Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis.

OBJECTIVE: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. METHODS: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49). RESULTS: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91). INTERPRETATION: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.

Phylogeny and species delimitation of ciliates in the genus Spirostomum (Class, Heterotrichea) using single-cell transcriptomes.

Ciliates are single-celled microbial eukaryotes that diverged from other eukaryotic lineages over a billion years ago. The extensive evolutionary timespan of ciliate has led to enormous genetic and phenotypic changes, contributing significantly to their high level of diversity. Recent analyses based on molecular data have revealed numerous cases of cryptic species complexes in different ciliate lineages, demonstrating the need for a robust approach to delimit species boundaries and elucidate phylogenetic relationships. Heterotrich ciliate species of the genus Spirostomum are abundant in freshwater and brackish environments and are commonly used as biological indicators for assessing water quality. However, some Spirostomum species are difficult to identify due to a lack of distinguishable morphological characteristics, and the existence of cryptic species in this genus remains largely unexplored. Previous phylogenetic studies have focused on only a few loci, namely the ribosomal RNA genes, alpha-tubulin, and mitochondrial CO1. In this study, we obtained single-cell transcriptome of 25 Spirostomum species populations (representing six morphospecies) sampled from South Korea and the USA, and used concatenation- and coalescent-based methods for species tree inference and delimitation. Phylogenomic analysis of 37 Spirostomum populations and 265 protein-coding genes provided a robustious insight into the evolutionary relationships among Spirostomum species and confirmed that species with moniliform and compact macronucleus each form a distinct monophyletic lineage. Furthermore, the multispecies coalescent (MSC) model suggests that there are at least nine cryptic species in the Spirostomum genus, three in S. minus, two in S. ambiguum, S. subtilis, and S. teres each. Overall, our fine sampling of closely related Spirostomum populations and wide scRNA-seq allowed us to demonstrate the hidden crypticity of species within the genus Spirostomum, and to resolve and provide much stronger support than hitherto to the phylogeny of this important ciliate genus.

Cumulative lifetime stressor exposure impairs stimulus-response but not contextual learning.

Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions.

A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS to promote normal mitochondrial morphology and respiratory function. Mmc1 is a distant relative of the dynamin superfamily of proteins (DSPs), GTPases, which are well established to shape and remodel membranes. Similar to DSPs, Mmc1 self-associates and forms high-molecular-weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting that it does not dynamically remodel membranes. These data are consistent with the model that Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.

Impulsivity in fatal suicide behaviour: A systematic review and meta-analysis of psychological autopsy studies.

Our aim is to review and perform a meta-analysis on the role of impulsivity in fatal suicide behaviour. We included papers who used psychological autopsy methodology, assessed adult death by suicide, and included assessment of impulsivity. We excluded papers about assisted suicide, terrorist suicide, or other cause of death other than suicide or postmortem diagnosis made only from medical records or database. 97 articles were identified. 33 were included in the systematic review and nine in the meta-analysis. We found that people who die by suicide with high impulsivity are associated with younger age, substance abuse, and low intention to die, whereas those with low impulsivity were associated with older age, depression, schizophrenia, high intention to die and low social support. In the meta-analysis, suicide cases had higher impulsivity scores than living controls (Hedges' g = 0.59, 95 % CI [0.28, 0.89], p=.002). However, studies showed heterogeneity (Q = 90.86, p<.001, I2=89.0 %). Impulsivity-aggressiveness interaction was assessed through meta-regression (ß=0.447, p=.045). Individuals with high impulsivity would be exposed to a higher risk of fatal suicide behaviour, aggressiveness would play a mediating role. People who die by suicide with high and low impulsivity display distinct characteristics, which may reflect different endophenotypes leading to suicide by different pathways.

Innate immune activation in neurodegenerative diseases.

Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).

Performance evaluation of the FastIC readout ASIC with emphasis on Cherenkov emission in TOF-PET.

Objective.The efficient usage of prompt photons like Cherenkov emission is of great interest for the design of the next generation, cost-effective, and ultra-high-sensitivity time-of-flight positron emission tomography (TOF-PET) scanners. With custom, high power consuming, readout electronics and fast digitization the prospect of sub-300 ps FWHM with PET-sized BGO crystals have been shown. However, these results are not scalable to a full system consisting of thousands of detector elements.Approach.To pave the way toward a full TOF-PET scanner, we examine the performance of the FastIC ASIC with Cherenkov-emitting scintillators (BGO), together with one of the most recent SiPM detector developments based on metal trenching from FBK. The FastIC is a highly configurable ASIC with 8 input channels, a power consumption of 12 mW ch-1and excellent linearity on the energy measurement. To put the timing performance of the FastIC into perspective, comparison measurements with high-power consuming readout electronics are performed.Main results.We achieve a best CTR FWHM of 330 ps for 2 × 2 × 3 mm3and 490 ps for 2 × 2 × 20 mm3BGO crystals with the FastIC. In addition, using 20 mm long LSO:Ce:Ca crystals, CTR values of 129 ps FWHM have been measured with the FastIC, only slightly worse to the state-of-the-art of 95 ps obtained with discrete HF electronics.Significance.For the first time, the timing capability of BGO with a scalable ASIC has been evaluated. The findings underscore the potential of the FastIC ASIC in the development of cost-effective TOF-PET scanners with excellent timing characteristics.

Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives: This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design: Retrospective consecutive patient cohort analysis. Methods: We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results: During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion: EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Outcome and approach of small-bowel stricture dilation using balloon-assisted endoscopy in patients with Crohn's disease This study investigated the safety and success of using balloon-assisted endoscopy as a method to dilate small bowel strictures in patients with Crohn's disease. As a secondary outcome, we compared the overall safety and success between two different types of endoscopic systems: the single- and double-balloon systems.

Triadic Approximation Reveals the Role of Interaction Overlap on the Spread of Complex Contagions on Higher-Order Networks.

Contagion processes relying on the exposure to multiple sources are prevalent in social systems, and are effectively represented by hypergraphs. In this Letter, we derive a mean-field model that goes beyond node- and pair-based approximations. We reveal how the stability of the contagion-free state is decided by either two- or three-body interactions, and how this is strictly related to the degree of overlap between these interactions. Our findings demonstrate the dual effect of increased overlap: it lowers the invasion threshold, yet produces smaller outbreaks. Corroborated by numerical simulations, our results emphasize the significance of the chosen representation in describing a higher-order process.

The energetic costs of cellular complexity in evolution.

The evolutionary history of cells has been marked by drastic increases in complexity. Some hypothesize that such cellular complexification requires a massive energy flux as the origin of new features is hypothetically more energetically costly than their evolutionary maintenance. However, it remains unclear how increases in cellular complexity demand more energy. I propose that the early evolution of new genes with weak functions imposes higher energetic costs by overexpression before their functions are evolutionarily refined. In the long term, the accumulation of new genes deviates resources away from growth and reproduction. Accrued cellular complexity further requires additional infrastructure for its maintenance. Altogether, this suggests that larger and more complex cells are defined by increased survival but lower reproductive capacity.

A Study on the Efficacy and Safety of Pipeline Shield Stents and Nonmodified Surface Flow-Diverting Stents in Patients with Intracranial Aneurysms.

BACKGROUND: Few studies have compared the Pipeline Shield stents with previous generations of flow-diverting stents (FDSs) for the treatment of unruptured intracranial aneurysms. This study aimed to evaluate the efficacy and safety of Pipeline Shield stents and FDSs without modified surfaces. METHODS: The present evaluation is a retrospective cohort study of patients endovascularly treated with Pipeline Shield stents or FDSs without modified surfaces for unruptured intracranial aneurysms between January 2014 and June 2022. The data analyzed were obtained from the anonymized database of our institution's interventional radiology service. RESULTS: A total of 147 patients with 155 unruptured intracranial aneurysms were included. Of the 155 aneurysms, 96 were treated with Pipeline Shield stents and 59 with FDSs without modified surfaces. The aneurysms treated with Pipeline Shield stents had higher 6-month (O'Kelly-Marotta [OKM] D; 87.5% vs. 71.4%; P = 0.025) and 1-year (OKM D; 82.5% vs. 63.0%; P = 0.047) occlusion rates than the aneurysms treated using FDSs without modified surfaces. No differences between the devices were found at the 1-year follow-up in the incidence of ischemic stroke (P = 0.939) or hemorrhagic complications (P = 0.559). CONCLUSIONS: Pipeline Shield stents demonstrated superior complete occlusion rates (OKM D) at both the 6-month and the 1-year follow-up assessments compared with nonmodified surface FDSs. No significant differences were found in the safety profiles between the 2 types of stents with regard to thromboembolic complications and ischemic events. Further research with larger study populations is necessary to validate these findings.

Study of pH and Thermodynamic Parameters via Circular Dichroism Spectroscopy of a Recombinant Human Lactoferrin.

The production of human recombinant proteins to be used for therapeutic or nutritional purposes must focus on obtaining a molecule that is as close as possible to the native human protein. This biotechnological tool has been documented in various studies published in recent decades, with lactoferrin being one of those that has generated the most interest, being a promising option for recombinant technology. However, stability studies including thermodynamic parameters have not been reported for recombinant lactoferrin (Lf). The objective of this work was to obtain the human recombinant protein using the yeast Komagataella phaffii to study structural changes modifying pH and temperature using circular dichroism spectroscopy (CD). Thermodynamic parameters such as ΔH, ΔS and Tm were calculated and compared with commercial human lactoferrin. We propose the potential use of CD and thermodynamic parameters as a criterion in the production of recombinant proteins to be used in the production of specialized recombinant proteins.

Two-Year Myopia Management Efficacy of Extended Depth of Focus Soft Contact Lenses (MYLO) in Caucasian Children.

PURPOSE: To evaluate the progression of myopia as assessed by change in axial length (AL) and spherical equivalent (SE) from baseline in Caucasian children wearing extended depth of focus soft contact lenses (CLs) compared to distance single-vision spectacles. DESIGN: Prospective non-randomized comparative clinical trial. METHODS: A total of 90 children (6-13 years of age) with SE ranging from -0.75 to -10.00 diopters (D) were recruited. Of these children, 45 were fitted with CLs (MYLO, mark´ennovy), whereas 45 children wore spectacles. Cycloplegic refraction was measured with an auto-refractometer (Topcon-TRK-2P) and AL with an IOLMaster-700 (Zeiss) at 6-month intervals. Subjective responses after 1 month of CL wear related to vision and comfort were determined using a questionnaire with a scale from 1 (very poor) to 10 (excellent). High-contrast visual acuity (HCVA) and contrast sensitivity (CS) were evaluated at baseline, 12, and 24 months. RESULTS: After 2 years, mean change in SE/AL in the CL group was -0.62 ± 0.30 D/0.37 ± 0.04 mm and -1.13 ± 0.20 D/0.66 ± 0.03 mm in the spectacles group (P < .001). Cumulative absolute reduction in axial elongation (CARE) was 0.29 ± 0.06 mm. Difference in SE change was -0.50 ± 0.34 D. Although 100% of CL group had an AL increase ≤0.50 mm, all participants increased ≥0.50 mm in the spectacles group. In all, 53% of the CL group and 1% in the spectacles group showed a progression in SE ≤ -0.50D. All questionnaire items showed a mean value ≥9. There was a reduction logMAR HCVA in the CL compared to the spectacles group but it was less than 1 line (P < .001). CONCLUSIONS: Use of MYLO CLs reduced axial elongation and myopia progression compared to use of distance single-vision spectacles.

Design and evaluation of a mobile-based intervention for Maya adults during the COVID-19 pandemic

Introduction: The COVID-19 pandemic has had a direct impact on mental health. Inter national organisations have emphasised the vulnerability of indigenous people. Digital Mental Health approaches deliver online therapy as an evidence-based, effective, and accessible treat ment option for common mental health problems. However, the evidence regarding these ap proaches is limited in indigenous populations. The objective of this study is to describe the design, development, and evaluation of the efficacy of a self-applied online intervention regarding the psychological symptoms of depression, anxiety, and fear of COVID-19 in a sample of the Maya population. Method: A prospective longitudinal quantitative study was designed, where a single group was measured before and after receiving the online intervention. This study took place from April to September 2021 and consisted of six sessions delivered via WhatsApp in Spanish and Mayan. Results: The initial assessment was implemented with 82 participants who were evaluated using the Patient Health Questionnaire, Scale for Generalised Anxiety Disorder and the Fear of COVID-19 Scale; 18 participants remained in the intervention for the post-as sessment. Statistical differences were observed in PRE and POST measures of depression and anxiety, but not in fear of COVID-19. Conclusions: This study produced positive results for the first online mental health intervention implemented in the Latin American indigenous pop ulation. Future studies might consider developing similar interventions for other indigenous communities in Latin America.

Introducción: La pandemia de COVID-19 tuvo impacto directo en la salud mental. Organizaciones internacionales han enfatizado la vulnerabilidad de los pueblos indígenas. Los enfoques de salud mental digital brindan terapia en línea como una opción de tratamiento basada en evidencia, efectiva y accesible; sin embargo, los datos son limitados en población indígena. El objetivo de este estudio fue describir el diseño, desarrollo y evaluación de la eficacia de una intervención en línea autoaplicada sobre síntomas psicológicos de depresión, ansiedad y miedo al COVID-19 en una muestra de población maya. Método: Se diseñó un es tudio cuantitativo longitudinal prospectivo, donde se midió a un solo grupo antes y después de recibir la intervención en línea, implementada de abril a septiembre de 2021, que constó de seis sesiones impartidas vía WhatsApp, en español y maya. Resultados: La evaluación inicial se implementó con 82 participantes que fueron evaluados mediante el Cuestionario de Salud del Paciente, Escala para el Trastorno de Ansiedad Generalizada y Escala de Miedo al COVID-19; 18 participantes permanecieron para la evaluación posterior. Se observaron di ferencias estadísticas en las medidas pre- y post- de depresión y ansiedad, pero no miedo al COVID-19. Conclusiones: Este estudio arrojó resultados positivos de la primera intervención de salud mental en línea implementada en la población indígena latinoamericana. Estudios futuros podrían considerar el desarrollo de intervenciones similares para otras comunidades indígenas en América Latina.

Reliability and validity of proxy reports of impulsivity and aggression: An evidence-based assessment approach to psychological autopsy methods.

INTRODUCTION: Psychological autopsy methods often include measures of impulsivity and aggression. The aim is to assess their reliability and validity in a Spanish sample. METHODS: Cross-sectional web-based survey was fulfilled by 184 proband and proxy pairs. Data was collected on sociodemographic characteristics, impulsivity through Barratt Impulsiveness Scale (BIS-11), aggression through Buss-Perry Aggression Questionnaire (BPAQ), and history of suicide ideation. Proxies filled out BIS-11, BPAQ and suicide ideation with the responses they would expect from the probands. Reliability was assessed using intraclass correlation coefficients (ICC) between proband and proxies. Logistic regression analysis was performed to assess the predictive validity of proxy reports in predicting probands' suicide ideation. RESULTS: Bivariate analysis showed differences in BPAQ (Median 68 vs. 62; p=0.001), but not in BIS-11 (p>.050). BIS-11 showed good concordance (ICC=0.754; CI 95% 0.671-0.816) and BPAQ acceptable (ICC=0.592; CI 95% 0.442-0.699). In the probands regression model BPAQ predicted suicide ideation (OR 1.038; CI 95% 1.016-1.061) but not BIS-11 (OR 0.991; CI 95% 0.958-1.025). In the proxy-report model BPAQ also predicted probands' suicide ideation (OR 1.036; CI 95% 1.014-1.058) but not BIS-11 (OR 0.973; CI 95% 0.942-1.004). CONCLUSION: Used as proxy-reported assessment tools, BIS-11 showed better reliability than the BPAQ. However, both showed validity in Spanish population and could be included in psychological autopsy protocols.

A DRP-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial inner membrane-localized MICOS complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS complexes to promote normal mitochondrial morphology and respiratory function. Bioinformatic analyses reveal that Mmc1 is a distant relative of the Dynamin-Related Protein (DRP) family of GTPases, which are well established to shape and remodel membranes. We find that, like DRPs, Mmc1 self-associates and forms high molecular weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting it does not dynamically remodel membranes. These data are consistent with a model in which Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.

Development of a national proficiency test for SARS-CoV-2 detection by PCR in Colombia.

Background: Proficiency testing (PT) is a tool for ensuring the validity of results of testing laboratories and is essential when laboratories are working with assays authorised for emergency use or implementing novel techniques for detecting emerging pathogens. Methods: In collaboration with the National Health Institute of Colombia and with international support, we developed a qualitative PT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR). A proficiency test item (PTI) based on reference material (research grade) produced by the National Institute of Standards and Technologies (NIST) was prepared and characterised using three positive samples with varying concentrations of SARS-CoV-2 ribonucleic acid (RNA) and two negative (control) samples. Tests were distributed to 121 laboratories across the national network of public health laboratories in Colombia. Results: Positive samples had varying concentrations of SARS-CoV-2 RNA and were quantified by digital PCR (RT-ddPCR) assays for the E gene of SARS-CoV-2. We tested the ability of laboratories to detect low and high levels of viral RNA using samples with SARS-CoV-2 RNA concentrations of 1417 ± 216, 146 ± 28, and 14 ± 10 copies /uL (expanded uncertainty, k = 2, 95% confidence level) We also performed a semiquantitative analysis of instrumental responses (Ct values) reported by participating laboratories and homogeneity, stability, and characterisation studies of the produced materials to determine the adequacy of these materials and methods for use in the qualitative PT scheme. The PT evaluated reports for individual target genes from each laboratory; 98.3% of laboratories had satisfactory performance and the remaining 1.7% of laboratories had unsatisfactory performance for the detection of at least one of the reported genes. Conclusions: This PT scheme identified the potential metrological weaknesses of laboratories in the detection of SARS-CoV-2 by RT-PCR and may facilitate improvements in the quality of measurements from the perspective of public health surveillance.

Agreement and Reproducibility of Anterior Chamber Angle Measurements between CASIA2 Built-In Software and Human Graders.

PURPOSE: This study evaluated the agreement and reproducibility of ACA measurements obtained using the built-in software of the CASIA2 (Version 3G.1) and the measurements derived from expert clinicians. METHODS: Healthy volunteers underwent ophthalmological evaluation and AS-OCT examination. ACA measurements derived from automated and manual SS location were obtained using the CASIA2 automated software and clinician identification, respectively. The intraobserver, interobserver reproducibility, CASIA2-human grader reproducibility and CASIA2 repeatability were assessed using intraclass correlation coefficients (ICCs). RESULTS: The study examined 58 eyes of 30 participants. The CASIA2 software showed excellent repeatability for all ACA parameters (ICC > 0.84). Intraobserver, interobserver, and CASIA2-human grader reproducibility were also excellent (ICC > 0.87). Interobserver agreement was high, except for nasal TISA500, differing between observers 1 and 2 (p < 0.05). The agreement between CASIA2 measurements and human graders was high, except for nasal TISA500, where observer 1 values were smaller (p < 0.05). CONCLUSION: The CASIA2 built-in software reliably measures ACA parameters in healthy individuals, demonstrating high consistency. Although a small difference was observed in nasal TISA500 measurements, interobserver and CASIA2-human grader reproducibility remained excellent. Automated SS detection has the potential to facilitate evaluation and monitoring of primary angle closure disease.