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Bio-orthogonal labeling of vesicles conjugated with fluorescent molecular groups, enables in vivo bioimaging to monitor their behavior, thus aiding in diagnostics or revealing the internalization mechanisms of extracellular vesicles (EVs). Orthogonally based magnetic beads, microfluidics, and microarray chips specifically and in a high-throughput manner isolate EVs derived from various cancers for diagnosis of diseases and cancer development. By loading drugs onto the surface of EVs or forming covalent bonds between EVs and cells through bio-orthogonal methods, the therapeutic efficiency of EVs can be enhanced. Bio-orthogonal glycometabolism enables EVs to directly target tumor cells and their derived EVs in vivo , thereby inhibiting tumor metastasis and growth. Extracellular vesicle (EV)-based therapeutics have gained substantial interest in the areas of drug delivery, immunotherapy, and regenerative medicine. However, the clinical translation of EVs has been slowed due to limited yields and functional heterogeneity, as well as inadequate targeting. Engineering EVs to modify their inherent function and endow them with additional functions has the potential to advance the clinical translation of EV applications. Bio-orthogonal click chemistry is an engineering approach that modifies EVs in a controlled, specific, and targeted way without compromising their intrinsic structure. Here, we provide an overview of bio-orthogonal labeling approaches involved in EV engineering. We also present the isolation methods of bio-orthogonally labeled vesicles using magnetic beads, microfluidics, and microarray chip technologies. We highlight the in vivo applications of bio-orthogonal labeling EVs for diagnosis and therapy, especially the exciting potential of bio-orthogonal glycometabolic engineered EVs for targeted therapies. [ABSTRACT FROM AUTHOR]

Here, we provide an overview of the key factors to consider when using fluorescence nanoscopy (FN), including biological questions that can be addressed and aspects that might improve the reliability and effectiveness of FN experiments. We cover the main aspects related to sample preparation, including the selection of appropriate fixation, affinity-based labels, and fluorescent dyes. We discuss current limitations and possible future developments in the field that would facilitate a broader application of FN. We discuss multiplexing possibilities (allowing the simultaneous detection of multiple targets in a single experiment), live cell imaging for the study of cellular and molecular dynamic processes, and quantitative workflows. Recently, biologists have gained access to several far-field fluorescence nanoscopy (FN) technologies that allow the observation of cellular components with ~20 nm resolution. FN is revolutionizing cell biology by enabling the visualization of previously inaccessible subcellular details. While technological advances in microscopy are critical to the field, optimal sample preparation and labeling are equally important and often overlooked in FN experiments. In this review, we provide an overview of the methodological and experimental factors that must be considered when performing FN. We present key concepts related to the selection of affinity-based labels, dyes, multiplexing, live cell imaging approaches, and quantitative microscopy. Consideration of these factors greatly enhances the effectiveness of FN, making it an exquisite tool for numerous biological applications. [ABSTRACT FROM AUTHOR]

A review of new oncology indications approved by the European Medicines Agency (EMA) for 2012-2016 showed that 33% of new drugs had labeling based on patient-reported outcomes (PROs). We reviewed labeling text based on PRO endpoints for new oncology indications approved during 2017-2021. New oncology drugs approved by EMA to treat indications of cancers during 2017-2021 were identified from the EMA website. PRO-related language reported in EMA summaries of product characteristics (SmPCs) were summarized and compared with similar findings reported for oncology indications approved during 2012-2016. Review documents by the EMA during 2017-2021 were available for 49 new oncology drugs for 70 cancer indications. Submissions for 52 (74.3%) of the 70 indications included PRO data for EMA review. Of all submissions, 14 (20.0%) approvals contained PRO-related language in the SmPC. Broad concepts such as health-related quality of life were most common and found in 8 of 14 (57.1%) PRO-related labels. PRO-related language appeared in SmPCs for 20% of all indications of new oncology drugs approved by EMA during 2017-2021 compared with approximately 33% of EMA approvals during 2012-2016. PRO-related labeling during the same periods showed a greater decline (from 47% to 27%) for indications of new oncology drugs that also included PRO data. One possible reason for this decline may be the increase in open-label studies from 62% between 2012 and 2016 to approximately 79% between 2017 and 2021. • A previous review of new oncology indications approved by the European Medicines Agency for 2012 to 2016 showed that 33% of indications had labeling based on patient-reported outcomes (PROs). Of these, the most commonly included concepts were related to symptoms. • The current review, undertaken for 2017 to 2021, shows that PRO-related labeling was included in only 20% of new oncology indications approved by the European Medicines Agency—a decline of approximately 13%. In this period, broad concepts such as health-related quality of life represented the concepts most commonly included in labeling with PRO language. • One possible reason for the discrepancy observed during these 2 periods may be related to the more frequent use of open-label studies seen in the current review. [ABSTRACT FROM AUTHOR]

Machine learning is a suitable pattern recognition technique for detecting correlations between data. In the case of unsupervised learning, the groups formed from these correlations must receive a label, which consists of describing them in terms of their most relevant attributes and their respective ranges of values so that they are understood automatically. In this research work, this process is called labeling. However, a challenge for researchers is to establish the optimal number of groups submitted to grouping, which influences the performance of this process. Therefore, this research aims to provide an inference approach to the number of clusters used in the clustering based on the range of attribute values, followed by automatic data labeling to maximize the understanding of the groups obtained. This methodology was applied to four databases, and the results show that it contributes to the interpretation of groups since it generates more accurate labels with a hit rate above 93%. [ABSTRACT FROM AUTHOR]

An antimagic labeling of a graph G with n vertices and m edges is a bijection from the set of edges of G to { 1 , 2 , ... , m } such that all n vertex-sums are pairwise distinct, where the vertex-sum of a vertex is the sum of labels on the edges incident with it. We say a graph is antimagic if it has an antimagic labeling. In 1990, Hartsfield and Ringel conjectured every connected graph with at least three vertices is antimagic, which is known as the Antimagic Labeling Conjecture. This conjecture seems difficult, and it has not been certified for trees so far. Recently, it has been verified to be true for regular bipartite graphs and regular graphs independently. However, it remained unknown whether every biregular bipartite graph is antimagic. In this paper, we almost answer this question affirmatively. [ABSTRACT FROM AUTHOR]

One of the biggest challenges for artificial intelligence in industry is the lack of labeled application data. Particularly for time series data, labeling requires a large amount of time for data preparation and expert knowledge both in data analysis and in the application domain. In this work, we propose a methodology for labeling time series solving the two barriers identified above in an additive manufacturing use case. Our approach correlates spatial and temporal features of process defects by means of a spatial sensor. By applying our method, we were able to achieve shorter labeling time while obtaining high-quality labels. [ABSTRACT FROM AUTHOR]

The global market for plant-based products is increasing at a faster rate than the market for traditional dairy products. Current regulations provide standards for those traditional dairy products but lack the same regulations for similar plant-based products. Resulting from this difference in regulation is consumer confusion over the differences between the 2 types of products. The purpose of this review paper was to understand how the differences between traditional dairy and plant-based dairy-like products could affect litigation by consumer and dairy manufacturers against potential misleading labeling. A review of the available literature found 4 relevant articles for analysis. Consumers and manufacturers can pursue claims against potentially misleading product labeling but must provide sufficient evidence to prove deception or injury. Past litigation against plant-based products for being misleading has ruled in favor of the plant-based defendants. These rulings were based on the notion that reasonable consumers would not be misled. Consumer and manufacturing advocates for dairy products should focus more resources on the education of consumers rather than litigation if the goal is to promote dairy products. Long-term regulatory changes could be made through the Defending Against Imitations and Replacements of Yogurt, Milk, and Cheese to Promote Regular Intake of Dairy Everyday Act, which is currently under legislative review. [ABSTRACT FROM AUTHOR]

To explore whole-grain food definitions in labeling and relevance to consumers and the food industry. Semistructured focus groups and interviews. Online. Consumers (n = 43) aged ≥ 18 years currently purchasing/consuming grain foods. Food industry participants (n = 17) currently/recently employed within grain food companies. Impact of using whole-grain food definitions in labeling. Inductive thematic analysis. Six major themes included: consumer knowledge and understanding of whole-grain foods; factors affecting consumer grain food choices; consumer skepticism of labeling; consumer preferences toward whole-grain labeling; acceptability and feasibility of whole-grain food definitions in the food industry; and food innovation/reformulation. For the food industry, definitions impact feasibility, food innovation, and reformulation. Skepticism affected consumer knowledge and understanding, impacting grain food choice and their preference regarding whole-grain labeling. Consumers preferred whole grain in the name of a food and placing the percent of whole grain on the front-of-pack. Our findings suggest that definitions and regulations, consumer education, and strategies addressing factors influencing consumer choice are needed to improve population whole-grain intakes. Future research may consider formal regulation and implementation of standardized whole-grain food definitions in labeling and explore the subsequent impact on consumer choice and whole-grain intake. [ABSTRACT FROM AUTHOR]

We posit that strict exponential loss of label in blood after reinfusion of 3H-labeled neutrophils in humans can be explained by the redistribution of labeled cells into a large neutrophil compartment in tissues, rather than by cell death. The lifespans and post-mitotic transfer times (PMTTs) of murine neutrophils are significantly shorter than those of human neutrophils, which precludes the direct translation of mouse data to humans. The long PMTT in humans precludes an effect of a circadian rhythm of neutrophil progenitors on the daily production and death of mature neutrophils. The mobilization by corticosteroids of extravasated labeled neutrophils in calves indicates that the disappearance of label of reinfused cells is not an indication of cell death. Current estimates of human neutrophil half-lives are based on assumptions for which experimental data are opposing or nonexisting. We propose that in homeostasis in humans, the oldest neutrophils are the first to die following a so-called conveyor belt model, as opposed to by random chance, as currently used in models estimating neutrophil half-lives. The correct interpretation of the available published data regarding the lifespan kinetics of the human neutrophil compartment is key for understanding the role of neutrophils in health and disease. The half-life of human neutrophils is still controversial, with estimates ranging from 7–9 h to 3.75 days. This debate should be settled to understand neutrophil production in the bone marrow (BM) and the potential and limitations of emergency neutropoiesis following infection or trauma. Furthermore, cellular lifespan greatly influences the potential effect(s) neutrophils have on the adaptive immune response. We posit that blood neutrophils are in exchange with different tissues, but particularly the BM, as it contains the largest pool of mature neutrophils. Furthermore, we propose that the oldest neutrophils are the first to die following a so-called conveyor belt model. These guiding principles shed new light on our interpretation of existing neutrophil lifespan data and offer recommendations for future research. [ABSTRACT FROM AUTHOR]

Activities involved in the production of certain advanced therapy medicinal products (ATMPs) require standardized approaches to mononuclear cell procurement to ensure the highest product quality, safety and process efficiency. These aims must be achieved while meeting regulatory and accreditation requirements for the procurement of mononuclear cells as starting materials. Mononuclear cells constitute the starting materials for many ATMPs, and this article sets out recommendations for procurement by clinical apheresis, addressing the variation among existing working practices and different manufacturers' requirements that currently poses a challenge when managing multiple different protocols. [ABSTRACT FROM AUTHOR]

Background Offspring of obese rodents develop a metabolic phenotype that favors fat deposition. Data regarding the impact of maternal obesity programing of offspring fuel usage in humans is scarce. Objective The objective of this study was to explore the association between maternal weight status and dietary palmitate oxidation (DPO) in 2-y-old offspring, taking into consideration potential confounders and modifiers. Methods Women (n  = 56) were enrolled by the first trimester of gestation. Maternal physical activity (PA; measured with accelerometers) at enrollment and gestational weight gain (GWG) were measured. Offspring sex, race, and breastfeeding (BF) duration were self-reported. Human milk (HM) composition was determined at 6 mo postpartum. At age 2 y, dietary quality [healthy eating index (HEI)] and parental feeding practices [Child Feeding Questionnaire (CFQ)] were assessed. DPO in 2-y-olds (2-yo-DPO) was measured using deuterated palmitic acid. Generalized linear regression analysis was used to model the associations of 2-yo-DPO with maternal weight status [normal weight (NW), BMI <25 (in kg/m2) compared with excessive weight (EW), BMI ≥25]. Results DPO was higher in offspring of women with EW compared with NW (2.1 ± 1.2%/h compared with 1.4 ± 0.7%/h, P  = 0.03). Maternal weight status interacted with BF duration in association with 2-yo-DPO (log ß : 0.05, P  = 0.04). Specifically, 2-yo-DPO was higher in the EW compared with NW group if BF duration was ≥9 mo. HM insulin (log ß : 0.35, P  = 0.002) and HM leptin (log ß : 0.81, P  = 0.001) concentrations directly associated with 2-yo-DPO. PA (log ß : 0.06, P  = 0.013), parental feeding restriction (log ß : 0.05, P  < 0.0001), and male sex (log ß : 0.54, P  < 0.001) were positively associated with 2-yo-DPO. HEI was negatively associated with 2-yo-DPO (log ß :−0.03, P  < 0.0001). Conclusions Higher 2-yo-DPO in offspring of women with EW compared with NW were driven by BF duration. Higher HM insulin and leptin concentrations in women with EW may explain these finding. More studies are needed to confirm these results. This trial was registered at clinicaltrials.gov as NCT03281850. [ABSTRACT FROM AUTHOR]

Low-calorie sweeteners (LCSs) are increasingly being used worldwide, including in foods and beverages commonly consumed by children. To examine the prevalence of LCSs in packaged foods and beverages sold in Brazil, whether LCSs are added to products with advertising directed to children, and whether foods and beverages with LCSs include front-of-package (FoP) LCS-related health and nutrition claims. Cross-sectional study. A sample (n = 11,434) of packaged foods and beverages sold by the top 5 largest Brazilian food retailers was examined to identify LCSs and added sugars, and a subsample (n = 3491) was examined to determine the presence of advertising directed to children and FoP LCS-related claims in foods and beverages with LCSs. The prevalence of foods and beverages with different types of LCSs in the Brazilian food supply, among ultra-processed foods and beverages and among foods and beverages with added sugars, were measured. Foods and beverages with advertising directed to children were checked to see if these products had LCSs and how many products with LCSs had FoP labels with LCS-related claims. Mean and 95% CIs were used to determine the overall prevalence of foods and beverages with LCSs and in the different assessed stratifications. The prevalence of LCSs was 9.3% (95% CI 8.8-9.9) in Brazilian packaged foods and beverages, 14.6% (95% CI 13.8-15.4) in ultra-processed products alone, and 5.7% (95% CI 4.2-7.7) in foods and beverages with advertising directed to children. About 83% of food and beverage with LCSs were also sweetened with added sugars. LCSs were most frequently added to nonalcoholic sweetened beverages, breakfast cereals, and granola bars. Forty percent of foods and beverages with LCS did not present any FoP LCS-related claim. This study shows that LCSs are present in 15% of ultra-processed foods and beverages in Brazil, largely used in combination with added sugars, and are found in foods and beverages with advertising directed to children. Clearer FoP information regarding the presence of LCSs, in particular in products with advertising directed to children, can help consumers make more informed choices regarding LCS consumption. [ABSTRACT FROM AUTHOR]

The 1990s saw rapid growth in international activity in hematopoietic cell transplantation. As national donor registries were established and international collaboration increased, a need to transfer cellular therapy products across national borders emerged. A lack of international standards for identification, terminology and labeling resulted in significant challenges for import and export. Twenty years of effort by a large group of experts supported by professional societies and accreditation bodies has today achieved a high degree of standardization. This review highlights the main landmarks in this journey and serves as a reminder of the importance of taking the "long view" when working toward international standardization. It demonstrates the need for continual maintenance and enhancement of standards to meet the changing needs of the cell therapy industry and highlights recent developments in ISBT 128. [ABSTRACT FROM AUTHOR]

Background: The Prescribing Information (PI) is the US Food and Drug Administration (FDA)'s primary tool for communicating a summary of the essential scientific information needed for the safe and effective use of a prescription drug to healthcare providers.[1] One challenge with this type of communication is balancing the need to be thorough with the need to be concise.Objectives: This study aimed to explore physicians' preferences for and understanding of specific content and formatting in the PI. This study also explored physicians' use of and perceptions of the PI.Methods: Seventy semi-structured qualitative interviews were conducted with primary care physicians (n = 35) and physicians from a wide range of specialties (n = 35) using web conferencing technology. Using fictitious PI examples, the guide assessed physicians' interpretation of language and preferences for how certain information is organized and communicated in select sections of the PI. The interview guide also included questions about the resources physicians use to find information about prescription drugs, when and how physicians access the PI, and their perceptions of the PI.Results: The findings suggest that of the content and formatting items surveyed, physicians had the greatest preference for: (1) uniformly specifying the age group for which the drug is indicated in the INDICATIONS AND USAGE section, even for medical conditions that are highly associated with only one particular age group (e.g., adult patients), and (2) uniformly including administration information in relation to food (e.g., "with or without food") in the DOSAGE AND ADMINISTRATION section for drugs with oral dosing. The findings also suggest that including a long list of interacting drug examples in the DRUG INTERACTIONS section may be misinterpreted to be a comprehensive list.Conclusion: This qualitative research suggests physicians may prefer more clarity in some sections of the PI. [ABSTRACT FROM AUTHOR]

• Perceived environmental friendliness of shopping sequences is disproportionately influenced by the ending. • Purchase frequency appears to have a larger effect than purchase quantity. • The accumulated perceived eco-friendliness of shopping sequences can influence willingness to buy subsequent eco-friendly items. Can memory of eco-labeling bias how consumption is perceived and influence subsequent consumer decisions? We report three experiments showing that the perceived environmental friendliness of simulated shopping sequences is disproportionately influenced by what happens at the end of the sequence. For example, sequences that ended with a high carbon footprint item were perceived as less environmentally friendly than other sequences with the same content but with items in different order—a recency effect (Experiments 1–3). Judgments depended more on how often environmentally significant items were purchased than on the quantity of those items (Experiment 2). Furthermore, after completing a shopping sequence that was perceived as relatively harmful to the environment, participants were more prone to select a comparably expensive eco-labeled item over a cheaper but less environmentally friendly item in subsequent purchase decisions—a spillover effect (Experiment 3). The results stress the role of memory in environmentally significant consumer behavior. [ABSTRACT FROM AUTHOR]

• Characterization of fluorescent dye binding sites on antibodies. • Structure function analysis by mass spectrometry. • To have an inert tracer, minimal labeling is highly effective but not enough. • An inert tracer for determination of residence time distribution in chromatography. Fluorescently labeled antibodies are widely used to visualize the adsorption process in protein chromatography using confocal laser scanning microscopy (CLSM), but also as a tracer for determination of residence time distribution (RTD) in continuous chromatography. It is assumed that the labeled protein is inert and representative of the unlabeled antibody, ignoring the fact that labeling with a fluorescent dye can change the characteristics of the original molecule. It became evident that the fluorescently labeled antibody has a higher affinity toward protein A resins such as MabSelect Sure. This can be due to slight differences in hydrophobicity and net charge, which are caused by the addition of the fluorescent dye. However, this difference is eliminated when using high salt concentrations in the adsorption studies. In this work, the site occupancy of two labeled antibodies, MAb1 (IgG1 subclass) and MAb2 (IgG2 subclass) conjugated with the fluorescent dye Alexa Fluor™ 488 was elucidated by intact mass spectrometry (MS) and peptide mapping LC-MS/MS, employing a sequential cleavage with Endoproteinase Lys-C and trypsin and in parallel with chymotrypsin alone. It was shown that the main binding site for the dye was a specific lysine in the heavy chains of the MAb1 and MAb2 molecules, in positions 188 and 189 respectively. Other lysine residues distributed throughout the protein sequence were labeled to a lot lesser extent. The labeled antibody had a slightly different affinity to MabSelect Sure although its primary binding site (to Protein A) was not affected by labeling, despite the secondary region responsible for binding to the protein A was partly labeled. Overall, the fluorescent-labeled antibodies are a good compromise as an inert tracer in residence time distribution and chromatography studies because they are much cheaper than isotope-labeled antibodies; However, the differences between the labeled and unlabeled antibodies should be considered. [ABSTRACT FROM AUTHOR]

[Display omitted] Prenylation (isopentenylation), a key post-transcriptional modification with a hydrophobic prenyl group onto the biomacromolecules such as RNA and proteins, influences their localization and function. Prenyltransferases mediate this process, while cytokinin oxidases degrade the prenylated adenosine in plants. This review summarizes current progress in detecting prenylation modifications in RNA across species and their effects on protein synthesis. Advanced methods have been developed to label and study these modifications in vitro and in vivo , despite challenges posed by the inert chemical properties of prenyl groups. Continued advancements in bioorthogonal chemistry promise new tools for understanding the precise biological functions of prenylated RNA modifications and other related proteins. [ABSTRACT FROM AUTHOR]

Due to the high prevalence and severe consequences of falls among older people, pre-impact fall detection algorithms which aim to detect falls before body-ground impacts are of critical importance. The success of existing algorithms based on wearable sensors relies heavily on numerous labeled data from both falls and activities of daily living (ADLs). However, fall data is much more difficult to acquire compared with ADLs, and moreover, labeling falling period apart from ADLs is laborious and time-consuming. To this end, we proposed a novel semi-supervised model for pre-impact fall detection, called Semi-PFD, which maximizes the utilization of easily obtainable ADL data and reduces the dependency on labeled fall data. This model was evaluated on two large-scale public fall datasets (KFall and SisFall) and compared with its supervised baseline under different ratios of fall data. Cross-validation results showed that Semi-PFD outperformed the supervised baseline across all conditions on both datasets. More importantly, Semi-PFD achieved considerable improvement of 2–4% F1-score when the ratios of fall data were low (≤23.1%). Remarkably, with only 76.9% of fall data, Semi-PFD achieved comparable and even higher F1-scores than the state-of-the-art benchmark models which utilized 100% of fall data. We further observed that the incorporation of unsupervised training in Semi-PFD mitigated the typical overconfidence problem associated with supervised training without affecting lead time. These findings underscore Semi-PFD's practical potential, reducing the burden of fall data collection and labeling while maintaining superior performance. [ABSTRACT FROM AUTHOR]

Objective: Despite the appeal of early intervention in psychosis, there is concern that identifying youth as having high psychosis risk (PR) may trigger stigma. This study employed a pre-post design to measure change in PR participants' emotions about PR upon being told of their PR status and according to whether this was the first time receiving this information.Methods: Participants (n = 54) identified as at PR via structured interview rated their emotions about PR before and after being told they were at PR. Qualitative analyses explored the valence of participant reflections on being given this information.Results: Participants reported significantly less negative emotion after being told of their PR status (p < .001), regardless of whether they were hearing this for the first time (p = .72). There was no change in positive emotions or the predominant belief that they should keep their PR status private. Most participants commented positively about the process of feedback but negatively about its impact on their self-perceptions and/or expectations of others' perceptions of them.Conclusion: This is the first study to collect pre-post data related to being told one is at PR and to examine quantitative and qualitative responses across and within individuals. For a majority of participants, clinical feedback stimulated negative stereotypes even as it relieved some distress. To actively address internalized stigma, clinicians providing feedback to PR youth must attend to the positive and negative impacts on how youth think about themselves as well as how they feel. [ABSTRACT FROM AUTHOR]

Molecular imaging aims to depict the molecules in living patients. However, because this aim is still far beyond reach, patchworks of different solutions need to be used to tackle this overarching goal. From the vast toolbox of imaging techniques, we focus on those recent advances in optical microscopy that image molecules and cells at the submicron to centimeter scale. Mesoscopic imaging covers the "imaging gap" between techniques such as confocal microscopy and magnetic resonance imagingthat image entire live samples but with limited resolution. Microscopy focuses on the cellular level; mesoscopy visualizes the organization of molecules and cells into tissues and organs. The correlation between these techniques allows us to combine disciplines ranging from whole body imaging to basic research of model systems. We review current developments focused on improving microscopic and mesoscopic imaging technologies and on hardware and software that push the current sensitivity and resolution boundaries. [ABSTRACT FROM AUTHOR]

• Labeling strategies for N-glycans are reviewed. • Labeling strategies are discussed based on both liquid chromatography and capillary electrophoresis separation methods. • The choice of labelings is based on both fluorescence and mass spectrometry detection methods. • Advantages and disadvantages of labeling agents are discussed. • Advanced labelings based on multiplex agents for a quantitative approach are discussed. This mini review summarizes the current methods used for screening N- glycosylation of glycoproteins, with a specific focus on therapeutic proteins and on techniques involving the release of N- glycans. With the continuous development of biopharmaceuticals, particularly monoclonal antibodies (mAbs), which are N- glycosylated proteins, monitoring has gained importance in recent decades. Glycosylation of therapeutic glycoproteins is considered a critical quality attribute because it can impact the efficacy and safety of these therapeutic drugs. The protocols and instrumentation have evolved with the advancement of technologies. Nowadays, methods are becoming increasingly robust, rapid, and sensitive. For the release of N- glycans, the most commonly used method is enzymatic release using PNGase F. The latter is discussed in light of the advent of rapid release that is now possible. The strategy for separating N- glycans using either liquid chromatography (LC) with hydrophilic interaction liquid chromatography (HILIC) chemistry or capillary electrophoresis will be discussed. The selection of the labeling agent is a crucial step in sample preparation for the analysis of released N- glycans. This review also discusses labeling agents that are compatible with and dependent on the separation and detection techniques employed. The emergence of multiplex labeling agents is also summarized. The latter enables the analysis of multiple samples in a single run, but it requires MS analysis. [ABSTRACT FROM AUTHOR]

• Graphic yellow warnings with images that reflect concrete consequences are the most effective to communicate the risks of cannabis use. • Graphic yellow warnings diminish product appeal, increases harm perception, discourages intention to try them and grab attention. • The most effective themes were mental health, smoke toxicity, aesthetic implications and driving high. Health warning label on cannabis products has been recently studied, and with the latest trends of regulation around the world, there is a need to determine the most effective ways to apply this strategy. The current study aimed to examine the effects of different health warning label designs (pictorial vs text-only, background color, warning themes) on cannabis products. An online experiment study (N =533) was carried out in Colombia with a between-subject design. Participants were randomly assigned to five package conditions: without warning, text-only white warning, text-only yellow warning, pictorial white warning, and pictorial yellow warning. Participants performed an attention task and rated each of the stimuli based on product appeal, perceived addictiveness, harm perception, and interest in trying cannabis products. Pictorial health warnings were generally the most effective. Especially, pictorial health warnings with a yellow background were found to decrease product appeal and interest in trying cannabis products, as well as increase harm perception compared to other designs. The most effective warning themes were mental health, smoke toxicity, aesthetic implications, and traffic accidents. The current study provides empirical evidence on the effectiveness of different designs of cannabis health warnings. Our results suggest that graphic yellow warnings are the most effective in communicating the risks of cannabis use. [ABSTRACT FROM AUTHOR]

• Peer labeling challenges the idea that labeling is only done by those in power. • Labels assigned to students can influence their behavior, acting as self-fulfilling prophecies. • Social differences such as gender and age lead to the formation of cognitive classifications that manifest as labels. • Labels shape students' motivation and behavior strongly influencing their social identities. The purpose of this study is to comprehensively investigate the labeling phenomenon within high schools, considering the perspectives of school administrators, teachers, and students. The research employed a multiple-nested case design, focusing on two distinct school cases characterized by differences in student recruitment, teacher composition, and administrative staff. Participants were selected using a purposive sampling method, and data collection involved conducting semi-structured interviews with eight students, twelve teachers, and four school administrators. The data analysis proceeded in two stages: first, an independent analysis of each case, followed by cross-case analyses and comparisons between the cases. The findings of this research illuminate several key points. Firstly, labeling is prevalent among individuals within the school environment. Secondly, labels are formulated based on socially distinctive characteristics, which manifest within the organizational context. Lastly, labels applied to students possess the potential to trigger self-fulfilling prophecies. [ABSTRACT FROM AUTHOR]

Molecular imaging is a non-invasive process that enables the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro / in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77). [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed nanovesicles. EVs are emerging as keys for identifying molecular mechanisms by mediating intercellular communication. EVs allow the exchange of various components with neighboring and distant cells through the extracellular environment, thereby involving in various biological processes in both physiological and pathological conditions such as wound healing, immune response, and tumorigenesis. EVs are also growing rapidly as cargo carrier for their natural delivery properties. Development of bioinspired delivery nanoplatforms based on exosomes-like mimetics also showed potentials to overcome limitations of synthetic nanoparticles. EVs offer a window to multicomponent diagnosis and a tool for design therapeutics. However, for successful clinical translation of EVs, the understanding of in vivo behavior is essential. Advancements in molecular imaging enabled high-resolution in vivo tracking of EVs, providing valuable information regarding trafficking, biodistribution, cellular uptake and molecular mechanism of EVs. Recent studies have explored various methods for visualizing EVs, each imaging technique has certain strengths and limitations. Highly specific, sensitive and biocompatible labeling and tracking strategies still in demand in EV visualization. In this review, we summarized methods for labeling and tracking of EVs and discussed benefits and drawbacks for each method. Future novel imaging modalities and combined strategies will provide avenues for understanding EV behavior and accelerate their clinical translation. Unlabelled Image • Extracellular vesicles (EVs) are interesting therapeutic tools but their in vivo behavior has not been fully understood. • Commonly methods used for visualization of EVs were comprehaneively summareized and compared. • Strategies such as photoacoustic imaging and Raman spectroscopy are emerging for labeling and tracking of EVs. • Powerful molecular imaging strategies would accelerate clinical translation of EVs-based therapy. [ABSTRACT FROM AUTHOR]

A k - L (p , q) -labeling of a graph G is a function ϕ : V (G) → { 0 , 1 , ... , k } such that | ϕ (x) − ϕ (y) | ≥ p if x and y are adjacent and | ϕ (x) − ϕ (y) | ≥ q if x and y are of distance two apart. The L (p , q) -labeling number of G , denoted by λ p , q (G) is the least k for which G has a k - L (p , q) -labeling. Let p ≥ q ≥ 1 be integers and let g be the girth of a graph G. In this paper we prove that (1) if G is a planar graph with g ≥ 5 , then λ p , q (G) ≤ (2 q − 1) Δ + 6 p + 10 q − 8. (2) Let G be a planar graph with g ≥ 6. There exists an integer Δ 0 (p , q) such that λ p , q (G) ≤ q Δ + 2 p + q − 2 if Δ ≥ Δ 0 (p , q). Our results partially generalize some known results and the second result is best possible for the case p = q = 1. [ABSTRACT FROM AUTHOR]

Negative symptoms in schizophrenia show striking similarities to some depressive symptoms. Different terms are often used for these phenomenologically similar symptoms depending on the context, such as avolition (most often used in the context of schizophrenia) and lack of drive (most often used in the context of depression). To test whether clinicians assign different symptom labels to the same clinical picture based on the cued diagnosis, 98 clinical psychologists and psychiatrists were presented with two case studies that were randomly framed as characterizing an individual with either depression or schizophrenia. An interaction of the symptom label group selected by the clinicians with the framing condition confirmed our hypothesis: despite identical content, clinicians favored different clinical terms depending on the cued diagnosis (p = .025, η2partial = 0.054). This result was supported by the suspected diagnosis suggested by the clinicians; numerically, they more often confirmed than rejected the cued diagnosis. The present study is in line with earlier findings indicative of strong overlap pertaining to the phenomenology of negative symptoms in schizophrenia and depressive symptoms that suggest that clinical terminology should be streamlined. The hypothesis that core symptoms of both syndromes tap largely the same construct should be further pursued. If true, the concept of negative symptoms, currently used to describe schizophrenia alone, should be opened up for describing symptoms in other disorders. This could help to gain a deeper understanding of the transdiagnostic appearances of the negative syndrome. [ABSTRACT FROM AUTHOR]

DNA aptamers were selected for their ability to bind specifically and quickly to crystalline hydroxyapatite (Ca 10 (PO 4) 6 (OH) 2 ; HAP), the primary mineral component of enamel and bone. Aptamers were found to have an enhanced percent of G-nucleotides and a propensity for forming a G-quadruplex secondary structure. One aptamer was studied in comparison to control sequences and was found to bind with high affinity and at high loading capacity, with enhanced binding kinetics, and with specificity for crystalline HAP material over amorphous calcium phosphate (ACP) and β-tricalcium phosphate (TCP). The fluorescently-functionalized aptamer was demonstrated to specifically label HAP in a surface binding experiment and suggests the usefulness of this selected aptamer in biomedical or biotechnology fields where the labeling of specific calcium phosphate materials is required. Image 1 • SELEX carried out for aptamer binding to hydroxyapatite surface. • DNA aptamer identified with enhanced kinetics and selectivity. • Selective labeling of crystalline calcium phosphate over amorphous material. • Utility as affinity reagent in microscopy studies of mineral materials. [ABSTRACT FROM AUTHOR]

Purpose: Ways of labeling a person with epilepsy (PWE) may have an impact on public position towards affected persons. This study analyzed college students position changes, influenced by three different labels of PWE.Methods: Observational, descriptive, cross-sectional study. Students of three schools answered one of three questionnaires whose content changed in the labeling form: person with epilepsy, epileptic or PWE. Proportions were compared with Chi square test or Fisher's exact test to explore considering age, gender, religion practicing, socioeconomic status, knowing an affected person and by faculty.Results: A total of 273 questionnaires were included were distributed in medicine 133 (48.7 %), engineering 108 (39.6 %) and law 32 (11.7 %) schools. Labeling type distribution was person with epilepsy 94 (34.4 %), epileptic 93 (34.1 %) and PWE 86 (31.5 %. No statistical differences were found according the labels person with epilepsy and epileptic. The abbreviation PWE had statistical significant connotation in aspects of academic achievement p = 0,007, selecting a PWE in your work team p = 0,009, self control p < 0,000, being dangerous p < 0,000 and having any disturbance in thought or behavior p = 0,05. Religion practicing, socioeconomic status and knowing a person with epilepsy did not impact in attitude related to labeling. Engineering and law students expressed their concern in employability.Conclusion: The abbreviation PWE may have negative connotations when used in written questionnaires. No differences were found with the labels person with epilepsy and epileptic in college students. More studies are needed to explore the stigmatizing or destigmatizing effects of labeling a person with epilepsy on different populations. [ABSTRACT FROM AUTHOR]

Radionuclide-based imaging of molecular therapeutic targets might facilitate stratifying patients for specific biotherapeutics. New type of imaging probes, based on designed ankyrin repeat proteins (DARPins), have demonstrated excellent contrast of imaging of human epidermal growth factor type 2 (HER2) expression in preclinical models. We hypothesized that labeling approaches, which result in lipophilic radiometabolites (non-residualizing labels), would provide the best imaging contrast for DARPins that internalize slowly after binding to cancer cells. The hypothesis was tested using DARPin Ec1 that binds to epithelial cell adhesion molecule (EpCAM). EpCAM is a promising therapeutic target. Ec1 was labeled with 125I using two methods to obtain the non-residualizing labels, while residualizing labels were obtained by labeling it with 99mTc. All labeled Ec1 variants preserved target specificity and picomolar binding affinity to EpCAM-expressing pancreatic adenocarcinoma BxPC-3 cells. In murine models, all the variants provided similar tumor uptake. However, 125I-PIB-H 6 -Ec1 had noticeably lower retention in normal tissues, which provided appreciably higher tumor-to-organ ratios. Furthermore, 125I-PIB-H 6 -Ec1 demonstrated the highest imaging contrast in preclinical models than any other EpCAM-imaging agent tested so far. In conclusion, DARPin Ec1 in combination with a non-residualizing label is a promising probe for imaging EpCAM expression a few hours after injection. • Labeled designed ankyrin repeat proteins (DARPins) are new type of imaging probes. • Influence of radiolabeling strategy on DARPins biodistribution was investigated. • Labeling strategy influences retention of radiometabolites in normal tissues. • Optimal labeling dramatically improves contrast of DARPin-mediated imaging. • Non-residualizing labels are preferable for slowly internalizing DARPins. [ABSTRACT FROM AUTHOR]

In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS). The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure. The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label. The synthesized labels were characterized by NMR, IR, UV/Vis, fluorescence spectroscopy and mass spectrometry. Furthermore, the labels were applied for maltooligosaccharide standards as well as N -linked glycans labeling via reductive amination and followed by CE-MS analysis. The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals. Image 1 • New multi-cationic aminopyrene-based labeling tags were designed and synthesized. • The synthesized labels were characterized by NMR, IR, UV/Vis, fluorescence spectroscopy, and mass spectrometry. • The labels were successfully applied for maltooligosaccharides and N -linked glycans labeling followed by CE-MS analysis. [ABSTRACT FROM AUTHOR]

We have developed a nuclear and fluorescence labeling strategy for nanocrystalline cellulose (CNC), an emerging biomaterial with versatile chemistry and facile preparation from renewable sources. We modified CNC through 1,1′-carbonyldiimidazole (CDI) activation with radiometal chelators desferrioxamine B and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), allowing for the labeling with zirconium-89 (t ½ = 78.41 h) and copper-64 (t ½ = 12.70 h), respectively, for non-invasive positron emission tomography (PET) imaging. The far-red fluorescent dye Cy5 was added for ex vivo optical imaging, microscopy and flow cytometry. The multimodal CNC were evaluated in the syngeneic orthotopic 4T1 tumor model of human stage IV breast cancer. Modified CNC exhibited low cytotoxicity in RAW 264.7 macrophages over 96 h, and high radiolabel stability in vitro. After systemic administration, radiolabeled CNC were rapidly sequestered to the organs of the reticulo-endothelial system (RES), indicating immune recognition and no passive tumor targeting by the enhanced permeability and retention (EPR) effect. Modification with NOTA was a more favorable strategy in terms of radiolabeling yield, specific radioactivity, and both the radiolabel and dispersion stability in physiological conditions. Flow cytometry analysis of Cy5-positive immune cells from the spleen and tumor corroborated the uptake of CNC to phagocytic cells. Future studies on the in vivo behavior of CNC should be concentrated on improving the nanomaterial stability and circulation half-life under physiological conditions and optimizing further the labeling yields for the multimodality imaging strategy presented. Our studies constitute one of the first accounts of a multimodality nuclear and fluorescent probe for the evaluation of CNC biodistribution in vivo and outline the pitfalls in radiometal labeling strategies for future evaluation of targeted CNC-based drug delivery systems. Quantitative and sensitive molecular imaging methods provide information on the structure–activity relationships of the nanomaterial and guide the translation from in vitro models to clinically relevant animal models. [ABSTRACT FROM AUTHOR]

Polysaccharides are ubiquitous, generally benign in nature, and compatible with many tissues in biomedical situations, making them appealing candidates for new materials such as therapeutic agents and sensors. Fluorescent labeling can create the ability to sensitively monitor distribution and transport of polysaccharide-based materials, which can for example further illuminate drug-delivery mechanisms and therefore improve design of delivery systems. Herein, we review fluorophore selection and ways of appending polysaccharides, utility of the product fluorescent polysaccharides as new smart materials, and their stimulus-responsive nature, with focus on their biomedical applications as environment-sensitive biosensors, imaging, and as molecular rulers. Further, we discuss the advantages and disadvantages of these methods, and future prospects for creation and use of these self-reporting materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Glycosylation analysis is still challenging, not only because of the extreme structure complexity and conjugation diversity of glycans but also because of instrumental aspects such as the sensitivity limits of analyses. Therefore, glycan analysis by chromatographic methods is very often combined with fluorescence detection in addition to MS. The majority of fluorescent labeling employed before LC separation is based on 2-aminobenzamide, which has several disadvantages such as low labeling yield, poor fluorescence properties, and MS ionization efficiency. Therefore, even after several decades of development of new labels, there is still a need for new labeling tags with improved characteristics. We present the application of a newly synthesized fluorescent label designed for oligosaccharide and glycan analysis by high-performance liquid chromatography with fluorescence detection (HPLC/FLD). The novel hydrazide derivative of dipyrrometheneboron difluoride (BODIPY) was synthesized from 2,4-dimethylpyrrole, methyl succinyl chloride, and boron trifluoride etherate followed by a reaction with hydrazine. The synthesized label was characterized by several analytical methods including NMR, UV/Vis and fluorescence spectroscopy, and mass spectrometry. The labeling reaction via hydrazone formation chemistry was optimized by labeling of maltooligosaccharide standards. The analysis of maltohexaose labeled by BODIPY-hydrazide followed by HPLC/FLD analysis provided the limit of detection in the low tens of femtomole. The presented method based on fluorescence detection is at least 30 times more sensitive than the standard approach employing labeling by 2-aminobenzamide. In addition, the labeling method by BODIPY-hydrazide was used for N-linked glycan profiling of several glycoproteins (ribonuclease B, immunoglobulin G) by RP-HPLC/FLD as well as HILIC/FLD analysis. This work represents the design, synthesis, and application of a new fluorescent label based on the BODIPY core and hydrazone formation chemistry for oligosaccharide and glycan analysis by HPLC/FLD. The proposed approach significantly improved the oligosaccharide and glycan analysis in comparison to the commonly used procedure employing 2-aminobenzamide. [Display omitted] • A new fluorescent BODIPY-based tag was synthesized for glycan analysis by HPLC. • The label was characterized by NMR, UV/Vis, fluorescence spectroscopy, and MS. • The labeling conditions were optimized using maltooligosaccharide standards. • The BODIPY-based tag was compared to the standard label, 2-aminobenzamide. • The BODIPY-based tag was applied for N-linked glycan profiling by HPLC/FLD-MS. [ABSTRACT FROM AUTHOR]

An antimagic labeling of a digraph D with n vertices and m arcs is a bijection from the set of arcs of D to { 1 , 2 , ... , m } such that all n oriented vertex-sums are pairwise distinct, where the oriented vertex-sum of a vertex is the sum of labels of all arcs entering that vertex minus the sum of labels of all arcs leaving it. A graph G admits an antimagic orientation if G has an orientation D such that D has an antimagic labeling. Hefetz, Mütze and Schwartz conjectured every connected graph admits an antimagic orientation. In this paper, we support this conjecture by proving that any forest obtained from a given forest with at most one isolated vertex by subdividing each edge at least once admits an antimagic orientation. [ABSTRACT FROM AUTHOR]

An antimagic labeling of a digraph D with n vertices and m arcs is a bijection from the set of arcs of D to { 1 , 2 , ... , m } such that all n oriented vertex sums are pairwise distinct, where an oriented vertex sum of a vertex is the sum of labels of all arcs entering that vertex minus the sum of labels of all arcs leaving it. Hefetz, Mütze and Schwartz conjectured every connected undirected graph admits an antimagic orientation. In this paper, we support this conjecture by proving that every Halin graph admits an antimagic orientation. [ABSTRACT FROM AUTHOR]

The spillover effect in the environmental realm has attracted attention from many researchers. The present study took electricity saving as an example to explore the mechanism of the spillover effect under environmental framing (EF) or monetary framing (MF) and examine the effect of "labeling" on the spillover effect to add value to existing environmental research. Three studies showed that both environmental and monetary framing could promote environmental intention. Study 1 tested the effectiveness of the intervention materials and found that both EF and MF increased the intention to save electricity. Study 2 and 3 revealed that the spillover effect was influenced by framing. Specifically, the spillover of EF was positive, whereas that of MF was negative. At the same time, environmental self-identity mediated both positive and negative spillover. Moreover, enhancing individuals' environmental self-identity by labeling them as "environmentalists" could prevent negative spillover and increase positive spillover. The results of the present study also provided practical guidance regarding pro-environmental education and campaigns by emphasizing environmental benefits rather than monetary benefits and by strengthening environmental self-identity through labeling. • Both environmental and monetary framing promoted environmental behavioral intention. • The spillover effect was influenced by the two different framings. • Environmental self-identity had a mediating effect on spillover. • Labeling someone as an environmentalist could enhance environmental self-identity. • Enhancing environmental self-identity could help avoid negative spillover. [ABSTRACT FROM AUTHOR]

Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labeling of SHVs rendering the comparison of different valves difficult. To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS–STS–AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO), and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labeling of SHV size, in vivo and in vitro testing, and reporting of SHV hemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard- setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS–STS–AATS Valve Labelling Task Force summarizes the background of SHV sizing and labeling and identifies the most important elements where further standardization is necessary. [ABSTRACT FROM AUTHOR]

Consumers are increasingly demanding transparency in food labeling as they want more and better information about what they are eating and where their food comes from. This seems to be particularly the case for food naturalness. Several food indexes or metrics have been developed in the last decades to objectively measure various aspects of food, yet a comprehensive index that quantifies the naturalness of foods is still missing. In the absence of clear rules to define and measure food naturalness, this article describes the development of the Food Naturalness Index (FNI), which aims to accurately measure the degree of food naturalness. The FNI simultaneously integrates and builds on insights from consumer research, legal and technical perspectives. A preliminary assessment of the index with consumers across a wide variety of products was conducted. Key Findings and Conclusions : The FNI proposed herein is comprised of four component measures, namely farming practices, free from additives, free from unexpected ingredients, and degree of processing, which includes 10 relevant food naturalness attributes that can be consistently evaluated from information on the product label. The FNI scores were highly correlated with consumers' perceptions of food naturalness. The FNI has the potential to become a valuable tool in the process of reformulating existing products, developing new ones, and understanding, tracking, and communicating food naturalness attributes in the marketplace. Furthermore, the FNI may provide an objective basis for the use of the "natural" label on food products, which can ultimately lead to better-informed choices. • An objective index that quantifies naturalness of foods is missing. • A comprehensive index to measure food naturalness (FNI) is proposed. • The FNI is based on insights from consumer, legal, and technical perspectives. • The FNI aligns with consumers' perceptions of food naturalness. • The FNI can potentially be used by policy makers, consumers and the food industry [ABSTRACT FROM AUTHOR]

Objectives: In recent years, there has been increasing recognition of the need to assess treatment benefit from the patient's perspective. The extent of patient-reported outcome (PRO) data included in labeling for rare disease treatment is largely unknown. The objective of this study was to review trends over time for PRO-based labeling granted by the US Food and Drug Administration (FDA) for orphan drugs.Study Design: Review of FDA package inserts.Methods: Products included in this analysis were all new molecular entities (NMEs) and biologic license applications (BLAs) with orphan designations approved by the FDA from 2002 through 2017. For identified products, package inserts were reviewed to determine the number and type of PRO claim(s) granted, endpoint status, and PRO measure named. Two trends were analyzed: (1) over all years 2002 to 2017 and (2) 2002 to 2017 stratified into 3 periods (before draft FDA PRO guidance [2006], between draft and final guidance release, and after final guidance [2009] release.Results: A total of 156 NMEs and BLAs with orphan designations were approved between 2002 and 2017. Of these, 13 products (8.3%) had PRO-based labeling, and 7 of 13 were symptom-related. The percent of orphan drugs approved with PRO-based labeling between 2002 and 2005, 2006 and 2008, and 2009 and 2017 was 0, 10.5, and 9.9, respectively.Conclusions: In FDA-approved labeling for orphan therapies, PRO measures used as primary and secondary endpoints increased after draft FDA PRO guidance release but remained relatively low thereafter. It is important to understand barriers to PRO measure use to ensure that treatments capture perspectives of patients with rare diseases. [ABSTRACT FROM AUTHOR]

Highlights • RNA interference (RNAi) technology boasts potential cost-saving benefits if adopted in livestock production. • We estimate consumers' WTP for beef steaks with varying RNAi use, antibiotic use and USDA grade attributes. • We find consumers require a discount for beef products with RNAi use attributes. • Varying label wording of product attributes we simulate consumer demand under potential governmental regulations. Abstract This study estimates, for the first time in the meat sector, consumer willingness to pay (WTP) for genetically modified foods produced using RNA interference (RNAi), a new gene editing technology. We examine WTP in four different choice experiment designs involving beef steaks with varying number of attributes, label setting and label wording to assess consumer demand. Results suggests consumers will require a discount for beef products produced using RNAi, with specific magnitudes varying substantially based upon the labeling wording faced by consumers. Therefore, ultimate RNAi adoption will reflect the magnitude of inner-supply chain, cost reductions given consumer demand. [ABSTRACT FROM AUTHOR]

The Systolic Blood Pressure Intervention Trial (SPRINT) compared the clinical outcomes between target systolic blood pressure (SBP) levels between 140 and 120 mmHg or lower. Both,the 2017 ACC/AHA and the 2018 ESC/ESH guidelines in hypertension are derived from the SPRINT trial and advise initiation and/or intensification of treatment at lower blood pressure thresholds. The ACC/AHA guidance supersedes the 2014 Eight Joint National Committee guideline (JNC-8) which advised initiation of treatment when the BP was 140/90 mmHg or higher; in adults 60 years or over, the target was 150/90 mmHg. Compared to JNC-8, the new guidelines lower the SBP target by 10 mmHg in patients under age of 60 years, and by 20 mmHg in the elderly. We performed a qualitative multi-dimensional analysis in order to answer two key questions: will the new guidelines deliver the stated benefits? and, will translation to the clinic be simple, risk-free, and affordable? A major investment by national healthcare administrations will be necessary for the initiation and support of this program but this decision can only be justified by a valid expectation of clinical benefit. At this time, a definitive answer is not available and a "wait and see" attitude appears appropriate and reasonable. In the interim, efforts are best directed to the immediate problem of untreated hypertension worldwide. [ABSTRACT FROM AUTHOR]

• The Who-Said-What-task can measure implicit mental illness based categorization. • Implicit categorization is found for the labels schizophrenia and depression. • Small associations with explicit stigmatization were found. Several models that attempt to explain stigmatization of people with mental illness emphasize the relevance of social categorization. However, research on illness-based social categories has been limited to explicit self-report measures. In this study, we explored whether implicit social categorization based on mental illness labels can be assessed with the "Who-Said-What" (WSW)-paradigm. In this paradigm, participants have to allocate a large number of statements to individuals who belong to different social groups (e.g., mentally ill vs. healthy). Due to the amount of statements, errors in allocation are to be expected. A disproportionate amount of erroneous allocation to individuals within a social group is interpreted to indicate implicit social categorization. In three studies, we (1) pilot-tested a WSW-paradigm for mental illness categorization (n = 24), (2) replicated these findings in an independent, larger sample (n = 85), and (3) aimed to rule out alternative explanations for the implicit categorization effects with a modified WSW-task and novel stimulus material (n = 137). We found consistent implicit categorization effects with overall medium to large effect sizes (range: 0.41 ≤ d ≤ 1.01). Implicit components of mental illness based social categorization can be assessed with the WSW-paradigm. Future research needs to explore the interrelations of implicit categorization, implicit vs. explicit stigmatization and discriminating behavior. [ABSTRACT FROM AUTHOR]

Abstract Filamentous bacteria, particularly Microthrix parvicella , are mainly responsible for bulking or foaming of activated sludge. Based on the affinity of M. parvicella to the hydrophobic characteristics of long-chain fatty acids, a novel bisoctyl rhodamine B (BORB) and a novel fluorescence resonance energy transfer (FRET) complex probe were prepared herein to study their properties. When the FRET probe was used in in situ activated sludge, M. parvicella was clearly labeled at 20 nmol/L, which was a reduction of 50 times compared to that of the BORB (1 μmol/L) alone and 500 times compared to the carbazole–quinoline probe reported previously. Compared with fluorescence in situ hybridization, M. parvicella could be clearly labeled using BORB and the FRET probe in situ without requiring complicated pretreatments (i.e., shock and broken process, fixed sample, digestion, and lysozyme treatment). This study discusses the facile approach developed for labeling M. parvicella in early warning expansion, thereby inhibiting and controlling sludge bulking in situ. Graphical abstracts FRET process between BORB and QDs, and images of labeling for M. parvicella. Unlabelled Image Highlights • A novel bisoctyl Rhodamine B for labeling M. parvicella was synthesized. • A novel FRET probe labeling for M. parvicella was prepared. • The labeling procession occurred in situ without broken or lysozyme pretreatment. • It provides an potential method for warning expansion in activated sludge bulking in situ. [ABSTRACT FROM AUTHOR]

Most commercially available fluorescent dyes used for cellular images are toxic and their luminescence is often outshined by the intrinsic autofluorescence of the biological medium, the use of long emission lifetime inherent of the lanthanide compounds is a viable alternative. This paper reports the development of a luminescent hybrid based on silica nanoparticles decorated with Tb3+ complexes suitable for use in exploratory tests as biomarkers in the visualization of CHO-k1 cells by microscopy techniques. To achieve this aim, spherical/spheroidal (∼125 nm) functionalized silica particles were prepared by the sol-gel method and had their surface functionalized covalently with Schiff base ligands. Tb3+ Complexes were bonded onto the particles surface by a step-by-step methodology approach. By zeta potential, it was possible to investigate the particles surface charge after each synthesis step, reaching a negative value for the final hybrid, which showed intense luminescence in the green region, where the Tb3+5D 4 → 7F J transitions were observed in the emission spectrum. After the benzoic acid ligand (BzAc) addition, there was an intensification of Tb3+ emission, as well as an increase in the emission lifetime. Concerning the biological application of the material, the CHO-k1 cell viability was evaluated by the MTT method in the presence of the SiO 2 -[Tb(SB)(BzAc) y ] hybrid, and high biocompatibility was observed. The absorption process of particles by the cells was investigated by TEM, suggesting an endocytosis mechanism as a probable uptake process. The confocal images indicated a green emission of the biomarker due to the Tb3+, distributed through the cytoplasm, mainly closely to the cell nuclei. Therefore, the silica particles decorated with Tb3+ complexes proved to be suitable to act as biomarkers in biological assays and cellular imaging. • Step-by-step approach to decorate silica with Tb3+-complexes obtained via sol-gel. • Schiff base and benzoic acid ligands as sensitizers for Tb3+ ions. • Intense Tb3+ green emission. • Longer lifetime emission of the Tb3+-complexes after anchoring to the silica matrix. • Endocytosis mechanism for particles uptake process by CHO-k1 cells. [ABSTRACT FROM AUTHOR]

Highlights • Surface contamination caused by handling nanomaterials was traced using fluorescently labeled 80-nm silica nanoparticles. • Fluorescent silica nanoparticles granted high analytical sensibility, small sizes and high dispersability in aerosol phase. • Below 100 ppm of fluorescent nanoparticles added to the aerosol matter allowed exposure assessment in wide contact surfaces. • The appropriate illumination revealed the deposition zones, allowing a low-cost procedure for risk assessment tests. Abstract The deposition of airborne nanosized matter onto surfaces could pose a potential risk in occupational and environmental scenarios. The incorporation of fluorescent labels, namely fluorescein isotiocyanate (FITC) or tris-1,3-phenanthroline ruthenium (II) chloride (Ru(phen) 3 Cl 2), into spherical 80-nm silica nanoparticles allowed the detection after the illumination with LED light of suitable wavelength (365 or 405 nm respectively). Monodisperse nanoparticle aerosols from fluorescently labeled nanoparticles were produced under safe conditions using powder generators and the deposition was tested into different surfaces and filtering media. The contamination of gloves and work surfaces that was demonstrated by sampling and SEM analysis becomes immediately clear under laser or LED illumination. Furthermore, nanoparticle aerosols of about 105 nanoparticles/cm3 were alternatively fed through a glass pipe and personal protective masks to identify the presence of trapped nanoparticles under 405 nm or 365 nm LED light. This testing procedure allowed a fast and reliable estimation of the contamination of surfaces with nanosized matter, with a limit of detection based on the fluorescence emission of the accumulated solid nanoparticles of 40 ng of Ru(phen) 3 @SiO 2 of silica per mg of non-fluorescent matter. [ABSTRACT FROM AUTHOR]

Objectives: To compare US Food and Drug Administration (FDA) and European Medicines Agency (EMA) labeling for evidence based on patient-reported outcomes (PROs) of new oncology treatments approved by both agencies.Methods: Oncology drugs and indications approved between 2012 and 2016 by both the FDA and the EMA were identified. PRO-related language and analysis reported in US product labels and drug approval packages and EMA summaries of product characteristics were compared for each indication.Results: In total, 49 oncology drugs were approved for a total of 64 indications. Of the 64 indications, 45 (70.3%) included PRO data in either regulatory submission. No FDA PRO labeling was identified. PRO language was included in the summary of product characteristics for 21 (46.7%) of 45 indications. European Organisation for Research and Treatment of Cancer and Functional Assessment of Cancer Therapy measures were used frequently in submissions. FDA's comments suggest that aspects of study design (eg, open labels) or the validity of PRO measures was the primary reason for the lack of labeling based on PRO endpoints. Both agencies identified missing PRO data as problematic for interpretation.Conclusions: During this time period, the FDA and the EMA used different evidentiary standards to assess PRO data from oncology studies, with the EMA more likely to accept data from open-label studies and broad concepts such as health-related quality of life. An understanding of the key differences between the agencies may guide sponsor PRO strategy when pursuing labeling. Patient-focused proximal concepts are more likely than distal concepts to receive positive reviews. [ABSTRACT FROM AUTHOR]

Highlights • Perception and WTP changes from a minimal information label were measured. • Belief the product was local increased despite no new information on origin. • Safety impressions increased without any safety information on the label. • Adding an additional label continued to increase these perceptions and WTP. • Labels appear able to change perceptions beyond the information they contain. Abstract With more labels appearing on food products, it becomes questionable how many add relevant information to consumers. Some products have labels conveying no, redundant, or minimal information, while others have multiple labels that contain overlapping information. The expansion of these types of minimal-information labeling suggests a perception among marketers that labels improve consumers’ perceptions and increase willingness to pay (WTP). Using watermelons, field experiments with 328 participants were conducted to estimate WTP differences between (1) a product with a minimal-information label and no label; and (2) a product with a minimal-information label with and without an overlapping label. While the minimal-information label added nothing new about the origin of the watermelon (redundant information), added minimal information on taste, and provided no mention of food safety (no information), perceptions among participants of all these attributes positively and significantly increased in both label comparisons. The WTP for the product with a minimal-information label also increased, demonstrating consumers will sacrifice real money for products with these labels. The evidence suggests that labels have capabilities to shape perceptions and influence WTP even beyond those attributes they make a claim regarding. [ABSTRACT FROM AUTHOR]