Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants.

The ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology, and variant interpretation. This VCEP made specifications for the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines for the ataxia telangiectasia mutated (ATM) gene according to the ClinGen protocol. These gene-specific rules for ATM were modified from the ACMG/AMP guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar, and re-evaluation with the VCEP's ATM-specific rules resulted in four that were classified as benign, one as likely pathogenic, and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 of the 33 pilot variants were not VUS, leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM.

Expert panel consensus recommendations on the utilization of nebulized budesonide for managing asthma and COPD in both stable and exacerbation stages in Thailand.

OBJECTIVE: This study investigated the utilization of nebulized budesonide for acute asthma and COPD exacerbations as well as for maintenance therapy in adults. DATA SOURCES: We conducted a search on PubMed for nebulized budesonide treatment. SELECTED STUDIES: Selecting all English-language papers that utilize Mesh phrases "asthma," "COPD," "budesonide," "nebulized," "adult," "exacerbation," and "maintenance" without temporal restrictions, and narrowing down to clinical research such as RCTs, observational studies, and real-world studies. RESULTS: Analysis of 25 studies was conducted to assess the effectiveness of nebulized budesonide in asthma (n = 10) and COPD (n = 15). The panel in Thailand recommended incorporating nebulized budesonide as an additional or alternative treatment option to the standard of care and systemic corticosteroids (SCS) based on the findings. CONCLUSION: Nebulized budesonide is effective and well-tolerated in treating asthma and COPD, with less systemic adverse effects compared to systemic corticosteroids. High-dose nebulized budesonide can enhance clinical outcomes for severe and mild exacerbations with slow systemic corticosteroid response. Nebulized budesonide can substitute systemic corticosteroids in some situations.

A single-institution retrospective study of comprehensive genomic profiling tests based on C-CAT findings for advanced solid cancers.

BACKGROUND: In recent years, as the availability of precision therapies expands, there is increasing reliance on genomic profiling assays to help identify the most appropriate treatment options for patients with advanced cancers. We retrospectively investigated the results of comprehensive genomic profiling tests from the time insurance coverage began until recently and examined the status of genetic analysis. METHODS: We retrospectively reviewed the analysis results of 300 patients with advanced solid tumors who consented to comprehensive genomic profiling tests from October 2019 to December 2022. RESULTS: Of the 300 patients who underwent comprehensive genomic profiling tests, analysis results for 274 patients were obtained, and were reviewed by the Clinical Genome Expert Panel. Six specimens (2%) were discontinued due to patient deaths and deteriorations in general condition. The three most frequently occurring actionable genomic alterations observed were TP53 (47.4%), KRAS (28.1%) and CDKN2A (20.4%). The most common druggable variant was CDKN2A, which was noted in 52 (19%) of 274 patients. The next most common were PIK3CA, BRAF, KRAS and PTEN. The cancer types that showed a greater median number of actionable alterations comprised thyroid cancer, pancreatic cancer and colorectal cancer. CONCLUSIONS: In conclusion, comprehensive genomic profiling tests have the potential to be valuable in identifying genomic abnormalities. Even if there is no effective treatment at present, it may lead to a treatment in the future. Comprehensive genomic profiling tests should be considered for any cancer.

Guideline for the diagnosis and treatment of incomplete Kawasaki disease in children in China.

BACKGROUND: Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. METHODS: The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. RESULTS: These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. CONCLUSIONS: To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.

Derivation of no significant risk levels for three lower acrylates: Conclusions and recommendations from an expert panel.

A panel of toxicology, mode of action (MOA), and cancer risk assessment experts was engaged to derive no-significant-risk-levels (NSRLs) for three lower acrylates: methyl acrylate (MA), ethyl acrylate (EA), and 2-ethylhexyl acrylate (2EHA) using the best available science, data, and methods. The review was structured as a five-round, modified Delphi format, a systematic process for collecting independent and deliberative input from panel members, and it included several procedural elements to reduce potential sources of bias and groupthink. Input from the panel for key decisions in the dose-response assessments resulted in NSRL values of 530 µg/day (330-800 µg/day), 640 µg/day (280-670 µg/day), and 1700 µg/day (1300-2700 µg/day) for MA, EA, and 2EHA, respectively. Novel to this approach were the use of nonneoplastic lesions reported at point of contact where tumors have been reported in laboratory rodents, along with nonlinear extrapolation to low doses (uncertainty factor approach) based upon panel recommendations. Confidence in these values is considered medium to high for exposures applied to the routes of exposure tested (inhalation for MA and EA, dermal for 2EHA), but confidence is considered lower when applied to other routes of exposure.

Experts' perceptions on motivators and barriers of healthy and sustainable dietary behaviors among adolescents: The SWITCH project.

The interplay of influences shaping dietary behaviors of adolescents needs to be well-understood to develop effective strategies stimulating healthy and sustainable behaviors. This study aimed to identify the most relevant, urgent, changeable and effective motivators and barriers of healthy and sustainable dietary behaviors among adolescents (10-19 years), as perceived by an inter- and transdisciplinary expert panel. Experts working in practice (N = 19) and academia (N = 13) - in the field of sustainability, health, nutrition and/or education - participated in this exploratory mixed-methods study. Five online semi-structured focus groups were conducted (6-7 participants). Data was thematically analyzed by two coders independently, using the socioecological framework. Subsequently, the same experts individually selected the five most relevant determinants and rated those on their urgency, changeability and effectiveness through an online questionnaire (N = 21). Participants revealed a wide system of 31 main determinants including 173 sub-determinants that motivate or hinder healthy and sustainable eating among adolescents. This system of determinants was mapped on the different layers of the socioecological model: individual factors (25 motivators; 30 barriers), social environments (15 motivators; 13 barriers), physical environments (18 motivators; 15 barriers), macro-level environments (19 motivators; 38 barriers). 'Role of peers' (social environment) was selected most as a determinant to be targeted in interventions (N = 13; urgency (M = 6.38) changeability (M = 3.85), effectiveness (M = 5.62)), followed by 'food environment around school' (N = 9; urgency (M = 5.78) changeability (M = 3.44), effectiveness (M = 5.44)), 'social influences' (N = 7; urgency (M = 5.43) changeability (M = 4.00), effectiveness (M = 5.71)), 'autonomy in development' (N = 7; urgency (M = 6.00) changeability (M = 4.29), effectiveness (M = 5.86)) and 'food availability' (N = 7; urgency (M = 6.29) changeability (M = 3.29), effectiveness (M = 6.29)). The prioritized determinants indicate that adolescents should be provided more supportive social and physical environments that promote healthy and sustainable dietary behaviors, taking into account their growing autonomy.

Sodium Dehydroacetate and Dehydroacetic Acid.

The Expert Panel for Cosmetic Ingredient Safety (Panel) first published a safety assessment of Sodium Dehydroacetate and Dehydroacetic Acid in 1985. The Panel previously concluded that Sodium Dehydroacetate and Dehydroacetic Acid are safe as used in the present practices of use and concentration, as stated in that report. Upon re-review in 2003, the Panel reaffirmed the original conclusion, as published in 2006. The Panel reviewed updated frequency and concentration of use data again in 2023, in addition to any newly available, relevant safety data. Considering this information, as well as the information provided in the original safety assessment and the prior re-review document, the Panel reaffirmed the 1985 conclusion.

Safety Assessment of Polysilicone-11 as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Polysilicone-11 as used in cosmetic formulations. This ingredient is reported to function as a film former. The Panel considered the available data and concluded that Polysilicone-11 is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Hydrogen Peroxide as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Hydrogen Peroxide for use in cosmetics. This ingredient is reported to function in cosmetics as an antimicrobial agent, cosmetic biocide, oral health care agent, and oxidizing agent. The Panel reviewed the data relevant to the safety of this ingredient and concluded that Hydrogen Peroxide is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Triphenyl Phosphate as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Triphenyl Phosphate, which is reported to function as a plasticizer in manicuring products. The Panel reviewed the available data to determine the safety of this ingredient. The Panel concluded that Triphenyl Phosphate is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Zinc Phenolsulfonate.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1986 and a previous re-review in 2004, along with updated information regarding product types and concentrations of use. Considering this information, the Panel confirmed that Zinc Phenolsulfonate is safe as a cosmetic ingredient in the present practices of use and concentration as described in this report.

Safety Assessment of Capryloyl Salicylic Acid as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of Capryloyl Salicylic Acid in cosmetic products; this ingredient is reported to function as a skin conditioning agent. The Panel reviewed relevant data relating to the safety of this ingredient in cosmetic formulations, and concluded that the available data are insufficient to make a determination that Capryloyl Salicylic Acid is safe under the intended conditions of use in cosmetic formulations.

Safety Assessment of Hydroxyethyl Urea as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Hydroxyethyl Urea, which is reported to function as a humectant and a hair and skin conditioning agent. The Panel reviewed the available data to determine the safety of this ingredient. The Panel concluded that Hydroxyethyl Urea is safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating.

Safety Assessment of Basic Red 76 as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Basic Red 76, which is reported to function in cosmetics as a hair colorant and hair-conditioning agent. The Panel reviewed the available data to determine the safety of this ingredient. The Panel concluded that Basic Red 76 is safe for use as a hair dye ingredient in the present practices of use and concentration described in the safety assessment.

Safety Assessment of Methylxanthines as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of three methylxanthines, Caffeine, Theobromine, and Theophylline, as used in cosmetics. All of these ingredients are reported to function as skin-conditioning agents in cosmetic products. The Panel reviewed the data relevant to the safety of these ingredients and concluded that Caffeine, Theobromine, and Theophylline are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Isobutane, Isopentane, Butane, and Propane.

The Expert Panel for Cosmetic Ingredient Safety (Panel) first published the Final Report of the safety of Isobutane, Isopentane, Butane, and Propane in 1982. The Panel previously concluded that these ingredients are considered safe as cosmetic ingredients under the present conditions of concentration and use, as described in that safety assessment. Upon re-review in 2002, the Panel reaffirmed the original conclusion, as published in 2005. The Panel reviewed update frequency and concentration of use data again in 2023, in addition to newly available, relevant safety data. Considering this information, as well as the information provided in the original safety assessment and the prior re-review document, the Panel reaffirmed the 1982 conclusion for Isobutane, Isopentane, Butane, and Propane.

Laneth Acetates.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982 and a previous re-review in 2002, along with updated information regarding product types and concentrations of use. Considering this information, the Panel confirmed that Laneth-9 Acetate and Laneth-10 Acetate are safe for topical application to humans in the present practices of use and concentration as described in this report.

Safety Assessment of Alkanoyl Lactyl Lactate Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 alkanoyl lactyl lactate salts. These ingredients have the surfactant function in cosmetics in common. The Panel reviewed data relevant to the safety of these ingredients, and concluded that these 10 ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment (QRA) or other accepted methodologies.

Safety Assessment of Polyol Phosphates as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 polyol phosphates. Some of the possible functions in cosmetics that are reported for this ingredient group are chelating agents, oral care agents, and skin conditioning agents. The Panel reviewed relevant data relating to the safety of these ingredients under the intended conditions of use in cosmetic formulations, and concluded that Sodium Phytate, Phytic Acid, Phytin, and Trisodium Inositol Triphosphate are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the data are insufficient to determine the safety of the following 6 ingredients as used in cosmetics: Disodium Glucose Phosphate, Manganese Fructose Diphosphate, Sodium Mannose Phosphate, Trisodium Fructose Diphosphate, Xylityl Phosphate, and Zinc Fructose Diphosphate.

Safety Assessment of Palm-Derived Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 8 palm tree (Euterpe edulis (juçara) and Euterpe oleracea (açaí))-derived ingredients as used in cosmetic products; these ingredients are reported to function mostly as skin conditioning agents. The Panel reviewed relevant data relating to the safety of these ingredients in cosmetic formulations. Industry should continue to use good manufacturing practices to limit impurities. The Panel concluded that palm tree (açaí and juçara)-derived ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment.