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Nesta discussão, defendemos um modelo (mais) amplo de estudos sobre o fandom transcultural que, ao mudar o foco para as afinidades afetivas que despertam o interesse dos fãs em objetos transculturais, pretende corrigir as análises centradas na nação de fandoms transfronteiriços. Nosso argumento é o de que a abordagem binária do fandom transnacional mantida por pesquisadores da globalização das mídias, como Koichi Iwabuchi, no contexto do Leste Asiático, pouco faz para o avanço de nossa compreensão sobre o motivo pelo qual os fãs se envolvem em fandoms transfronteiriços e as implicações das suas atividades sobre como entendemos o fluxo global de textos midiáticos. Neste ensaio, consideramos uma abordagem alternativa aos fandoms transculturais, a qual se preocupa menos com as nações do que com os fãs em si. Não procuramos redimir nem condenar os fãs, mas os situar nos seus diversos contextos – não apenas sociopolíticos e econômicos, mas também populares, culturais, sexuais, de gênero etc.

Abstract In situ electrochemistry on micron and submicron-sized individual particles and thin layers is a valuable, emerging tool for process understanding and optimization in a variety of scientific and technological fields such as material science, process technology, analytical chemistry, and environmental sciences. Electrochemical characterization and manipulation coupled with soft X-ray spectromicroscopy helps identify, quantify, and optimize processes in complex systems such as those with high heterogeneity in the spatial and/or temporal domain. Here we present a novel platform optimized for in situ electrochemistry with variable liquid electrolyte flow in soft X-ray scanning transmission X-ray microscopes (STXM). With four channels for fluid control and a modular design, it is suited for a wealth of experimental conditions. We demonstrate its capabilities by proving the reversible oxidation and reduction of individual microbial biofilm structures formed by microaerophilic Fe(II)-oxidizing bacteria, also known as twisted stalks. We show spectromicroscopically the heterogeneity of the redox activity on the submicron scale. Examples are also provided of electrochemical modification of liquid electrolyte species (Fe(II) and Fe(III) cyanides), and in situ studies of electrodeposited copper nanoparticles as CO2 reduction electrocatalysts under reaction conditions.

Purpose: Limited research exists assessing speech perception in school-age children with speech sound disorder (SSD) and childhood apraxia of speech (CAS); despite early evidence that speech perception may lead to error-prone motor planning/programming. In this study, we examine speech perception performance in school-age children with and without speech production deficits. Method: Speech perception was assessed using the Wide Range Acoustic Accuracy Scale to determine the just-noticeable difference in discrimination for three consonant-vowel syllable contrasts (/b[open back unrounded vowel]/-/w[open back unrounded vowel]/, /d[open back unrounded vowel]/-/g[open back unrounded vowel]/, /[voiced alveolar approximant][open back unrounded vowel]/-/w[open back unrounded vowel]/), each varying along a single acoustic parameter for seven children with CAS with rhotic errors, seven children with SSD with rhotic errors, and seven typically developing (TD) children. Results: Findings revealed statistically significant mean differences between perceptual performance of children with CAS when compared to TD children for discrimination of /[voiced alveolar approximant][open back unrounded vowel]/-/w[open back unrounded vowel]/ contrasts. Large effect sizes were also observed for comparisons of /[voiced alveolar approximant][open back unrounded vowel]/-/w[open back unrounded vowel]/ contrasts between children with CAS, SSD, and TD peers. Additionally, large effect sizes were observed for /d[open back unrounded vowel]/-/g[open back unrounded vowel]/ contrasts between children with CAS and SSD and TD children despite nonsignificant mean differences in group performance. Conclusions: Overall, mean outcome scores suggest that school-age children with CAS and persistent rhotic errors demonstrated less accurate speech perception skills relative to TD children for the /[voiced alveolar approximant][open back unrounded vowel]/-/w[open back unrounded vowel]/ contrasts. However, the relatively small sample sizes per group limit the extent to which these findings may be generalized to the broader population.

Background The success of cardiac auscultation varies widely among medical professionals, which can lead to missed treatments for structural heart disease. Applying machine learning to cardiac auscultation could address this problem, but despite recent interest, few algorithms have been brought to clinical practice. We evaluated a novel suite of Food and Drug Administration-cleared algorithms trained via deep learning on >15 000 heart sound recordings. Methods and Results We validated the algorithms on a data set of 2375 recordings from 615 unique subjects. This data set was collected in real clinical environments using commercially available digital stethoscopes, annotated by board-certified cardiologists, and paired with echocardiograms as the gold standard. To model the algorithm in clinical practice, we compared its performance against 10 clinicians on a subset of the validation database. Our algorithm reliably detected structural murmurs with a sensitivity of 85.6% and specificity of 84.4%. When limiting the analysis to clearly audible murmurs in adults, performance improved to a sensitivity of 97.9% and specificity of 90.6%. The algorithm also reported timing within the cardiac cycle, differentiating between systolic and diastolic murmurs. Despite optimizing acoustics for the clinicians, the algorithm substantially outperformed the clinicians (average clinician accuracy, 77.9%; algorithm accuracy, 84.7%.) Conclusions The algorithms accurately identified murmurs associated with structural heart disease. Our results illustrate a marked contrast between the consistency of the algorithm and the substantial interobserver variability of clinicians. Our results suggest that adopting machine learning algorithms into clinical practice could improve the detection of structural heart disease to facilitate patient care.

Broadly neutralizing antibodies (bnAbs) targeting the human immunodeficiency virus-1 (HIV-1) have played a crucial role in elucidating and characterizing neutralization-sensitive sites on the HIV-1 envelope spike and in informing vaccine development. Continual advancements in identifying more potent bnAbs, along with their capacity to trigger antibody-mediated effector functions, coupled with modifications to extend their half-life, position them as promising candidates for both HIV-1 treatment and prevention. While current pharmacological interventions have made significant progress in managing HIV-1 infection and enhancing quality of life, no definitive cure or vaccines have been developed thus far. Standard treatments involve daily oral anti-retroviral therapy, which, despite its efficacy, can lead to notable long-term side effects. Recent clinical trial data have demonstrated encouraging therapeutic and preventive potential for bnAb therapies in both HIV-1-infected individuals and those without the infection. This review provides an overview of the advancements in HIV-1-specific bnAbs and discusses the insights gathered from recent clinical trials regarding their application in treating and preventing HIV-1 infection.

Abstract Background Bone marrow stromal cells (BMSCs) are highly heterogeneous, which may reflect their diverse biological functions, including tissue maintenance, haematopoietic support and immune control. The current understanding of the mechanisms that drive the onset and resolution of heterogeneity, and how BMSCs influence other cells in their environment is limited. Here, we determined how the secretome and importantly the extracellular matrix of BMSCs can influence cellular phenotype. Methods We used two immortalised clonal BMSC lines isolated from the same heterogeneous culture as model stromal subtypes with distinct phenotypic traits; a multipotent stem-cell-like stromal line (Y201) and a nullipotent non-stem cell stromal line (Y202), isolated from the same donor BMSC pool. Label-free quantitative phase imaging was used to track cell morphology and migration of the BMSC lines over 96 h in colony-forming assays. We quantified the secreted factors of each cell line by mass spectrometry and confirmed presence of proteins in human bone marrow by immunofluorescence. Results Transfer of secreted signals from a stem cell to a non-stem cell resulted in a change in morphology and enhanced migration to more closely match stem cell-like features. Mass spectrometry analysis revealed a significant enrichment of extracellular matrix (ECM) proteins in the Y201 stem cell secretome compared to Y202 stromal cells. We confirmed that Y201 produced a more robust ECM in culture compared to Y202. Growth of Y202 on ECM produced by Y201 or Y202 restored migration and fibroblastic morphology, suggesting that it is the deficiency of ECM production that contributes to its phenotype. The proteins periostin and aggrecan, were detected at 71- and 104-fold higher levels in the Y201 versus Y202 secretome and were subsequently identified by immunofluorescence at rare sites on the endosteal surfaces of mouse and human bone, underlying CD271-positive stromal cells. These proteins may represent key non-cellular components of the microenvironment for bona-fide stem cells important for cell maintenance and phenotype in vivo. Conclusions We identified plasticity in BMSC morphology and migratory characteristics that can be modified through secreted proteins, particularly from multipotent stem cells. Overall, we demonstrate the importance of specific ECM proteins in co-ordination of cellular phenotype and highlight how non-cellular components of the BMSC microenvironment may provide insights into cell population heterogeneity and the role of BMSCs in health and disease.

Background For best efficacy, vaccines must provide long-lasting immunity. To measure longevity, memory from B and T cells are surrogate endpoints for vaccine efficacy. When antibodies are insufficient for protection, the immune response must rely on T cells. The magnitude and differentiation of effective, durable immune responses depend on antigen-specific precursor frequencies. However, development of vaccines that induce durable T-cell responses for cancer treatment has remained elusive.Methods To address long-lasting immunity, patients with HER2+ (human epidermal growth factor receptor 2) advanced stage cancer received HER2/neu targeted vaccines. Interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot measuring HER2/neu IFN-γ T cells were analyzed from 86 patients from three time points: baseline, 1 month after vaccine series, and long-term follow-up at 1 year, following one in vitro stimulation. The baseline and 1-month post-vaccine series responses were correlated with immunity at long-term follow-up by logistic regression. Immunity was modeled by non-linear functions using generalized additive models.Results Antigen-specific T-cell responses at baseline were associated with a 0.33-log increase in response at long-term follow-up, 95% CI (0.11, 0.54), p=0.003. 63% of patients that had HER2/neu specific T cells at baseline continued to have responses at long-term follow-up. Increased HER2/neu specific T-cell response 1 month after the vaccine series was associated with a 0.47-log increase in T-cell response at long-term follow-up, 95% CI (0.27, 0.67), p=2e-5. 74% of patients that had an increased IFN-γ HER2 response 1 month after vaccines retained immunity long-term. As the 1-month post-vaccination series precursor frequency of HER2+IFN-γ T-cell responses increased, the probability of retaining these responses long-term increased (OR=1.49 for every one natural log increase of precursor frequency, p=0.0002), reaching an OR of 20 for a precursor frequency of 1:3,000Conclusions Patients not destined to achieve long-term immunity can be identified immediately after completing the vaccine series. Log-fold increases in antigen-specific precursor frequencies after vaccinations correlate with increased odds of retaining long-term HER2 immune responses. Further vaccine boosting or immune checkpoint inhibitors or other immune stimulator therapy should be explored in patients that do not develop antigen-specific T-cell responses to improve overall response rates.

Despite the unique advantages of IgG3 over other IgG subclasses, such as mediating enhanced effector functions and increased flexibility in antigen binding due to a long hinge region, the therapeutic potential of IgG3 remains largely unexplored. This may be attributed to difficulties in recombinant expression and the reduced plasma half-life of most IgG3 allotypes. Here, we report plant expression of two SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding. P5C3 and H4-IgG1 mAbs were subclass-switched to IgG3 formats, designed for efficient production and increased PK values, carrying three allotypic variations, referred to as -WT, -H, and -KVH. A total of eight mAbs were produced in glycoengineered plants that synthesize fucose-free complex N-glycans with great homogeneity. Antigen, IgG-FcγR immune complex and complement binding studies demonstrated similar activities of all mAbs. In accordance, P5C3 Abs showed minor alterations in SARS-CoV-2 neutralization (NT) and antibody-dependent cell-mediated virus inhibition (ADCVI). Clear functional differences were observed between H4 variants with superior ADCVI and NT potencies of H4 IgG3 H. Our comparative study demonstrates the production of an IgG3 variant carrying an Fc domain with equivalent or enhanced functions compared to IgG3-WT, but with the stability and PK values ​​of IgG1. Our data also demonstrate that both allotypic variability and antibody specificity are important for fine-tuning of activities, an important information for the development of future therapeutics.

Mixed-methods research (MMR) holds promise for investigating several empirical questions within special education, capitalizing on the strengths of quantitative and qualitative traditions. We present an overview of MMR in special education and quality indicators for conducting and reporting such studies. We look to the future for how MMR may advance our understanding of crucial issues related to diversity, equity, and inclusion. Finally, we discuss special considerations for MMR and the open science movement.

Abstract Background Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare primary immunodeficiency, with only 256 cases reported globally. This study aimed to explore the disease burden of APDS from the perspective of individuals with APDS and their caregivers. Methods Qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers, to explore the symptoms and health-related quality of life (HRQoL) impact of APDS. Some individuals and caregivers also completed a narrative account exercise. All interviews were audio recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. Results Semi-structured qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers. Individuals and caregivers had the option of completing a narrative account exercise. Six HCPs participated in an interview. Seven participants completed the narrative account exercise (N = 5 caregivers and N = 2 individuals with APDS) and 12 took part in an interview (N = 4 caregivers and N = 8 individuals with APDS). Themes identified from HCPs interviews included symptoms, clinical manifestations, HRQoL impacts and treatments/management of APDS. The narrative account exercise identified similar themes, but with the addition to the journey to diagnosis. These themes were explored during the individual/caregiver interviews. Reported clinical manifestations and symptoms of APDS included susceptibility to infections, lymphoproliferation, gastrointestinal (GI) disorders, fatigue, bodily pain, and breathing difficulties. HRQoL impacts of living with APDS included negative impacts to daily activities, including work, education and social and leisure activities, physical functioning, as well as emotional well-being, such as concern for the future, and interpersonal relationships. Impacts to caregiver HRQoL included negative impacts to physical health, work, emotional well-being, interpersonal relationships and family life and holidays. The management of APDS included the use of healthcare services and medications including immunoglobulin replacement therapy (IRT), rapamycin, prophylactic antibiotics, leniolisib, as well as medical procedures due to complications. Conclusions APDS has a high disease burden and there is an unmet need for licensed, more targeted treatments which modify disease progression. This study was the first to describe the day-to-day experience and HRQoL impact of APDS from the perspective of individuals living with the condition, caregivers and treating physicians.

Abstract Lithium niobate is a promising material for developing quantum acoustic technologies due to its strong piezoelectric effect and availability in the form of crystalline thin films of high quality. However, at radio frequencies and cryogenic temperatures, these resonators are limited by the presence of decoherence and dephasing due to two-level systems. To mitigate these losses and increase device performance, a more detailed picture of the microscopic nature of these loss channels is needed. In this study, we fabricate several lithium niobate acoustic wave resonators and apply different processing steps that modify their surfaces. These treatments include argon ion sputtering, annealing, and acid cleans. We characterize the effects of these treatments using three surface-sensitive measurements: cryogenic microwave spectroscopy measuring density and coupling of TLS to mechanics, X-ray photoelectron spectroscopy and atomic force microscopy. We learn from these studies that, surprisingly, increases of TLS density may accompany apparent improvements in the surface quality as probed by the latter two approaches. Our work outlines the importance that surfaces and fabrication techniques play in altering acoustic resonator coherence, and suggests gaps in our understanding as well as approaches to address them.

Abstract Aberrations to metacognition—the ability to reflect on and evaluate self-performance—are a feature of poor mental health. Theoretical models of post-traumatic stress disorder propose that following severe stress or trauma, maladaptive metacognitive evaluations and appraisals of the event drive the development of symptoms. Empirical research is required in order to reveal whether disruptions to metacognition cause or contribute to symptom development in line with theoretical accounts, or are simply a consequence of ongoing psychopathology. In two experiments, using hierarchical Bayesian modelling of metacognition measured in a memory recognition task, we assessed whether distortions to metacognition occur at a state-level after an acute stress induction, and/or at a trait-level in a sample of individuals experiencing intrusive memories following traumatic stress. Results from experiment 1, an in-person laboratory-based experiment, demonstrated that heightened psychological responses to the stress induction were associated with poorer metacognitive efficiency, despite there being no overall change in metacognitive efficiency from pre- to post-stress (N = 27). Conversely, in experiment 2, an online experiment using the same metamemory task, we did not find evidence of metacognitive alterations in a transdiagnostic sample of patients with intrusive memory symptomatology following traumatic stress (N = 36, compared to 44 matched controls). Our results indicate a relationship between state-level psychological responses to stress and metacognitive alterations. The lack of evidence for pre- to post-stress differences in metamemory illustrates the importance for future studies to reveal the direction of this relationship, and consequently the duration of stress-associated metacognitive impairments and their impact on mental health.

Increasingly, mixed methods research (MMR) is used in special education, although the extent to which MMR is used in intervention research in the field of emotional/behavioral disorders (EBD) remains unknown. The purpose of this article is to examine the use of MMR in EBD intervention research to describe its application within the field. We conducted a targeted review of two prominent journals to assess the use of MMR over the last 20 years in the field. Following the identification of MMR intervention studies, we applied several frameworks to describe the application of MMR across identified studies. Results of this targeted review indicate that very few EBD intervention studies used MMR. Most studies used singular quantitative approaches (e.g., group experimental or single case research design) and only a small portion used qualitative methods. We did find a number of studies using multimethods by combining two or more quantitative approaches. Our assertion is that researchers consider increasing their use of MMR to advance the science in the field of EBD and to gain a better understanding of the "why" and "how" interventions are or are not effective.

The use of singular methodologies has dominated emotional and behavioral disorder (EBD) intervention research, and by extension, the field has not deployed mixed-methods research (MMR). The purpose of this article is to provide an overview of MMR and demonstrate its utility for conducting EBD intervention research. The basic tenants and design principles of MMR are discussed. Then, we present an aspirational framework that summarizes 17 areas where MMR can be applied to EBD intervention research using a school psychology study for illustration. The framework includes (a) research question development, (b) intervention development, (c) instrumentation development, (d) selection, (e) sampling, (f) multi-lens causality, (g) social validity, (h) acceptability, (i) stakeholder perspectives, (j) treatment integrity, (k) contamination, (l) carry-over effects, (m) outcome variability, (n) attrition, (o) replication, (p) data analysis and interpretation, and (q) dissemination. By referring to this framework as being aspirational, we mean to convey that very few social science studies or programs of research fully address all its elements; indeed, it may even be considered as a wish list. However, we contend that MMR approaches can help researchers to address the framework more fully within their lines of EBD inquiry.

Limited emotional and behavioral disorders (EBD)-focused intervention mixed methods research (MMR) has been published, particularly in top-tier EBD journals (i.e., "Behavior Disorders" and "Journal of Emotional and Behavioral Disorders"). The lack of published MMR creates what could be perceived as a Catch-22 situation wherein those who conduct EBD intervention research are not encouraged to conduct MMR because they do not see published examples in the journals that they read. The purpose of this article is to demonstrate how the routine use of MMR should be considered and suggest why doing so is a worthwhile endeavor. An overview of potential barriers to conducting intervention MMR in the field of EBD is provided. Examples of the use of MMR with Functional Behavior Analysis and Multi-tiered Systems of Support for students with Tier 2 needs are discussed. Details regarding the use of a mixed methods profile analysis to understand treatment successes and challenges are provided. Our hope is that this article will inspire EBD researchers to consider MMR as they develop interventions for children with EBD.

As a high-impact pedagogical practice, study abroad is frequently utilized as an internationalization strategy to build post-secondary students' global competence, but the impact of faculty-led short-term study abroad may vary widely across outcomes of interest. An understanding of student learning outcomes is especially needed now as COVID-19 begins to shift from pandemic to endemic and universities restart international initiatives. This systematic review synthesized and mapped evidence on global competence outcomes of short-term study abroad for undergraduate and graduate students. Studies (n=92) reported a total of 215 outcomes representing the three global competence domains of knowledge (41.4% of all outcomes), attitudes (38.1%), and skills (20.5%). Data sources used to assess global competence outcomes included self-administered surveys (40.1% of assessments), student journals (24.9%), and qualitative interviews (13.6%). While findings from this sample of studies offer evidence of positive impact of short-term study abroad on students' global competence, the substantive and methodological evidence gaps identified can help to build conceptual clarity and guide design of future assessment approaches.