of nanoparticle dimers each composed of two gold nanospheres with different diameters and subsequently investigate their structural asymmetry dependent linear and nonlinear optical properties. We find that the SHG intensities of gold nanosphere dimers are significantly enhanced by structural asymmetry under off-resonance excitation while the plasmonic near-field enhancement mainly affects SHG under on-resonance excitation. Our results reveal that symmetry breaking will play an indispensable role when designing novel coupled plasmonic nanostructures with enhanced nonlinear optical properties.

Abstract Background In patients without a family history, Duchenne muscular dystrophy (DMD) is typically diagnosed at around 4–5 years of age. It is important to diagnose DMD during infancy or toddler stage in order to have timely access to treatment, opportunities for reproductive options, prevention of potential fatal reactions to inhaled anesthetics, awareness of a child’s abilities needed for good parenting, and opportunities for enrolment in clinical trials. Method We aimed to develop a short risk assessment tool based on developmental milestones that may contribute to the early detection of boys with DMD in primary care. As part of the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with DMD), data on developmental milestones, symptoms and therapies for 76 boys with DMD and 12,414 boys from a control group were extracted from the health records of youth health care services and questionnaires. Multiple imputation, diagnostic validity and pooled backward logistic regression analyses with DMD (yes/no) as the dependent variable and attainment of 26 milestones until 36 months of age (yes/no) as the independent variable were performed. Descriptive statistics on symptoms and therapies were provided. Results A tool with seven milestones assessed at specific ages between 12 and 36 months resulted in a sensitivity of 79% (95CI:67–88%), a specificity of 95.8% (95%CI:95.3–96.2), and a positive predictive value of 1:268 boys. Boys with DMD often had symptoms (e.g. 43% had calf muscle pseudohypertrophy) and were referred to therapy (e.g. 59% for physical therapy) before diagnosis. Discussion This tool followed by the examination of other DMD-related symptoms could be used by youth health care professionals during day-to-day health assessments in the general population to flag children who require further action. Conclusions The majority of boys (79%) with DMD can be identified between 12 and 36 months of age with this tool. It increases the initial a priori risk of DMD from 1 in 5,000 to approximately 1 in 268 boys. We expect that other neuromuscular disorders and disabilities can also be found with this tool.

BackgroundAdverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.MethodsA multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.FindingsSubstantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.InterpretationOur findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.FundingNone.

This paper investigates an abortion clinic's procedural choices regarding the management of linguistic diversity. It focuses in particular on how language serves as capital for clients' agency in decision-making regarding their abortion treatment. Based on linguistic-ethnographic fieldwork in a Flemish abortion clinic, we analyse the clinic's institutional language policy, which states that clients should be able to speak Dutch, English or French in order to be eligible for a medical abortion--the alternative to a surgical abortion. We show how direct and smooth communication is considered a condition to ensure safety during the medical abortion treatment. We also discuss how, against the backdrop of the COVID-19 pandemic, the practical reorganisation of the clinic has led to more autonomy and empowerment for some clients, while it reinforced the already existing inequality for others. Finally, we discuss the clinic's struggles with and lack of reflection on language support services. We conclude that the case of the abortion clinic can be considered as one of exclusive inclusion, and suggest that a higher awareness of language support and a critical rethinking of the safety procedure could strengthen this clinic further in its endeavour to help women confronted with an unwanted pregnancy.

This longitudinal study explored the roles of item- and learner-related variables in L2 learners' development of productive collocation knowledge (L1 = Dutch; L2 = German; NLearners= 50). Learners' form recall knowledge of 35 target collocations was measured three times over a 3-year period. The item-related variables investigated were L1-L2 congruency, corpus frequency, association strength, and imageability. We also explored the learner-related variables L2 prior productive vocabulary knowledge and L2 immersion. Mixed-effects regression modeling indicated a significant effect of time, congruency, and prior productive vocabulary knowledge on learners' collocation learning. While learners' knowledge of congruent collocations remained relatively stable after year one, knowledge of incongruent collocations increased significantly. Learners' prior productive vocabulary knowledge was clearly associated with growth of productive collocation knowledge, but besides overall growth there were instances of attrition.

Summary: Neuroblastoma, a rare embryonic tumor arising from neural crest development, is responsible for 15% of pediatric cancer-related deaths. Recently, several single-cell transcriptome studies were performed on neuroblastoma patient samples to investigate the cell of origin and tumor heterogeneity. However, these individual studies involved a small number of tumors and cells, limiting the conclusions that could be drawn. To overcome this limitation, we integrated seven single-cell or single-nucleus datasets into a harmonized cell atlas covering 362,991 cells across 61 patients. We use this atlas to decipher the transcriptional landscape of neuroblastoma at single-cell resolution, revealing associations between transcriptomic profiles and clinical outcomes within the tumor compartment. In addition, we characterize the complex immune-cell landscape and uncover considerable heterogeneity among tumor-associated macrophages. Finally, we showcase the utility of our atlas as a resource by expanding it with additional data and using it as a reference for data-driven cell-type annotation.

Trust is argued to be essential in fostering cooperative communication, whereas a lack of trust is seen as detrimental to these aims. Over the years, there has been a slow but steady stream of research that has aimed to shed light on how trust is accomplished or broken down through discursive-interactional practices. In this mini review, we examine existing studies that take trust as a topic of investigation using micro-analytic, interactional methods, in order to provide readers with an up-to-date overview on new developments in this important field of research. From this review, we conclude that there exist two different, yet complementary, views on trust: Trust as an interactional principle and trust as a discursively accomplished phenomenon. We not only summarize important discursive work that provides a unique lens on how trust may be established and maintained through verbal and non-verbal resources, but also suggest some of the challenges interactional trust research still faces and some important areas for further investigation in which trust is a major concern.

Abstract Background Clinical trials in Alzheimer’s disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development. Methods We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01–01-2017 and 01–01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type. Results We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers. Conclusions As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets.

Key Clinical Message Belinostat therapy followed by hematopoietic stem cell transplantation is a promising salvage strategy for heavily pretreated patients with peripheral T‐cell lymphoma. Abstract Effective treatments for peripheral T‐cell lymphoma in the relapsed and refractory (r/r) setting are limited. However, with the development and approval of innovative therapies, effective therapeutic options are becoming available for this patient population. This case report describes the treatment course of a patient with multiple r/r nodal follicular T‐helper cell lymphoma of angioimmunoblastic type. Treatment with the histone deacetylase inhibitor belinostat as bridging, enabled allogeneic stem cell transplantation and resulted in a durable complete hematologic response for at least 21 months post‐transplantation.

IntroductionThe unique red blood cell (RBC) properties that characterize the rare neuroacanthocytosis syndromes (NAS) have prompted the exploration of osmotic gradient ektacytometry (Osmoscan) as a diagnostic tool for these disorders. In this exploratory study, we assessed if Osmoscans can discriminate NAS from other neurodegenerative diseases.MethodsA comprehensive assessment was conducted using Osmoscan on a diverse group of patients, including healthy controls (n = 9), neuroacanthocytosis syndrome patients (n = 6, 2 VPS13A and 4 XK disease), Parkinson’s disease patients (n = 6), Huntington’s disease patients (n = 5), and amyotrophic lateral sclerosis patients (n = 4). Concurrently, we collected and analyzed RBC indices and patients’ characteristics.ResultsStatistically significant changes were observed in NAS patients compared to healthy controls and other conditions, specifically in osmolality at minimal elongation index (Omin), maximal elongation index (EImax), the osmolality at half maximal elongation index in the hyperosmotic part of the curve (Ohyper), and the width of the curve close to the osmolality at maximal elongation index (Omax-width).DiscussionThis study represents an initial exploration of RBC properties from NAS patients using osmotic gradient ektacytometry. While specific parameters exhibited differences, only Ohyper and Omax-width yielded 100% specificity for other neurodegenerative diseases. Moreover, unique correlations between Osmoscan parameters and RBC indices in NAS versus controls were identified, such as osmolality at maximal elongation index (Omax) vs. mean cellular hemoglobin content (MCH) and minimal elongation index (EImin) vs. red blood cell distribution width (RDW). Given the limited sample size, further studies are essential to establish diagnostic guidelines based on these findings.

Discussions on citizenship always reflect broader political debates on the desired moral fabrics of a society. Evolving from a merely national subject, questions on children and young people's citizenship and citizenship education have over the past decades gained interest in European policy. Through a thematical-rhetorical analysis of European policy documents, this article engages in the European moral-political discussion on "good" citizenship and citizenship education for children and young people. The study shows that European conceptions of good citizenship and citizenship education fluctuate over time, responding to major societal crises. Focusing on the future of European society, European policy seems to project contemporary societal concerns onto children and young people's desired forms of citizenship, endorsing the idea of children as "citizens-in-the-making." Overall, European policy adopts a highly depoliticised perspective to citizenship that risks constricting, rather than enabling, the actual democratic citizenship of children and young people.

Abstract Objective This study determined patterns of knee osteoarthritis (OA) management by general practitioners (GPs) using routine healthcare data from Dutch general practices from 2011 to 2019. Design A retrospective cohort study was conducted using the Integrated Primary Care Information database between 2011 and 2019. Electronic health records (EHRs) of n = 750 randomly selected knee OA patients (with either codified or narrative diagnosis) were reviewed against eligibility criteria and n = 503 patients were included. Recorded information was extracted on GPs’ management from six months before to three years after diagnosis and patterns of management were analysed. Results An X-ray referral was the most widely recorded management modality (63.2%). The next most widely recorded management modalities were a referral to secondary care (56.1%) and medication prescription or advice (48.3%). Records of recommendation of/referral to other primary care practitioners (e.g. physiotherapists) were found in only one third of the patients. Advice to lose weight was least common (1.2%). Records of medication prescriptions or recommendation of/referral to other primary care practitioners were found more frequently in patients with an X-ray referral compared to patients without, while records of secondary care referrals were found less frequently. Records of an X-ray referral were often found in narratively diagnosed knee OA patients before GPs recorded a code for knee OA in their EHR. Conclusion These findings emphasize the importance of better implementing non-surgical management of knee OA in general practice and on initiatives for reducing the overuse of X-rays for diagnosing knee OA in general practice.