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Occupational therapy practitioners address pain management across settings, populations, and the lifespan. Occupational therapy practitioners offer unique contributions to pain management through biopsychosocial approaches, targeting supported self-management and occupational engagement. Comprehensive pain education is necessary to prepare entry-level occupational therapy practitioners to address pain in practice, yet no standards exist in entry-level occupational therapy education. This survey describes the status of pain-related education in entry-level occupational therapy programs across the United States. A total of 41 entry-level occupational therapy programs completed the survey. Total instructional time for pain content was reported to be an average of 9.68 hours, ranging from 1 to 30 hours, indicating significant variability. Average lecture (4.88 hours) and lab-based (5.05 hours) time devoted to pain content were similar. More time was devoted to teaching pain interventions (4.91 hours) than pain assessments (2.82 hours). Most programs integrated pain content throughout the curriculum (73%). One program utilized a standardized pain curriculum (International Association for the Study of Pain Occupational Therapy Curriculum). Open-ended questions revealed a breadth of evidence-based resources, pain assessments, and interventions covering all domains of the biopsychosocial model of pain. The majority of faculty (61%) felt their current amount of pain education was insufficient, citing the need for increased time and educational activities for pain education across all program years. Given the essential and unique role of occupational therapy practitioners in pain management, improving pain education and practitioner competence is an important consideration across entry-level occupational therapy education. Further discussion is needed regarding educational standards and entry-level occupational therapy curricula relating to pain management.

The use of high-fidelity simulation and standardized patients (SPs) in occupational therapy (OT) education is expanding. However, the implementation of simulation varies across programs, leading to inconsistent outcomes and research limitations. Furthermore, details on SP use and training are lacking in OT literature. This article aims to provide OT educators with considerations for improving simulation fidelity by effectively using highly trained SPs. For example, recruiting SPs from diverse backgrounds is necessary to improve sociological fidelity, and proper training of SPs is required to ensure psychological fidelity. This article also emphasizes the need for standardized training for SPs and recommends following the Association of Standardized Patient Educators (ASPE) guidelines to ensure best practices in OT education. Adequate SP training and ongoing professional development are essential for maintaining simulation fidelity during SP experiences and optimizing student learning outcomes. Implementing SP experiences within the OT curriculum, SP recruitment and training, case development, pre-briefing, and debriefing processes are discussed, with recommendations from current evidence and the authors' experience at an institution accredited by the Society for Simulation in Healthcare. Trained SPs can enhance simulation fidelity and provide students with realistic and compelling learning experiences, better preparing them for fieldwork and clinical practice. While further research is needed to explore the efficacy of SP encounters in OT education and the student experience, this article reinforces the need to standardize the use and training of SPs to enhance simulation fidelity and support the reliability and validity of future research efforts surrounding the use of SPs.

Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibited viscoelastic liquid behavior and that mucus secreted by IL-13-activated HAECs exhibited solid-like behavior caused by mucin cross-linking. In addition, IL-13-activated HAECs shows increased peroxidase activity in apical secretions, and an overlaid thiolated polymer (thiomer) solution shows an increase in solid behavior that was prevented by peroxidase inhibition. Furthermore, gene expression for thyroid peroxidase (TPO), but not lactoperoxidase (LPO), was increased in IL-13-activated HAECs and both TPO and LPO catalyze the formation of oxidant acids that cross-link thiomer solutions. Finally, gene expression for TPO in airway epithelial brushings was increased in patients with asthma with high airway mucus plug scores. Together, our results show that IL-13-activated HAECs autonomously generated pathologic mucus via peroxidase-mediated cross-linking of mucin polymers.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

PurposePresent knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning-based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate.Methods and materialsThe EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors.ResultsA total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes.ConclusionsOur results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ("stubby", ≤12 mm) and long ("stringy", >12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.

The commencement of a new editorial tenure within the Journal of Personality and Social Psychology: Attitudes and Social Cognition (JPSP: ASC) provides an opportunity for reflection regarding the journal's core mission. The editors recognize that social psychology is at a crossroads due to competing demands that may have led to reduced submissions and posed challenges for previous editors in filling the journal's pages. Now, JPSP: ASC has been allotted more pages to allow for growth during this editorial term. Although this is desirable for the field, it adds to the pressure of identifying articles for publication given the difficulties filling the pages during previous editorial terms. As the premier outlet of social psychology since 1965, JPSP: ASC will retain its centrality if we increase submissions and publish more articles, while continuing to strive to communicate methodologically trustworthy, intellectually stimulating, and socially relevant research, in a responsible fashion. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mathematical models supported by a robust automated data pipeline proved to be useful tools for a data-driven and science-based response and policy-making during the COVID-19 pandemic in the Philippines. In the first year of the pandemic, FASSSTER (Feasibility Analysis on Syndromic Surveillance using Spatio-Temporal Epidemiological modeleR) used a compartmental model to generate scenario-based projections of COVID-19 cases. The emergence of the Delta variant, however, and the administration of vaccines over the second half of 2021 caused significant changes in the Philippine pandemic landscape. This necessitated making adjustments to the model to better capture the local disease transmission dynamics and address policy questions posed by stakeholders regarding COVID-19 over that period. The extended model was then utilized to generate case projections by applying different intervention scenarios, specifically, scenarios involving vaccination coverage, compliance to public health standards and active detection of cases. The new model demonstrated reliability in terms of capturing historical data and in producing relatively accurate short-term projections. In turn, most of the projections generated by the model had been used in support of case monitoring and policy-making in the country. This paper illustrates the significance of enhancing mathematical models in response to the dynamic nature of the COVID-19 pandemic.

Aim: To explore the lived-in experiences of primary caregivers of children with mental illness while taking care during the coronavirus disease 2019 (COVID-19) pandemic. Methodology: This study is a descriptive phenomenological study. Convenience sampling was used. Data were collected by in-depth interviews of 30 primary caregivers of children with mental illness, during the COVID-19 pandemic. All interviews were audio-recorded and analyzed using a thematic approach. Results: The overall aura of fear and panic brought by the pandemic found its way into the psyche of patients and the development of their illnesses during the pandemic. The entirety of the work brought out three themes and 11 subthemes as categorized for the aim of this study. Conclusion: Primary caregivers of children with mental illness during the COVID-19 pandemic reveal that lifestyle changes, such as online education, confinement, overuse of electronic gadgets, and increased laziness and lethargy in children after prolonged lockdown, were drastic changes which caregivers had to deal with.

Abstract Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with survival) across different regions within a tumor were more prognostic than the average expression. Following that, we examined whether multiregional expression profiling can improve the performance of prognostic signatures. We investigated 11 gene signatures collected from previous publications and one signature developed in this study. For all of them, the prognostic prediction accuracy can be significantly improved by converting the regional expression of signature genes into sample-specific expression with a simple function—taking the maximal expression of hazardous genes and the minimal expression of protective genes. In the tumor microenvironment, we found a similar rule also seems applicable to immune ITH. We calculated the infiltration levels of major immune cell types in each region of a sample based on expression deconvolution. Prognostic analysis indicated that the region with the lowest infiltration level of protective or highest infiltration level of hazardous immune cells determined the prognosis of NSCLC patients. Our study highlighted the impact of RNA-ITH on the prognostication of NSCLC, which should be taken into consideration to optimize the design and application of expression-based prognostic biomarkers and models. Multiregional assays have the great potential to significantly improve their applications to prognostic stratification.

Abstract ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 insertion Y772_A775dupYVMA was the most frequent alteration (58% vs 41.6% in the Chinese vs the US), followed by G776delinsVC/LC/VV/IC (10.7% vs 9.7%), and S310X (10.5% vs 15.4%). EGFR ex20 insertions were identified in the A767-V774 region, whereas ERBB2 ex20 insertions were observed in the Y772-P780 region. Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.