Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.

Effects of cognitive behavioural therapy and bright light therapy for insomnia in youths with eveningness: study protocol for a randomised controlled trial.

BACKGROUND: Insomnia and eveningness are common and often comorbid conditions in youths. While cognitive behavioural therapy for insomnia (CBT-I) has been suggested as a promising intervention, it remains unclear whether it is sufficient to also address circadian issues in youths. In addition, despite that light has been shown to be effective in phase-shifting one's circadian rhythm, there has been limited data on the effects of bright light therapy and its combination with CBT-I on sleep and circadian outcomes in youths. The current protocol outlines a randomised controlled trial that examines the efficacy of CBT-I and CBT-I plus bright light therapy (BLT) in reducing insomnia severity, improving mood symptoms and daytime functioning (e.g. sleepiness, fatigue, cognitive function), and improving subjective and objective sleep and circadian measures compared to a waitlist control group. METHODS: We will carry out a randomised controlled trial (RCT) with 150 youths aged 12-24 who meet the criteria of insomnia and eveningness. Participants will be randomised into one of three groups: CBT-I with bright light therapy, CBT-I with placebo light, and waitlist control. Six sessions of CBT-I will be delivered in a group format, while participants will be currently asked to use a portable light device for 30 min daily immediately after awakening throughout the intervention period for bright light therapy. The CBT-I with light therapy group will receive bright constant green light (506 lx) while the CBT-I with placebo light group will receive the modified light device with the LEDs emitting less than 10 lx. All participants will be assessed at baseline and post-treatment, while the two active treatment groups will be additionally followed up at 1 month and 6 months post-intervention. The primary outcome will be insomnia severity, as measured by the Insomnia Severity Index. Secondary outcomes include self-reported mood, circadian, daytime functioning, and quality of life measures, as well as sleep parameters derived from actigraphy and sleep diary and neurocognitive assessments. Objective measures of the circadian phase using dim-light melatonin onset assessment and sleep parameters using polysomnography will also be included as the secondary outcomes. DISCUSSION: This study will be the first RCT to directly compare the effects of CBT-I and BLT in youths with insomnia and eveningness. Findings from the study will provide evidence to inform the clinical management of insomnia problems and eveningness in youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT04256915. Registered on 5 February 2020.

Secular trends in sleep and circadian problems among adolescents in Hong Kong: From 2011-2012 to 2017-2019.

OBJECTIVE: The study aimed to investigate secular trends in sleep and circadian problems in Hong Kong Chinese adolescents. METHODS: This study analyzed cross-sectional data from two large-scale school-based sleep surveys conducted in 2011-2012 and 2017-2019. Sleep and circadian problems, including sleep-wake pattern, insomnia, chronotype, social jetlag, daytime sleepiness, and other sleep-related factors, were compared between two survey years. RESULTS: A total of 8082 adolescents (5639 students in 2011-2012 [Mean age: 14.4 years, 50.9% boys] and 2443 students in 2017-2019 [Mean age: 14.7 years, 54.0% boys]) were included in this 7-year study. The average time in bed of Hong Kong adolescents decreased from 8.38 hours to 8.08 hours from 2011-2012 to 2017-2019. There was a 0.28-hour delay in weekday bedtime, 0.54-hour advance in weekend wake-up time, and a 0.36-hour decline in average time in bed, resulting in increased trends of sleep loss (Time in bed <8h: OR = 2.06, 95%CI: 1.44-2.93, p < 0.01; Time in bed <7h: OR = 2.73, 95%CI: 1.92-3.89, p < 0.01), daytime sleepiness (OR = 1.70, 95%CI: 1.34-2.16, p < 0.01), and evening chronotype (OR = 1.26, 95%CI: 1.08-1.48, p < 0.01). The increased trend in insomnia disorder, however, was insignificant when covariates were adjusted. CONCLUSION: A secular trend of reduced time in bed, delay in weekday bedtime, advance in weekend wake-up time, increase in evening chronotype and daytime sleepiness from 2011-2012 to 2017-2019 were observed. There is a timely need for systematic intervention to promote sleep health in adolescents.

Ophthalmologic Presentations of Incontinentia Pigmenti.

Purpose: To characterize treatments and outcomes in incontinentia pigmenti. Methods: Cases of incontinentia pigmenti were consecutively identified from a retina practice. Inclusion criteria were patients with incontinentia pigmenti with at least 6 months of follow-up. All patients had a full ophthalmic examination, including imaging with widefield fundus photography and widefield fluorescein angiography. Eyes with areas of avascular retina were treated with laser photocoagulation (except for 1 eye with mild changes). Results: Thirty-six eyes of 18 patients with incontinentia pigmenti were included. The median age at presentation was 11 months. On presentation, 7 eyes had a visual acuity (VA) of 20/40 or better and 3 eyes had VA of 20/50 to 20/100. The remaining 26 eyes could fix and follow or had at least light perception (LP) VA given the patients' young age. Of the 36 eyes, 20 (56%) had retinal involvement. The mean follow-up for treated patients was 6.9 years. Seventy-four percent of treated eyes required 1 laser session only. No eye that received laser treatment subsequently developed a retinal detachment. Of the 26 eyes with initial fix-and-follow or LP VA, 12 had Snellen or Allen VA testing at follow-up. Nine of these eyes had a follow-up VA of 20/40 or better. Of 10 eyes with a Snellen or Allen VA recorded at the initial visit, 9 had a final VA that was the same or improved. Conclusions: Laser photocoagulation was effective in treating patients with retinal manifestations of incontinentia pigmenti. Except for 1 eye, VA remained stable at the final follow-up.

An Open-Label Pilot Trial of a Brief, Parent-Based Sleep Intervention in Children With ADHD.

OBJECTIVE: To assess the effects of a brief parent-based behavioral sleep intervention in children with ADHD. METHODS: Families with a child with ADHD and parent-reported sleep problems received a brief parent-based sleep intervention, which involved two one-to-one consultation sessions and one telephone follow-up with the parent/caregiver. Child's sleep and clinical symptoms, and parental sleep and daytime functioning were assessed at baseline, 2-week post-intervention, and 3-month follow-up. RESULTS: Sixty eligible families (mean age of the child: 9.4 ± 1.5 years; boys: 75%) were recruited, and 43 (72%) completed the whole intervention. The intervention resulted in significant improvements in the child's sleep, clinical symptoms, and parental sleep and parenting stress, and these improvements were generally maintained at 3-month follow-up. CONCLUSION: The findings supported the promising effects of a brief parent-based sleep intervention on improving sleep and clinical symptoms in children with ADHD and parental sleep and parenting stress. Further randomized clinical trials with long-term follow-up are needed to test the robustness of the effectiveness of the intervention.

Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.

Cancer progression can be restrained by tumor-infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre-wired, in which innate lymphocytes and innate-like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming-dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming-dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell-directed therapeutic programs, recent studies have revealed that pre-wired cancer immunity mediated by tissue-resident type 1 innate lymphoid cells (ILC1s) and killer innate-like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer-sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed.

Mitochondrial Raf1 Regulates Glutamine Catabolism.

Raf kinases play vital roles in normal mitogenic signaling and cancer, however, the identities of functionally important Raf-proximal proteins throughout the cell are not fully known. Raf1 proximity proteomics/BioID in Raf1-dependent cancer cells unexpectedly identified Raf1-adjacent proteins known to reside in the mitochondrial matrix. Inner-mitochondrial localization of Raf1 was confirmed by mitochondrial purification and super-resolution microscopy. Inside mitochondria, Raf1 associated with glutaminase (GLS) in diverse human cancers and enabled glutaminolysis, an important source of biosynthetic precursors in cancer. These impacts required Raf1 kinase activity and were independent of canonical MAP kinase pathway signaling. Kinase-dead mitochondrial matrix-localized Raf1 impaired glutaminolysis and tumorigenesis in vivo. These data indicate that Raf1 localizes inside mitochondria where it interacts with GLS to engage glutamine catabolism and support tumorigenesis.

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.

Effects of childhood obstructive sleep apnea with and without daytime sleepiness on behaviors and emotions.

OBJECTIVE: To investigate the relationship between obstructive sleep apnea (OSA) with and without excessive daytime sleepiness (EDS) and behavioral and emotional outcomes in non-obese prepubertal children. METHODS: This was a retrospective analysis of children aged 5-11 years who presented to our unit for assessment of their sleep-related complaints. All children underwent polysomnography (PSG). They also completed the Pediatric Daytime Sleepiness Scale (PDSS) and a sleep diary. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was ≥1 event/hour. EDS was defined as PDSS >15. Behavioral and emotional outcomes were assessed using the Child Behavioral Checklist (CBCL). RESULTS: Data from 391 children (mean age of 8.6 ± 1.7 years; 67 % male) were analyzed. Seventy children did not have OSA or EDS, 137 had OSA, 50 had reported having EDS but without OSA, and 134 children had both OSA and EDS. There were significantly higher CBCL total problems score in the combined group (61 ± 9) compared to the non-OSA/EDS group (54 ± 10), and the OSA-only group (54 ± 10) (p < 0.001). The presence of EDS was significantly associated with higher CBCL T score and higher odds for clinically significant behavioral problems (T score ≥65) after adjusting for age, sex, BMI z-score and average sleep duration (p < 0.001). CONCLUSION: Excessive daytime sleepiness is an important contributory factor associated with suboptimal behavioral and emotional outcomes in children with OSA.

Which Localizing Strategy is the Most Cost-Effective in Reoperative Primary Hyperparathyroidism?

INTRODUCTION: 2%-10% of patients with primary hyperparathyroidism (PHPT) who undergo parathyroidectomy develop persistent/recurrent disease. The aim of this study was to determine which preoperative localization method is most cost-effective in reoperative PHPT. METHODS: Clinical decision analytic models comparing cost-effectiveness of localizing studies in reoperative PHPT were constructed using TreeAge Pro. Cost and probability assumptions were varied via Probabilistic Sensitivity Analysis (PSA) to test the robustness of the base case models. RESULTS: Base case analysis of model 1 revealed ultrasound (US)-guided fine-needle aspiration with PTH assay as most cost-effective after localizing US. This was confirmed on PSA of model 1. Model 2 showed four-dimensional computed tomography (4D-CT) as most cost-effective after negative US. If not localized by US, on PSA, 4D-CT was the next most cost-effective test. CONCLUSIONS: US-guided FNA with PTH is the most cost-effective confirmatory test after US localization. 4D-CT should be considered as the next best test after negative US.

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G.

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC â€‹= â€‹0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

Polymorphisms Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease Influence the Progression of End-Stage Liver Disease.

BACKGROUND AND AIMS: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored. METHODS: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD. RESULTS: Distinct sets of factors are associated with the progression to ESLD. The PNPLA3 rs738409:G and TM6SF2 rs58542926:T alleles, body mass index (BMI), age, and female sex were positively associated with progression from a healthy state to MASH. The PNPLA3 rs738409:G allele, age, male sex, and having type 2 diabetes mellitus were positively associated, while BMI was negatively associated with progression from MASH to MASLD-associated ESLD. The PNPLA3 rs738409:G and GCKR rs780094:T alleles, age, and male sex were positively associated, while BMI was negatively associated with progression from a healthy state to ALD-associated ESLD. The findings indicate that the PNPLA3 rs738409:G allele increases susceptibility to ESLD regardless of etiology, the TM6SF2 rs58542926:T allele increases susceptibility to MASH, and the GCKR rs780094:T allele increases susceptibility to ALD-associated ESLD. CONCLUSION: The PNPLA3, TM6SF2, and GCKR minor alleles influence the progression of MASLD-associated or ALD-associated ESLD. Genotyping for these variants in MASLD and ALD patients can enhance risk assessment, prompting early interventions to prevent ESLD.

Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.

The interplay between metabolism and chromatin signaling is implicated in cancer progression. However, whether and how metabolic reprogramming in tumors generates chromatin vulnerabilities remain unclear. Lung adenocarcinoma (LUAD) tumors frequently harbor aberrant activation of the NRF2 antioxidant pathway, which drives aggressive and chemo-resistant disease. Using a chromatin-focused CRISPR screen, we report that NRF2 activation sensitizes LUAD cells to genetic and chemical inhibition of class I histone deacetylases (HDACs). This association is observed across cultured cells, mouse models, and patient-derived xenografts. Integrative epigenomic, transcriptomic, and metabolomic analysis demonstrates that HDAC inhibition causes widespread redistribution of H4ac and its reader protein, which transcriptionally downregulates metabolic enzymes. This results in reduced flux into amino acid metabolism and de novo nucleotide synthesis pathways that are preferentially required for the survival of NRF2-active cancer cells. Together, our findings suggest NRF2 activation as a potential biomarker for effective repurposing of HDAC inhibitors to treat solid tumors.

Epigenetic priming targets tumor heterogeneity to shift transcriptomic phenotype of pancreatic ductal adenocarcinoma towards a Vitamin D susceptible state.

As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state. Increasing overall H3K27 acetylation with GTA and reducing overall DNA methylation with 5-Aza not only elevated the Vitamin D receptor (VDR) expression but also reprogrammed the Vitamin D-responsive genes. Consequently, Vitamin D inhibited cell viability and migration in the epigenetically primed PDAC cells by activating genes involved in apoptosis as well as genes involved in negative regulation of cell proliferation and migration, while the opposite effect of Vitamin D was observed in unprimed cells. Studies in genetically engineered mouse PDAC cells further validated the effects of epigenetic priming for enhancing the anti-tumor activity of Vitamin D. Using gain- and loss-of-function experiments, we further demonstrated that VDR expression was necessary but not sufficient for activating the favorable transcriptomic phenotype in respond to Vitamin D treatment in PDAC, highlighting that both the VDR and Vitamin D-responsive genes were prerequisites for Vitamin D response. These data reveal a previously undefined mechanism in which epigenetic state orchestrates the expression of both VDR and Vitamin D-responsive genes and determines the therapeutic response to Vitamin D in PDAC.

A systematic review and meta-analysis of how social memory is studied.

Social recognition is crucial for survival in social species, and necessary for group living, selective reproduction, pair bonding, and dominance hierarchies. Mice and rats are the most commonly used animal models in social memory research, however current paradigms do not account for the complex social dynamics they exhibit in the wild. To assess the range of social memories being studied, we conducted a systematic analysis of neuroscience articles testing the social memory of mice and rats published within the past two decades and analyzed their methods. Our results show that despite these rodent's rich social memory capabilities, the majority of social recognition papers explore short-term memories and short-term familiarity levels with minimal exposure between subject and familiar stimuli-a narrow type of social memory. We have identified several key areas currently understudied or underrepresented: kin relationships, mates, social ranks, sex variabilities, and the effects of aging. Additionally, reporting on social stimulus variables such as housing history, strain, and age, is limited, which may impede reproducibility. Overall, our data highlight large gaps in the diversity of social memories studied and the effects social variables have on social memory mechanisms.

Survey of Retina Specialists' Attitudes and Practice Patterns of Screening and Management of Candida Endophthalmitis.

PURPOSE: To understand retina specialists' attitudes and practice patterns for screening for and managing Candida endophthalmitis and any impact of the COVID-19 pandemic on these practice patterns. METHODS: A survey was developed on Survey Monkey and distributed to ASRS regular members via email in April 2021. RESULTS: The survey had 231 respondents, of whom 169 (73%) performed inpatient consultations. Ninety percent responded that they do not recommend routinely screening asymptomatic patients with candidemia. For unresponsive patients with candidemia that lack visible signs of endophthalmitis, 65% did not recommend routine screening.However, 85% reported their affiliated hospitals did not have a policy to defer such screening consultations; this proportion did not significantly change when asked if a policy was implemented in response to the COVID-19 pandemic.For patients with a dilated examination without signs of endophthalmitis, 89% surveyed recommended continuing systemic antifungals and reconsult PRN, while the remainder recommended repeat examinations until off antifungals. For initial management of Candida endophthalmitis, 55% indicated systemic antifungals only; 43% indicated systemic antifungals with tap & inject, and 2% indicated systemic antifungals with vitrectomy and intravitreal antifungals. CONCLUSION: A discordance exists between the prevailing opinion among retina specialists against routine Candida endophthalmitis screening and hospital consultation policies, which were not significantly impacted by the COVID-19 pandemic. In cases of diagnosed endogenous endophthalmitis, slightly more than half of surveyed retina specialists would not initiate additional treatment beyond systemic antifungals while just under half surveyed recommended initial tap and inject in addition to systemic antifungals.

Subtyping at-risk adolescents for predicting response toward insomnia prevention program.

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.

AI Deployment on GBM Diagnosis: A Novel Approach to Analyze Histopathological Images Using Image Feature-Based Analysis.

BACKGROUND: Glioblastoma (GBM) is one of the most common malignant primary brain tumors, which accounts for 60-70% of all gliomas. Conventional diagnosis and the decision of post-operation treatment plan for glioblastoma is mainly based on the feature-based qualitative analysis of hematoxylin and eosin-stained (H&E) histopathological slides by both an experienced medical technologist and a pathologist. The recent development of digital whole slide scanners makes AI-based histopathological image analysis feasible and helps to diagnose cancer by accurately counting cell types and/or quantitative analysis. However, the technology available for digital slide image analysis is still very limited. This study aimed to build an image feature-based computer model using histopathology whole slide images to differentiate patients with glioblastoma (GBM) from healthy control (HC). METHOD: Two independent cohorts of patients were used. The first cohort was composed of 262 GBM patients of the Cancer Genome Atlas Glioblastoma Multiform Collection (TCGA-GBM) dataset from the cancer imaging archive (TCIA) database. The second cohort was composed of 60 GBM patients collected from a local hospital. Also, a group of 60 participants with no known brain disease were collected. All the H&E slides were collected. Thirty-three image features (22 GLCM and 11 GLRLM) were retrieved from the tumor volume delineated by medical technologist on H&E slides. Five machine-learning algorithms including decision-tree (DT), extreme-boost (EB), support vector machine (SVM), random forest (RF), and linear model (LM) were used to build five models using the image features extracted from the first cohort of patients. Models built were deployed using the selected key image features for GBM diagnosis from the second cohort (local patients) as model testing, to identify and verify key image features for GBM diagnosis. RESULTS: All five machine learning algorithms demonstrated excellent performance in GBM diagnosis and achieved an overall accuracy of 100% in the training and validation stage. A total of 12 GLCM and 3 GLRLM image features were identified and they showed a significant difference between the normal and the GBM image. However, only the SVM model maintained its excellent performance in the deployment of the models using the independent local cohort, with an accuracy of 93.5%, sensitivity of 86.95%, and specificity of 99.73%. CONCLUSION: In this study, we have identified 12 GLCM and 3 GLRLM image features which can aid the GBM diagnosis. Among the five models built, the SVM model proposed in this study demonstrated excellent accuracy with very good sensitivity and specificity. It could potentially be used for GBM diagnosis and future clinical application.

Development, Reliability, and Structural Validity of the Scale for Knowledge, Attitude, and Practice in Ethics Implementation Among AI Researchers: Cross-Sectional Study.

BACKGROUND: Medical artificial intelligence (AI) has significantly contributed to decision support for disease screening, diagnosis, and management. With the growing number of medical AI developments and applications, incorporating ethics is considered essential to avoiding harm and ensuring broad benefits in the lifecycle of medical AI. One of the premises for effectively implementing ethics in Medical AI research necessitates researchers' comprehensive knowledge, enthusiastic attitude, and practical experience. However, there is currently a lack of an available instrument to measure these aspects. OBJECTIVE: The aim of this study was to develop a comprehensive scale for measuring the knowledge, attitude, and practice of ethics implementation among medical AI researchers, and to evaluate its measurement properties. METHODS: The construct of the Knowledge-Attitude-Practice in Ethics Implementation (KAP-EI) scale was based on the Knowledge-Attitude-Practice (KAP) model, and the evaluation of its measurement properties was in compliance with the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) reporting guidelines for studies on measurement instruments. The study was conducted in 2 phases. The first phase involved scale development through a systematic literature review, qualitative interviews, and item analysis based on a cross-sectional survey. The second phase involved evaluation of structural validity and reliability through another cross-sectional study. RESULTS: The KAP-EI scale had 3 dimensions including knowledge (10 items), attitude (6 items), and practice (7 items). The Cronbach α for the whole scale reached .934. Confirmatory factor analysis showed that the goodness-of-fit indices of the scale were satisfactory (χ2/df ratio:=2.338, comparative fit index=0.949, Tucker Lewis index=0.941, root-mean-square error of approximation=0.064, and standardized root-mean-square residual=0.052). CONCLUSIONS: The results show that the scale has good reliability and structural validity; hence, it could be considered an effective instrument. This is the first instrument developed for this purpose.