Testing Guidelines Research Articles

HER2 evaluation for clinical decision making in human solid tumours: pearls and pitfalls.

The significant clinical benefits of human epidermal growth factor receptor 2 (HER2)-targeted therapeutic agents have revolutionized the clinical treatment landscape in a variety of human solid tumours. Accordingly, accurate evaluation of HER2 status in these different tumour types is critical for clinical decision making to select appropriate patients who may benefit from life-saving HER2-targeted therapies. HER2 biomarker scoring criteria is different in different organ systems, and close adherence to the corresponding HER2 biomarker testing guidelines and their updates, if available, is essential for accurate evaluation. In addition, knowing the unusual patterns of HER2 expression is also important to avoid inaccurate evaluation. In this review, we discuss the key considerations when evaluating HER2 status in solid tumours for clinical decision making, including tissue handling and preparation for HER2 biomarker testing, as well as pathologist's readout of HER2 testing results in breast carcinomas, gastroesophageal adenocarcinomas, colorectal adenocarcinomas, gynaecologic carcinomas, and non-small cell lung carcinomas.

Within-laboratory reproducibility of Ames test results: Are repeat tests necessary?

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross-sector working group examined the within-laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals. This study focused primarily on NTP tests conducted using the standard Organization for Economic Co-operation and Development Test Guideline 471 preincubation test protocol with 10% rat liver S9 for metabolic activation, although 30% rat S9 and 10 and 30% hamster liver S9 were also evaluated. The reproducibility of initial negative responses in all strains with and without 10% S9, was quite high, ranging from 95% to 99% with few exceptions. The within-laboratory reproducibility of initial positive responses for strains TA98 and TA100 with and without 10% rat liver S9 was ≥90%. Similar results were seen with hamster S9. As expected, the reproducibility of initial equivocal responses was lower, <50%. These results will provide context for determining the optimal design of recommended test protocols for use in screening both individual chemicals and complex mixtures, including botanicals.

Use of Lentivirus-Based Method for Establishing TK6 Human Cell Lines Expressing Cytochrome P450 and its Applications in Genotoxicity Testing.

The human lymphoblastoid cell line TK6 stands out as the most widely employed human cell line in genotoxicity testing, as recommended by various testing guidelines for in vitro assessments. Nevertheless, like many testing cell lines, TK6 lacks functional phase I drug-metabolizing enzymes crucial for chemical genotoxicity evaluations. This protocol introduces a lentivirus-based methodology for establishing a panel of TK6-derived cell lines, each expressing one of 14 cytochrome P450s (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7). The utilization of a lentiviral expression system ensures stable transduction, offering notable advantages such as sustained transgene expression, high transduction efficiency, positive selection feasibility, and user-friendly application. Additionally, we present a detailed procedure for validating the enhanced expression of each CYP in the established cell lines through real-time PCR, western blotting, and mass spectrometry analysis. Lastly, we exemplify the application of these CYP-expressing TK6 cell lines in genotoxicity testing, employing a flow-cytometry-based in vitro micronucleus test. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Lentivirus production and transduction for TK6 cells Support Protocol: Selecting a single clone of CYP-expressing TK6 cells Basic Protocol 2: Validation of CYP expression in TK6 cell lines Basic Protocol 3: Application of transduced cell lines in flow-cytometry-based micronucleus assay.

Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats

Annona muricata fruit (i.e. Soursoup or custard apple a tropical plant species known for its edible fruit)has been attributed with numerous medicinal benefits (including antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, anxiolytic, anti-stress, anti-ulcerogenic, wound healing, hepato-protective, anti-icteric, hepatoprotective, anticancer and antihyperglycemic activities) as well as some toxicological effects (neurotoxicity and neurodegeneration). Despite its ancestral use and wide applications in human health, scientific information on its oral safety remains scanty. In this study, the oral safety of 100 mg/kd/day, 200 mg/kg/day and 400 mg/kg/day of the aqueous fruit extract of Annona Muricata (AFAM) was evaluated in young adult, male and female white albino Wistar rats using standard acute and 42-days sub-chronic oral toxicity testing guidelines on anthropometric, biochemical, hematological and histo-pathological endpoints. In addition, preliminary qualitative and quantitative analyses of AFAM were undertaken using standard procedures. Results of the study showed that the estimated LD50 value for the acute oral toxicity study of AFAM calculated to be greater than 5 g/kg body weight/oral route although the testing was associated with transient but reversible behavioral toxicities. For its sub-chronic oral toxicity testing, AFAM treatment resulted in profound %weight gain, decreases in the serum triglycerides and very low density lipoprotein cholesterol and liver enzymes. Similarly, prolonged oral AFAM treatments caused significant decrease and increase in the differential neutrophils and platelet counts, respectively while the hist-opathological features of hepatic steatos is and renal tubule collapse in the AFAM-treated livers and kidneys, respectively suggested possible increased intrahepatic lipids biosynthesis and nephrotoxicity. The preliminary phytochemical analyses of AFAM showed the presence and relative amount of flavonoids, alkaloids, tannin, glycosides, saponin, and reducing sugars while the Gas Chromatography-Mass spectroscopy showed the relative abundance of thirteen compounds. Composite analyses conducted on the extract showed the presence of carbohydrate (64.65%), protein (2.14%), moisture content (8.07%), ash value (6.73%), lipid (14.22%) and fiber (4.19%). Overall, the study suggested that the prolonged AFAM oral treatments could predispose to the development of fatty liver disease from de novo intrahepatic biosynthesis of triglycerides, nephrotoxicity and hematotoxicity. In conclusion, the results of this study showed that prolonged consumption of AFAM should be with a great caution as it could pose serious health concerns.

Determination of amphotericin B antifungal susceptibility in Candida strains using an inverted microscope.

Invasive Candida infections have recently shown a significant increase in prevalence and are associated with high mortality rates. Initiating early antifungal treatment in patients with candidemia is vital. The aim of our study was to compare the antifungal susceptibility results of a new method called Flat Plate Method modified from reference "Clinical and Laboratory Standards Institute (CLSI) microdilution method by us with Sensitititre Yeast One colorimetric method and the reference CLSI method. We tested 100 Candida isolates from blood cultures. We followed the CLSI M27-A3 (reference method for broth dilution antifungal susceptibility testing of yeasts; third edition) guidelines for testing in vitro susceptibility to amphotericin B. In the Flat Plate method, 96-well plates were used for evaluation with an inverted microscope. Minimum inhibitory concentration (MIC) values in the SYO method were measured following the manufacturer's instructions. The MIC values obtained by all three methods were considered compatible if they were within ± 2 dilution limits. The SYO method detected C. albicans and C. glabrata with 100% essential agreement, whereas there was 96.29% essential agreement in the case of C. parapsilosis. In the Flat Plate method, the essential agreement with amphotericin B was 91.42%, for C. albicans isolates and 89.47%.for C. glabrata strains. When determining early antifungal susceptibility using the Flat Plate method, the results are obtained quickly, with high accuracy, and without incurring additional costs. However, there is a need for comprehensive studies comparing different antifungals.

Designing Academic Data Visualization Dashboard Using Google Data Studio at SMPN 8 Pariaman

This study aims to use Google Data Studio to produce an academic data visualization dashboard system to display information, which can manage academic data, namely teacher attendance data and student grades, to provide decision-making support for decision makers in the monitoring process and evaluate school internal processes and monitor student grades at SMPN 8 Pariaman School. The type of research used is the R&amp;D (Research and Development) approach SDLC (Systems Development Life Cycle) method with a prototype model. The stages carried out are communication, planning, modeling, construction and handover (handover). The system testing method studied uses questionnaire guidelines for functional testing to test system functionality to verifiers and usability testing to test system usability and suitability of functions and services to users. Based on the results of the validator functional test study, the results of meeting the functional requirements with both a value of 1 and 89% of the feasibility value of the system usability test are classified as very feasible. Therefore, it can be concluded that the academic data visualization dashboard system using Google Data Studio meets the requirements and is very suitable as a support for SMPN 8 Pariaman School in processing academic data on teacher attendance and student grades.

Advancing Endocrine Disruptors via In Vitro Evaluation: Recognizing the Significance of the Organization for Economic Co-Operation and Development and United States Environmental Protection Agency Guidelines, Embracing New Assessment Methods, and the Urgent Need for a Comprehensive Battery of Tests.

Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition of their impact on human health and the environment has stimulated attention and research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, and industry representatives, are collaborating to develop robust methodologies and guidelines for assessing these disruptors. A key aspect of these efforts is the development of standardized testing protocols and guidelines that aim to provide consistent and reliable methods for identifying and characterizing endocrine disruptors. When evaluating the potential endocrine-disrupting activity of chemicals, no single test is capable of detecting all relevant endocrine-disrupting agents. The test battery approach is designed to reduce the risk of false negative results for compounds with toxic potential. A weight-of-evidence approach is therefore necessary for endocrine disruptor evaluation. This approach considers various types of data from multiple sources, assessing the overall strength, consistency, and reliability of the evidence. OECD guidelines are highly regarded for their scientific rigor, transparency, and consensus-based development process. It is crucial to explore and develop new methodologies that can effectively evaluate the risks associated with potential endocrine disruptors. Integrating these methods into a comprehensive weight-of-evidence framework will enhance risk assessments and facilitate informed decisions regarding the regulation and management of these substances, ensuring the protection of human health and the environment from their adverse effects.

Use of in vitro methods combined with in silico analysis to identify potential skin sensitizers in the Tox21 10K compound library.

Introduction: Skin sensitization, which leads to allergic contact dermatitis, is a key toxicological endpoint with high occupational and consumer prevalence. This study optimized several in vitro assays listed in OECD skin sensitization test guidelines for use on a quantitative high-throughput screening (qHTS) platform and performed in silico model predictions to assess the skin sensitization potential of prioritized compounds from the Tox21 10K compound library. Methods: First, we screened the entire Tox21 10K compound library using a qHTS KeratinoSensTM (KS) assay and built a quantitative structure-activity relationship (QSAR) model based on the KS results. From the qHTS KS screening results, we prioritized 288 compounds to cover a wide range of structural chemotypes and tested them in the solid phase extraction-tandem mass spectrometry (SPE-MS/MS) direct peptide reactivity assay (DPRA), IL-8 homogeneous time-resolved fluorescence (HTRF) assay, CD86 and CD54 surface expression in THP1 cells, and predicted in silico sensitization potential using the OECD QSAR Toolbox (v4.5). Results: Interpreting tiered qHTS datasets using a defined approach showed the effectiveness and efficiency of in vitro methods. We selected structural chemotypes to present this diverse chemical collection and to explore previously unidentified structural contributions to sensitization potential. Discussion: Here, we provide a skin sensitization dataset of unprecedented size, along with associated tools, and analysis designed to support chemical assessments.

Seismic tension testing of cast-in specialty inserts under different cyclic loading protocols

The seismic performance of an anchor is primarily evaluated through cyclic loading tests following current qualification testing guidelines such as ACI 355.2 and ETAG 001 Annex E. However, recent reports suggest that these guidelines are insufficient in assessing the ultimate performance of anchors, particularly in the post-peak region. Hence, additional qualification tests are required to supplement these guidelines. Although the testing protocol of FEMA 461 could be considered a promising alternative, there is currently no concrete research related to its application. Herein, we performed cyclic tension loading tests on recently developed headed cast-in specialty inserts using both the existing anchor qualification testing guidelines and the FEMA 461 protocol and compared their behavior in terms of strength, displacement, stiffness, and strain. The new insert anchors exhibited only negligible differences in their performance, depending on the applied loading protocols. We also discuss a more efficient cyclic loading method for evaluating the seismic performance of the anchors and subsequently propose the application of the FEMA 461 testing protocol for anchor qualification tests.

Machine learning-based identification of colorectal advanced adenoma using clinical and laboratory data: a phase I exploratory study in accordance with updated World Endoscopy Organization guidelines for noninvasive colorectal cancer screening tests.

The recent World Endoscopy Organization (WEO) guidelines now recognize precursor lesions of colorectal cancer (CRC) as legitimate screening targets. However, an optimal screening method for detecting advanced adenoma (AA), a significant precursor lesion, remains elusive. We employed five machine learning methods, using clinical and laboratory data, to develop and validate a diagnostic model for identifying patients with AA (569 AAs vs. 3228 controls with normal colonoscopy). The best-performing model was selected based on sensitivity and specificity assessments. Its performance in recognizing adenoma-carcinoma sequence was evaluated in line with guidelines, and adjustable thresholds were established. For comparison, the Fecal Occult Blood Test (FOBT) was also selected. The XGBoost model demonstrated superior performance in identifying AA, with a sensitivity of 70.8% and a specificity of 83.4%. It successfully detected 42.7% of non-advanced adenoma (NAA) and 80.1% of CRC. The model-transformed risk assessment scale provided diagnostic performance at different positivity thresholds. Compared to FOBT, the XGBoost model better identified AA and NAA, however, was less effective in CRC. The XGBoost model, compared to FOBT, offers improved accuracy in identifying AA patients. While it may not meet the recommendations of some organizations, it provides value for individuals who are unable to use FOBT for various reasons.

Genetic changes and testing associated with childhood glaucoma: A systematic review.

Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma.

In vivo alkaline comet assay: Statistical considerations on historical negative and positive control data

The alkaline comet assay is frequently used as in vivo follow-up test within different regulatory environments to characterize the DNA-damaging potential of different test items. The corresponding OECD Test guideline 489 highlights the importance of statistical analyses and historical control data (HCD) but does not provide detailed procedures. Therefore, the working group “Statistics” of the German-speaking Society for Environmental Mutation Research (GUM) collected HCD from five laboratories and >200 comet assay studies and performed several statistical analyses. Key results included that (I) observed large inter-laboratory effects argue against the use of absolute quality thresholds, (II) > 50% zero values on a slide are considered problematic, due to their influence on slide or animal summary statistics, (III) the type of summarizing measure for single-cell data (e.g., median, arithmetic and geometric mean) may lead to extreme differences in resulting animal tail intensities and study outcome in the HCD. These summarizing values increase the reliability of analysis results by better meeting statistical model assumptions, but at the cost of information loss. Furthermore, the relation between negative and positive control groups in the data set was always satisfactorily (or sufficiently) based on ratio, difference and quantile analyses.

The impact of supraventricular arrhythmias on the outcomes of guideline-compliant implantable cardioverter defibrillator programming.

Several implantable cardioverter defibrillators (ICD) programming strategies are applied to minimize ICD therapy, especially unnecessary therapies from supraventricular arrhythmias (SVA). However, it remains unknown whether these optimal programming recommendations only benefit those with SVAs or have any detrimental effects from delayed therapy on those without SVAs. This study aims to assess the impact of SVA on the outcomes of ICD programming based on 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines. Consecutive patients who underwent ICD insertion for primary prevention were classified into four groups based on SVA status and ICD programming: (1) guideline-concordant group (GC) with SVA, (2)GC without SVA, (3) nonguideline concordant group (NGC) with SVA, and (4)NGC without SVA. Cox proportional hazard models were analyzed for freedom from ICD therapies, shock, and mortality. Seven hundred and seventy-two patients (median age, 64 years) were enrolled. ICD therapies were the most frequent in NGC with SVA (24.0%), followed by NGC without SVA (19.9%), GC without SVA (11.6%), and GC with SVA (8.1%). Guideline concordant programming was associated with 68% ICD therapy reduction (HR 0.32, p = .007) and 67% ICD shock reduction (HR 0.33, p = .030) in SVA patients and 44% ICD therapy reduction in those without SVA (HR 0.56, p = .030). Programming ICDs in primary prevention patients based on current guidelines reduces therapy burden without increasing mortality in both SVA and non-SVA patients. A greater magnitude of reduced ICD therapy was found in those with supraventricular arrhythmias.

Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice

BackgroundCarbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo.ResultsMutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach.ConclusionsCarbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.

GiOPARK Project: The Genetic Study of Parkinson's Disease in the Croatian Population.

Parkinson's disease is a neurological disorder that affects motor function, autonomic functions, and cognitive abilities. It is likely that both genetic and environmental factors, along with age, contribute to the cause. However, there is no comprehensive guideline for genetic testing for Parkinson's disease, and more research is needed to understand genetic variations in different populations. There has been no research on the genetic background of Parkinson's disease in Croatia so far. Therefore, with the GiOPARK project, we aimed to investigate the genetic variants responsible for Parkinson's disease in 153 Croatian patients with early onset, familial onset, and sporadic late-onset using whole-exome sequencing, along with multiplex ligation-dependent probe amplification and Sanger sequencing in select patients. We found causative variants in 7.84% of the patients, with GBA being the most common gene (4.58%), followed by PRKN (1.96%), ITM2B (0.65%), and MAPT (0.65%). Moreover, variants of uncertain significance were identified in 26.14% of the patients. The causative variants were found in all three subgroups, indicating that genetic factors play a role in all the analyzed Parkinson's disease subtypes. This study emphasizes the need for more inclusive research and improved guidelines to better understand the genetic basis of Parkinson's disease and facilitate more effective clinical management.

Risk of Primary Incident Hepatitis C Infection Following Bacterial Sexually Transmissible Infections Among Gay and Bisexual Men in Australia From 2016 to 2020.

In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11-3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42-5.32]) and rectal gonorrhea (2.54 [1.28-5.05]) diagnoses were associated with incident HCV. Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP.

Investigation on the organocatalyzed ROP of δ-tetradecalactone: From polymerization to biodegradation

Searching for biobased and biodegradable polymers, we explored the organocatalytic ring-opening polymerization (ROP) of a renewable n-alkyl δ-lactone, namely δ-tetradecalactone (δ-TDL) that can be extracted from coconut oil, and we studied the ready biodegradability of the corresponding polyester. As reported for other n-alkyl δ-lactones, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was used to perform the bulk and room temperature ROP of δ-TDL. A study of the purification of the monomer prior to its ROP showed the importance of the combination of a distillation process and an elution through basic alumina to remove most of the impurities and obtain the higher molar masses. Despite this careful purification, capped molar masses were obtained (<40 kg/mol) and attributed by NMR and MALDI-ToF spectroscopy to TBD initiation and other side-initiators contained in the monomer, which were not possible to be identified. Other catalysts such as diphenyl phosphate (DPP) and the phosphazene superbase t-BuP4 combined with a thiourea were also tried. The assessment of poly(δ-tetradecalactone) (pTDL) ready biodegradability was finally performed using the OECD test guideline 301F and showed the obtention of up to 41 % biodegradation rate in 28 days using a bioavailability improvement method.

Defining and Grading an Obstructive Ventilatory Impairment: American Thoracic Society/ European Respiratory Society Interpretive Strategies of 2005 Versus 2022

Background: The American Thoracic Society (ATS) and the European Respiratory Society (ERS) have issued several updates to their guidelines for lung function testing between 2005 and 2022.&#x0D; Objective: We aimed to compare ATS/ERS recommendations for 2005(R1) and 2022(R2) in defining Obstructive Ventilatory Impairment (OVI) and in classifying its severity.&#x0D; Patients and Methods: It was a retrospective comparative study including 1129 patients. All patients underwent spirometry with measurement of Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC). An OVI was considered according to R1 when FEV1/FVC ratio is under the Lower Limit of Normal (LLN) and when the z-score of FEV1/FVC ratio is under -1.645 according to R2. For the severity levels of airflow obstruction: ATS/ERS previously recommended the use of percent predicted FEV1 with 5 levels using cut values of 70%, 60%, 50% and 35%. Recently updated for z-scores with cut values of -2, -2.5 and -4. Mean age was 54.23±19.23 years.&#x0D; Results: For defining an OVI, both definitions were comparable (529 patients with OVI). For the severity classification, the following proportions were assessed: 151 mild, 86 moderate,84 moderately severe, 133 severe and 75 very severe vs 148 mild, 238 moderate, 76 severe and 67 cases having a normal FEV1 (z-score of FEV1 above -1.645), which were classified as mild according to R1. Mild OVI(R2) were distributed according to R1 into 74 mild, 51 moderate, 16 moderately severe and 7 severe. Moderate OVI (R2) were dispatched using R1 to 10 mild, 34 moderate, 66 moderately severe, 103 severe and 25 very severe. Severe OVI(R2) were classified as 1 moderate, 2 moderately severe, 23 severe and 50 very severe.&#x0D; Conclusion: ATS/ERS new and previous recommendations seem to be comparable in defining OVI. However, discrepancies were assessed in classifying its severity.

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Comparative Analysis of Main Agronomic Traits of Different Pleurotus giganteus Germplasm Resources.

Agronomic traits are key components in variety protection, cultivar development, and the formulation of DUS (distinct, uniform, and stable) test guidelines. P. giganteus is an increasingly popular and commercially promising edible macrofungi. In this study, both mycelial performance and fruiting body characters of 15 Pleurotus giganteus strains were investigated. The temperature gradient culture test indicated that, although most of the strains achieved optimal mycelial growth between 24 and 28 °C, a statistical difference in mycelial growth rates and temperature adaptability among strains were found, supporting that this trait has the potential to be adopted as an indicator in distinguishing strains. In the fruiting performance tests, the coefficient of variation (CV) of tested traits ranged from 5.30% (pileus diameter) to 18.70% (individual mushroom weight). The mushroom yields ranged from 103.37 g/bag (strain No. 15) to 275.76 g/bag (strain No. 9). The large divergence observed in individual mushroom weight tested strains, ranging from 40.88 g to 78.39 g (with median between 37.69 and 79.395 g), make it highly selective and a potential indicator in variety development. Strain No. 9 had the advantages of forming larger, heavier fruiting bodies and a more obvious funnel shape, which also exhibited the highest biological efficiency (15.61%). The results suggested some morphological traits showed high variety difference, such as pileus diameter (55.75 mm to 66.48 mm), stipe length (92.59 mm to 177.51 mm), stipe diameter (16.14 mm to 23.52 mm), and pileus thickness (13.38 mm to 19.75 mm). In the cluster analysis, the tested strains were grouped into four clusters based on agronomic traits: cluster Ⅰ comprised six strains (No. 6, No. 11, No. 8, No. 1, No. 14, and No. 9) with high mushroom yield; cluster Ⅱ included four strains (No. 3, No. 10, No. 7, and No. 4) with large pileus diameter and short stipe; cluster ⅡI consisted of four strains (No. 5, No. 12, No. 13, and No. 15) with relatively lower yields; and cluster Ⅳ included only strain No. 2 which was low in yield, individual mushroom weight, and biological efficiency, accompanied by smaller pileus size and shorter stipe. The results of the correlation analysis indicated three traits, including individual mushroom weight, stipe length, and pileus weight, were positively associated with high yield. This study suggested P. giganteus germplasm resources are of high abundance and their agronomic diversity is useful in distinguishing and developing different varieties. The findings of this work provide knowledge on the agronomic traits and cultivation performance of various P. giganteus strains, laying a foundation for the development of its DUS test guidelines and variety protection, as well as providing reference for the breeding and phenotype selection of high-quality cultivars.