Adaptive designs in clinical trials: a systematic review-part I.

BACKGROUND: Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community. METHODS: Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein. RESULTS: Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials. CONCLUSION: This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. STUDY PROTOCOL REGISTRATION: https://doi.org/10.1186/s13063-018-2934-7 .

Variations in the Sensory Attributes of Infant Formula among Batches and Their Impact on Maternal Consumer Preferences: A Study Combining Consumer Preferences, Pivot Profile, and Quantitative Descriptive Analysis.

The sensory quality of infant formula (IF) has a significant impact on the preferences and purchasing behavior of maternal consumers. Consumer-based rapid descriptive methods have become popular and are widely preferred over classical methods, but the application of Pivot Profile (PP) in IF is still little explored. In this study, both Pivot Profile (PP) and Quantitative Descriptive Analysis (QDA) were applied to characterize the sensory profile of 12 batches of one-stage and three-stage IF with different storage periods, respectively, along with consumer preference data to determine the flavors contributing to liking. The results of PP and QDA aligned moderately well, with the most perceptible differences identified as "fishy", "milky", and "T-sweet" attributes. IFs with shorter storage times were highly associated with "milky" aromas and "T-sweet" tastes, whereas IFs with longer storage times exhibited a strong correlation with "fishy" and "oxidation" aromas. External preference analysis highlighted that the occurrence of "fishy" and "oxidation" aromas during prolonged storage periods significantly reduced the consumer preference for IFs. Conversely, the perception of "milky" and "creamy" aromas and "T-sweet" tastes may be critical positive factors influencing consumer preference. This study provided valuable insights and guidance for enhancing the sensory quality and consumer preference of IF.

Validation of Optimization Methods for Sensory Characteristics Using Rate-All-That-Apply and Intensity Scales: A Case Study of Apple Juice.

Preference mapping (PM), which integrates consumer and descriptive analysis (DA) data to identify attributes that drive consumer liking, is widely employed for product optimization. However, a limited group of trained panelists cannot fully represent the diverse consumer population or reliably predict market acceptance. Consequently, numerous studies have explored consumer-based methodologies as potential replacements for DA; however, their efficacy for product optimization remains limited. Therefore, this study was conducted to explore the potential of optimizing products using two consumer-based profiling techniques as alternatives to DA in external preference mapping (EPM). Overall, 8 trained panelists profiled 12 sensory attributes of 7 commercial apple juices, whereas 160 consumers assessed the same attributes using a 5-point rate-all-that-apply (RATA) scale and a 10 cm intensity scale (IS). Danzart's response surface ideal modeling was employed to identify optimal products using DA, RATA, and IS through barycenter calculations, focusing on three products from the original consumer test located around the group ideal point. Overall, the ideal products of the group and their sensory characteristics were successfully identified using DA, RATA, and IS. Regarding sensory intensities, high concordance was observed between DA and RATA (Rv = 0.92) and between DA and IS (Rv = 0.91). Overall liking and preference scores for products mixed at the optimal ratio for each method showed no significant differences in preference among the ideal products identified using DA, RATA, and IS. This study suggests that both RATA and IS are viable alternatives to DA in EPM for identifying ideal sensory profiles.

Relationship between consumer acceptance, sensory characteristics, and physicochemical characteristics of "Fuji" apples from different origins.

This study examines the acceptance of young Chinese consumers for different "Fuji" apples, focusing on their sensory characteristics and physicochemical foundations. The sensory attributes of the samples were evaluated using a combination of static descriptive analysis (DA) and temporal check-all-that-apply fading (TCATA-fading) methods. Furthermore, the volatile compounds, soluble sugars, organic acids, and textural parameters of the samples were analyzed. The findings revealed that participants favored apples that were perceived as "sweet," "crunchy," "juicy," and "aromatic." The results from the DA indicated that certain sensory attributes, such as "sweet," "vanilla," "honey," and "pear" positively influenced acceptance, while attributes like "sour," "hard," and "grass" had a negative impact. The findings from both the DA and TCATA-fading methods were consistent with each other. In terms of dynamic evaluation, sweetness, and sourness were the initial perceptions, followed by a range of other flavors. Notably, our data suggested that sweetness perception could be enhanced by attributes such as "honey" and "banana." Additionally, the sugar-acid ratio and specific volatile compounds, including hexanal, (E)-2-hexenal, ß-damascenone, butyl acetate, and propyl 2-methylbutyrate, were found to influence the perception of sweetness in apples. PRACTICAL APPLICATION: This study helps to understand the effect of different origins on the acceptance of "Fuji" apples and to know the sensory and material basis for the emergence of such differences. It is beneficial for growers and marketers to improve 'Fuji' apples.

Comparison of pre-fermentation and post-fermentations alcohol adjustments on aromatic chemistry and sensory composition of Sauvignon blanc wine.

Harvest and alcohol adjustment effects were evaluated for Sauvignon blanc grapes harvested at three potential alcohols (11, 13 and 15% (v/v)) by gas chromatography-mass spectrometry and descriptive analysis. Alcohol concentration was controlled for pre-fermentation by dilution or chaptalization and post-fermentation by dealcoholization. The initial experimental alcohol was treated as the control and the dealcoholized wine the treatment. Wine treatments sharing the same alcohol target and harvest date as the dealcoholized wine were designated as the negative control. All aroma compounds measured increased because of higher ethanol or declined because of dealcoholization. Similar aroma concentrations were observed to be a factor of alcohol concentration, apart from volatile thiols which were influenced by harvest. Statistical analysis of sensory and aroma compounds showed a corresponding relationship between low versus high alcohol wines. Dealcoholization appears to be an effective tool for altering wine aroma and winemaking style with comparable aroma loss to pre-fermentation adjustment.

Flavoromic analysis of wines using gas chromatography, mass spectrometry and sensory techniques.

Various sensory perceptions drive the quality and typicality of wines, with the volatile profile playing a fundamental role in the characteristics of odor, aroma and consequently flavor, which combines the smell (odor and aroma), taste, and trigeminal sensations. Efforts have been made in both the field of instrumental and sensory analysis to understand the relationship of volatile compounds with sensory attributes in omics approaches. Gas chromatography (monodimensional and two-dimensional (heartcutting and comprehensive)) associated with mass spectrometry (GC/MS, GC-GC/MS and GCxGC/MS) and chemometric tools have contributed to foodomics analyses, specifically those linked to metabolomics/volatilomics. These tools, along with the elucidation of sensory properties (sensomics), lead to advanced results in the field of flavoromics. They also help to define the best practices in both vineyard management and winemaking that enable the production of high-quality wines. The objective of this review is to report the challenges of determining the volatile profile of wines, pointing out the ways that can be followed in successful identification and quantification of volatile compounds. The state of the art of sensory evaluation methods is also addressed, providing information that helps in choosing the most appropriate sensory method to be conducted with chromatographic analysis to achieve more in-depth results in the field of flavoromics.

Chasing the chill: Unveiling the dynamic flavors and textures of ice cream formulations.

In this study, nine commercial ice creams and four prototypes were assessed. For the sensory analysis, quantitative descriptive analysis (QDA), and temporal dominance of sensations (TDS) methodology were used. According to the QDA results, full-composition ice cream showed significantly higher differences (p < .05) in terms such as vanilla and sweet flavors, brightness, creamy texture and appearance, and viscosity, exhibiting longer melting times. Functional ice creams showed significantly higher differences (p < .05) in terms like viscosity, creamy texture, and appearance. On the other hand, agave fructans in prototype ice creams were found to be able to reduce fat, but not fat and sugar simultaneously, showing a significant decrease (p < .05) in terms such as hardness, crystallized texture, gummy texture, and porosity. Based on the PCA results, the analysis accounted for 75.28% of data variability. Full-composition ice creams and one functional ice cream were related to terms such as viscosity, fatty sensation, creamy texture and appearance, dense, gummy, among others. The rest of the commercial ice creams were related to vanilla and caramel flavor and smell, artificial aftertaste, aerated, porosity, among others. Prototype ice creams were related to hard texture, salty and milk flavor, and crystallized texture. Based on the results of the TDS method, all formulations were found to be significantly dominant (5%) in terms such as vanilla flavor and sweet flavor at the beginning of the test. Formulations containing butyric fat and/or vegetable fat, or agave fructans were significantly dominant (5%) in fatty sensation.

Analysis of the Sensory Profile and Physical and Physicochemical Characteristics of Amazonian Cocoa (Theobroma cacao L.) Beans Produced in Different Regions.

The cocoa tree (Theobroma cacao L.) has seeds that after processing become a valuable agricultural commodity in the world. In Brazil, the state of Pará located in the Eastern Amazon is the main producer, accounting for more than 53% of the national production. Although the region is the largest producer, no studies are found in the literature containing data on the sensory quality of the beans. Thus, the purpose of this study is to establish the sensory profile of Amazonian cocoa from the main cocoa-producing regions of the Eastern Amazon (Lower Tocantins River, Northeast, West, Southeast and Trans-Amazon). The sensory profile was established from the Quantitative Descriptive Analysis (QDA), in addition to using an affective test to verify consumer preference for the chocolates produced. Physical, physicochemical and bioactive compound evaluations were carried out. Beans from different regions had a similar sensory profile; however, it was possible to observe some differences in certain descriptor terms. In the physical evaluation, the samples presented an acceptable commercial standard, and the humidity was within the values established by the legislation. It was found that the post-harvest and/or processing parameters had no influence on the quality attributes of cocoa beans.

What Are the Sensory Attributes Associated with Consumer Acceptance of Yellow Oyster Mushrooms (Pleurotus citrinopileatus)?

The oyster mushroom is cultivated globally, renowned for its unique texture and umami flavor, as well as its rich content of nutrients and functional ingredients. This study aims to identify the descriptive sensory characteristics, assess the consumer acceptability of new superior lines and cultivars of yellow oyster mushrooms, in addition to exploring the relationship between these descriptive characteristics and consumer acceptability. Statistical analyses were performed using one-way analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares regression (PLSR). Twenty attributes were delineated, including three related to appearance/color (gray, yellow, and white), four associated with the smell/odor of fresh mushroom (oyster mushroom, woody, fishy, and seafood smells), three pertaining to the smell/odor of cooked mushrooms (mushroom, umami, and savory smells), four describing flavor/taste (sweet, salty, umami, and savory tastes), and five for texture/mouthfeel (chewy, smooth, hard, squishy, and slippery textures). Consumer acceptability tests involved 100 consumers who evaluated overall liking, appearance, overall taste, sweetness, texture, savory taste, MSG taste, smell, color, purchase intention, and recommendation. The general oyster mushroom (548 samples) scored highest in acceptability. Seven attributes, namely fresh mushroom smell, seafood smell (fresh), fishy smell (fresh), umami smell (cooked), nutty smell (cooked), salty taste, and MSG taste with the exception of appearance showed significant differences among samples (p < 0.001). The three yellow oyster mushroom samples were strongly associated with attributes like hardness, softness (texture), sweet taste (745 samples), MSG taste, salty taste, squishy texture, and fishy smell (483 and 629 samples). The development of sensory lexicons and increasing consumer acceptance of new superior lines and cultivars of yellow oyster mushroom will likely enhance sensory quality and expand the consumer market, aligning with consumer needs and preferences.

AI as a Medical Device Adverse Event Reporting in Regulatory Databases: Protocol for a Systematic Review.

BACKGROUND: The reporting of adverse events (AEs) relating to medical devices is a long-standing area of concern, with suboptimal reporting due to a range of factors including a failure to recognize the association of AEs with medical devices, lack of knowledge of how to report AEs, and a general culture of nonreporting. The introduction of artificial intelligence as a medical device (AIaMD) requires a robust safety monitoring environment that recognizes both generic risks of a medical device and some of the increasingly recognized risks of AIaMD (such as algorithmic bias). There is an urgent need to understand the limitations of current AE reporting systems and explore potential mechanisms for how AEs could be detected, attributed, and reported with a view to improving the early detection of safety signals. OBJECTIVE: The systematic review outlined in this protocol aims to yield insights into the frequency and severity of AEs while characterizing the events using existing regulatory guidance. METHODS: Publicly accessible AE databases will be searched to identify AE reports for AIaMD. Scoping searches have identified 3 regulatory territories for which public access to AE reports is provided: the United States, the United Kingdom, and Australia. AEs will be included for analysis if an artificial intelligence (AI) medical device is involved. Software as a medical device without AI is not within the scope of this review. Data extraction will be conducted using a data extraction tool designed for this review and will be done independently by AUK and a second reviewer. Descriptive analysis will be conducted to identify the types of AEs being reported, and their frequency, for different types of AIaMD. AEs will be analyzed and characterized according to existing regulatory guidance. RESULTS: Scoping searches are being conducted with screening to begin in April 2024. Data extraction and synthesis will commence in May 2024, with planned completion by August 2024. The review will highlight the types of AEs being reported for different types of AI medical devices and where the gaps are. It is anticipated that there will be particularly low rates of reporting for indirect harms associated with AIaMD. CONCLUSIONS: To our knowledge, this will be the first systematic review of 3 different regulatory sources reporting AEs associated with AIaMD. The review will focus on real-world evidence, which brings certain limitations, compounded by the opacity of regulatory databases generally. The review will outline the characteristics and frequency of AEs reported for AIaMD and help regulators and policy makers to continue developing robust safety monitoring processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48156.

Optimization of HS-SPME/GC-MS Method for Determining Volatile Organic Compounds and Sensory Profile in Cocoa Honey from Different Cocoa Varieties (Theobroma cacao L.).

This study aimed to develop an analytical method using HS-SPME/GC-MS to determine the volatile organic compound (VOC) profiles and evaluate the sensory attributes of cocoa honey from four cocoa varieties (CCN51, PS1319, SJ02, and Parazinho). Using a multivariate factorial experimental design, the HS-SPME/GC-MS method was optimized to determine the VOC profiles. Twenty previously trained tasters participated in the ranking descriptive analysis, while 108 consumers participated in the acceptance and purchase intention tests. A total of 84 volatile organic compounds were identified from various chemical classes, including acids, alcohols, aldehydes, esters, ketones, monoterpenes, oxygenated monoterpenoids, sesquiterpenes, and oxygenated sesquiterpenoids. Palmitic acid was the compound found in the highest concentration in all varieties (5.13-13.10%). Multivariate analysis tools identified key compounds for differentiation and grouping of the samples. The results revealed that the variety significantly influenced both the VOCs' concentrations and sensory profiles. The CCN51, PS1319, and SJ02 varieties exhibited the highest diversity of VOCs and sensory attributes. Notably, the SJ02 and CCN51 varieties demonstrated superior acceptability and purchase intention, with means ranging from 7.21 and 7.08 to 3.71 and 3.56, respectively. These results indicate their potential as promising sources of cocoa honey for the food industry.

Health Care Workers' Motivations for Enrolling in Massive Open Online Courses During a Public Health Emergency: Descriptive Analysis.

Background: Massive open online courses (MOOCs) are increasingly used to educate health care workers during public health emergencies. In early 2020, the World Health Organization (WHO) developed a series of MOOCs for COVID-19, introducing the disease and strategies to control its outbreak, with 6 courses specifically targeting health care workers as learners. In 2020, Stanford University also launched a MOOC designed to deliver accurate and timely education on COVID-19, equipping health care workers across the globe to provide health care safely and effectively to patients with the novel infectious disease. Although the use of MOOCs for just-in-time training has expanded during the pandemic, evidence is limited regarding the factors motivating health care workers to enroll in and complete courses, particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). Objective: This study seeks to gain insights on the characteristics and motivations of learners turning to MOOCs for just-in-time training, to provide evidence that can better inform MOOC design to meet the needs of health care workers. We examine data from learners in 1 Stanford University and 6 WHO COVID-19 courses to identify (1) the characteristics of health care workers completing the courses and (2) the factors motivating them to enroll. Methods: We analyze (1) course registration data of the 49,098 health care workers who completed the 7 focal courses and (2) survey responses from 6272 course completers. The survey asked respondents to rank their motivations for enrollment and share feedback about their learning experience. We use descriptive statistics to compare responses by health care profession and by World Bank country income classification. Results: Health care workers completed the focal courses from all regions of the world, with nearly one-third (14,159/49,098, 28.84%) practicing in LICs and LMICs. Survey data revealed a diverse range of professional roles among the learners, including physicians (2171/6272, 34.61%); nurses (1599/6272, 25.49%); and other health care professionals such as allied health professionals, community health workers, paramedics, and pharmacists (2502/6272, 39.89%). Across all health care professions, the primary motivation to enroll was for personal learning to improve clinical practice. Continuing education credit was also an important motivator, particularly for nonphysicians and learners in LICs and LMICs. Course cost (3423/6272, 54.58%) and certification (4238/6272, 67.57%) were also important to a majority of learners. Conclusions: Our results demonstrate that a diverse range of health care professionals accessed MOOCs for just-in-time training during a public health emergency. Although all health care workers were motivated to improve their clinical practice, different factors were influential across professions and locations. These factors should be considered in MOOC design to meet the needs of health care workers, particularly those in lower-resource settings where alternative avenues for training may be limited.

Zinc Supplementation Improves Texture, Oxidative Stability of Caciotta Cheese and Reduces Biogenic Amines Production.

Zinc is essential for animals, playing a vital role in enzyme systems and various biochemical reactions. It is crucial to ensure a sufficient intake of zinc through the diet to maintain efficient homeostasis. Only few studies on zinc effect in cow lactating diet evaluated the effects on milk and cheese quality, with conflicting findings. 24 cows of the Friesian breed were divided into two groups (CTR: control and TRT: treated group). Cows were selected for age, body weight, parity and phase of lactations (mid lactation, 140-160 days). CTR diet contained 38 mg/kg of Zn and TRT diet was supplied with 120 mg/kg of complete feed for 60 days. The objective of current investigation was to evaluate the impact of a dietary Zinc Oxide (ZnO) integration of lactating Friesian cows on chemical composition, zinc content, fatty acid and proteic profile, ammine content, pH, aw, texture, and sensory profile of cheese and to improve the chemical-nutritional quality of milk and cheese. The results showed that ZnO supplementation reduced mesophilic aerobic bacteria and Presumptive Pseudomonas spp. growth, proteolysis, biogenic amines content, lipid oxidation, odour intensity and sour and increased hardness, gumminess, chewiness, elasticity of cheese. Biogenic amines are considered an important aspect of food safety. ZnO integration in cow diet could represent a promising strategy for improving the quality, the safety and shelf-life of caciotta cheese.

Analysis of enterobiasis in the Czech Republic in 2018-2022. / Analýza výskytu enterobióz v Ceské republice v letech 2018­2022.

AIM: Pinworm infection (known as enterobiasis or oxyuriasis) is one of the most common parasitic diseases globally and in the Czech Republic (CZ). The aim of this study is to analyse the available epidemiological data on the incidence of enterobiasis in the CZ from 2018-2022. METHODS: A descriptive analysis was done of enterobiasis (ICD-10 code B80) data reported to the electronic Infectious Disease Information System in the CZ from 2018 to 2022. Data processing and analysis were conducted using MS Excel 2016. Univariate and multivariate logistic regression analyses were performed to assess the association between the probability of hospitalization and categorical variables using STATA version 17. The ECDC Map Maker tool (EMMa) was used to create the incidence map. RESULTS: A total of 4,836 cases were reported during the study period, with an average annual incidence of 9.1 cases per 100,000 population. The highest number of cases occurred in 2019 (n = 1,174), and the lowest in 2021 (n = 780). The disease was most common in the paediatric population, with the highest average age-specific incidence rates observed in children aged 5-9 years (80.9 per 100,000 population) and 10-14 years (42.3 per 100,000 population). Of 14 administrative regions of the CZ, the Olomouc Region had the highest average annual incidence (28.7 per 100,000 population), while the Pilsen Region had the lowest (2.2 per 100,000 population). A total of 472 (9.8%) patients needed hospitalization, most of them in the categories 10-14 years (n = 200, 42.4%) and 5-9 years (n = 178, 38%). The highest hospitalization rate was found in the age group 75+ (36.4%). A significantly higher probability of hospitalization was found in the age groups 6-19 years and 65+ compared to working-age population with enterobiasis. A significantly lower probability of hospitalization was seen in 2020-2022 compared to 2019. No difference in the hospitalization rates was noted between genders. No enterobiasis-related death was reported during the study period. The disease occurs year-round. A decrease in reported cases was observed annually during the school summer holidays in July and August. Neither outbreak nor imported cases were noted. CONCLUSION: Given that enterobiasis is often asymptomatic, many cases are not captured in the surveillance system. The Czech prevalence data indicate that it mainly affects the paediatric population. Therefore, preventive measures and programs should primarily target children.

Markers of sensory dynamics in phenols-rich virgin olive oils under optimal storage conditions.

Early changes in sensory quality of phenols-rich virgin olive oil (VOO) and their relationship with the chemical changes are less studied in the literature. Therefore, the objective of this study was to propose a predictive model of dynamics of sensory changes based on specific chemical markers. The evolution of the sensory quality of phenol-rich VOOs from Tuscan cultivars stored under optimal storage conditions (i.e., absence of light, no O2 exposure, low temperature) was investigated using a multi-step methodological approach combining sensory (official sensory analysis (so-called Panel Test), Descriptive Analysis and Temporal Dominance of Sensation) and chemical measurements. The sensory map from descriptive data was related to the phenolic and volatile profiles, measured using HPLC-DAD and HS-SPME-GC-MS, respectively. A predictive model of the sensory changes over storage based on chemical compounds was developed. Results showed that very early changes involving phenolic and volatile compounds profiles occur in VOOs stored under optimal storage conditions, which turn in changes in sensory properties evaluated by the official panel test, the descriptive analysis and the temporal dominance of sensation. Furthermore, a chemical marker of sensory dynamics of oils during storage was identified as the ratio between two groups of secoiridoids. The proposed model, supported by the mentioned chemical marker, has the potential of improving the control of sensory changes in phenols-rich virgin olive oils during storage in optimal conditions.

Comparing the sensory properties of commercially available animal and plant-based burgers.

The number of plant-based meat products on supermarket shelves around the world has grown in recent years however reproducing the sensory experience of eating meat remains a challenge. This study aims to evaluate the sensory gaps between animal and plant-based meat products, specifically burger-type products, from the Australian market. The sample set of 19 commercially available burgers comprises 8 animal-based burgers prepared using beef, chicken, kangaroo, pork, or turkey and 11 high protein plant-based burgers. Vegetable patties are beyond the scope of this study. A trained sensory panel (n = 14) determined the major differences in aroma, texture, flavor, and aftertaste between meat and meat analogues during oral processing, particularly those that may impact consumer acceptability. The animal-based burgers scored high for meaty (aroma), meaty (flavor), and umami but not legume, vegetative, bitterness, and lingering spice attributes. They also received higher average scores for juiciness, fattiness, and final moistness than the plant-based burgers but scored lower in cohesiveness. The plant-based burgers scored high for legume and bitterness but not meaty (aroma), meaty (flavor), and umami attributes. Improving current products and designing new products with desirable sensory properties will enhance consumer acceptability and reinforce recent growth in the plant-based meats market.

Key Aroma Differences in Volatile Compounds of Aged Feng-Flavored Baijiu Determined Using Sensory Descriptive Analysis and GC×GC-TOFMS.

Sensory descriptive analysis of aged feng-flavored Baijiu liquor indicated notable differences in samples of different ages. The samples of freshly distilled Baijiu and those with shorter storage times exhibit bran and fresh green flavors, whereas, with increasing storage time, honey, sweet, and floral fragrances are gradually enhanced. Samples of feng-flavored Baijiu were prepared using headspace solid-phase microextraction, followed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. A total of 496 compounds were identified in all samples, mainly categorized as 14 groups of substances, including esters and aldehydes. Interestingly, 42 of these substances were found in Feng-flavored Baijiu for the first time. Chemometrics was used to analyze the key differential compounds. First, 143 differential compounds closely related to aging were preliminarily screened, and principal component analysis revealed that these compounds were separated by baijiu age. Then, 65 differential compounds were selected by partial least squares discriminant analysis. Furthermore, 43 key differential compounds were selected by combined analysis with variable importance in projection and Pearson correlation coefficients. Partial least squares regression was used to study the correlation between the sensory properties and key differential compounds, and the results indicated that most compounds were closely related to the aging period of the Baijiu. The results of this study provide a theoretical basis and reference for flavor research on feng-flavored Baijiu.

Safety Profile of the Trastuzumab-Based ADCs: Analysis of Real-World Data Registered in EudraVigilance.

Trastuzumab (T) and tyrosine kinase inhibitors (TKIs) are among the first-line treatments recommended for HER2-positive breast cancer. More recently, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) have been authorized, and they represent the second-line therapy in this type of cancer. The present study aimed to evaluate adverse drug reactions (ADRs) associated with T-based ADCs that were spontaneously reported in EudraVigilance-the European pharmacovigilance database. Out of 42,272 ADRs reported for currently approved ADCs on the market, 24% of ADRs were related to T-DM1, while 12% of ADRs were related to T-DXd. T-DM1 had a higher probability of reporting eye, ear and labyrinth, and cardiac and hepatobiliary ADRs, while T-DXd had a higher probability of reporting respiratory, thoracic and mediastinal, blood and lymphatic system, metabolism and nutrition, and gastrointestinal ADRs. The present research found that in terms of hematological disorders, T-DM1 and T-DXd had a higher probability of reporting ADRs than TKIs. Moreover, the data showed that T-DM1 seemed to have a higher risk of cardiotoxicity than T-DXd, while T-DXd had a higher probability of reporting metabolism and nutrition disorders than T-DM1.

Key umami taste contributors in Longjing green tea uncovered by integrated means of sensory quantitative descriptive analysis, metabolomics, quantification analysis and taste addition experiments.

Umami taste is a key criteria of green tea quality evaluation. The aim of this study was to comprehensively explore the key umami taste contributors in Longjing tea. The taste and molecular profiles of 36 Longjing green tea infusions were characterized by sensory quantitative descriptive analysis and LC-MS based metabolomics, respectively. By uni-/multi-variate statistical analysis, 84 differential compounds were screened among tea infusions with varied umami perceptions. Among them, 17 substances were identified as candidate umami-enhancing compounds, which showed significant positive correlations with umami intensities. Their natural concentrations were accurately quantified, and their umami taste-modifying effects were further investigated by taste addition into glutamic acid solution. Glutamic acid, aspartic acid, glutamine, theanine, phenylalanine, histidine, theogallin, galloylglucose, 1,2,6-trigalloylglucose significantly enhanced the umami taste. This study uncovered for the first time of some bitter amino acids and galloylglucose homologous series as important umami-enhancers, which provided a novel perspective into the tea taste.

Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

BACKGROUND: Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. OBJECTIVE: Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. METHODS: We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. RESULTS: Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. CONCLUSIONS: Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.