Bridging instrumental and visual perception with improved color difference equations: A multi-center study.

OBJECTIVES: This multicenter study aimed to evaluate visual-instrumental agreement of six color measurement devices and optimize three color difference equations using a dataset of visual color differences (∆V) from expert observers. METHODS: A total of 154 expert observers from 16 sites across 5 countries participated, providing visual scaling on 26 sample pairs of artificial teeth using magnitude estimation. Three color difference equations (ΔE*ab, ∆E00, and CAM16-UCS) were tested. Optimization of all three equations was performed using device-specific weights, and the standardized residual sum of squares (STRESS) index was used to evaluate visual-instrumental agreement. RESULTS: The ΔE*ab formula exhibited STRESS values from 18 to 40, with visual-instrumental agreement between 60 % and 82 %. The ∆E00 formula showed STRESS values from 26 to 32, representing visual-instrumental agreement of 68 % to 74 %. CAM16-UCS demonstrated STRESS values from 32 - 39, with visual-instrumental agreement between 61-68 %. Following optimization, STRESS values decreased for all three formulas, with ΔE' demonstrating average visual-instrumental agreement of 79 % and ∆E00 of 78 %. CAM16-UCS showed average visual-instrumental agreement of 76 % post optimization. SIGNIFICANCE: Optimization of color difference equations notably improved visual-instrumental agreement, overshadowing device performance. The optimzed ΔE' formula demonstrated the best overall performance combining computational simplicty with outstanding visual-instrumental agreement.

DNA Meets Protein─Development, Characterization, and Application of Aptamers against Peanut Allergen.

Allergen detection methods support food labeling and quality assessment at the allergen component level of allergen preparations used for allergy diagnosis and immunotherapy (AIT). Commonly applied enzyme-linked immunosorbent assay (ELISA) requires animal antibodies but potentially shows batch variations. We developed synthetic aptamers as alternative binders in allergen detection to meet the replacement, reduction, and refinement (3R) principle on animal protection in science. ssDNA aptamers were specifically selected against the major peanut allergen Ara h 1 and identified by next-generation sequencing. Application in various detection systems (ELISA-like assays, western blot, and surface plasmon resonance) was demonstrated. The ELISA-like assay comprised a sensitivity of 10 ng/mL Ara h 1, comparable to published antibody-based ELISA, and allowed Ara h 1 detection in various peanut flours, similar to those used in peanut AIT as well as in processed food. This ELISA-like aptamer-based assay proofs antibody-free allergen detection for food labeling or quality assessment of diagnostic and therapeutic allergen products.

Resin infiltration versus fluoride varnish for visual improvement of white spot lesions during multibracket treatment. A randomized-controlled clinical trial.

AIMS: This study aimed to evaluate the visual improvement of resin infiltration of white spot lesions (WSL) during orthodontic treatment with the multibracket appliance (MBA) compared to fluoride varnish. METHODS: Patients aged 12-17 years with at least one WSL with an International Caries Detection and Assessment System (ICDAS) score of 1-2 during an active MBA treatment were included and randomized to receive either resin infiltration (Icon) or fluoride application (Flairesse). Standardized digital images were obtained before, one-day, one-week, one-month, three-months and six-months after treatment using a DSLR camera and a matching polarization filter. A grey reference card was used for color standardization. A Matlab routine was used to measure the color difference between adjacent healthy enamel and treated WSL. The independent-samples t-test was used for intergroup and paired-samples t-test for intragroup comparison. RESULTS: Images of 116 teeth from 36 patients were analyzed. The ΔE for the "Icon" treated WSL was smaller (T1ICON = 5.0 ± 1.4) than in the fluoride group (T1Fluoride = 8.4 ± 3.2). Caries infiltration significantly improved the aesthetic appearance of WSL (p < 0.001), which remained satisfactory at six months (T5ICON = 5.2 ± 1.6). CONCLUSION: WSL infiltration management during orthodontic treatment was superior to topical fluoridation in not only arresting the enamel lesions but also significantly improving the aesthetic appearance of demineralized regions around the brackets. CLINICAL RELEVANCE: WSL treatment in orthodontic patients is usually initiated after debonding. Research has shown that the earlier WSL is treated, the better the aesthetic outcome. There is limited data on the efficacy of resin infiltration of WSL during orthodontic treatment.

Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow.

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.

Inhibition of Pim kinases triggers a broad antiviral activity by affecting innate immunity and via the PI3K-Akt-mTOR axis the endolysosomal system.

Zoonoses such as ZIKV and SARS-CoV-2 pose a severe risk to global health. There is urgent need for broad antiviral strategies based on host-targets filling gaps between pathogen emergence and availability of therapeutic or preventive strategies. Significant reduction of pathogen titers decreases spread of infections and thereby ensures health systems not being overloaded and public life to continue. Based on previously observed interference with FGFR1/2-signaling dependent impact on interferon stimulated gene (ISG)-expression, we identified Pim kinases as promising druggable cellular target. We therefore focused on analyzing the potential of pan-Pim kinase inhibition to trigger a broad antiviral response. The pan-Pim kinase inhibitor AZD1208 exerted an extraordinarily high antiviral effect against various ZIKV isolates, SARS-CoV-2 and HBV. This was reflected by strong reduction in viral RNA, proteins and released infectious particles. Especially in case of SARS-CoV-2, AZD1208 led to a complete removal of viral traces in cells. Kinome-analysis revealed vast changes in kinase landscape upon AZD1208 treatment, especially for inflammation and the PI3K/Akt-pathway. For ZIKV, a clear correlation between antiviral effect and increase in ISG-expression was observed. Based on a cell culture model with impaired ISG-induction, activation of the PI3K-Akt-mTOR axis, leading to major changes in the endolysosomal equilibrium, was identified as second pillar of the antiviral effect triggered by AZD1208-dependent Pim kinase inhibition, also against HBV. We identified Pim-kinases as cellular target for a broad antiviral activity. The antiviral effect exerted by inhibition of Pim kinases is based on at least two pillars: innate immunity and modulation of the endolysosomal system.

Illuminant metamerism between natural teeth and zirconia restorations evaluated with a chromatic adaptation transform.

STATEMENT OF PROBLEM: Little is known about the effect of illuminant metamerism between natural teeth and zirconia restorations, despite their increasing clinical popularity. PURPOSE: The purpose of this in vitro study was to compare illuminant metamerism between pairs of natural teeth and layered zirconia restorations and pairs of natural teeth and monolithic zirconia restorations under 10 different illuminants and analyze their metameric potential. MATERIAL AND METHODS: Spectral reflectance factors were obtained from 10 pairs of extracted natural teeth and layered zirconia restorations and 28 pairs of extracted natural teeth and monolithic multilayer zirconia restorations. Each pair showed a color match that was within the visual threshold for clinical acceptability (CIEDE2000≤1.8). A special index of metamerism for the change of illuminant (Milm) was calculated from the CIEDE2000 color difference equation. Descriptive statistics and the one-sample t test were used to analyze the results for the Milm and for both groups of layered and monolithic zirconia restorations (α=.05). RESULTS: Layered zirconia restorations reached a mean ±standard deviation value for Milm=0.3 ±0.2 and Milm=0.5 ±0.4 for monolithic zirconia restorations (P<.01). CONCLUSIONS: The effect of illuminant metamerism between natural teeth and zirconia crowns was weak and generally within the clinical acceptability limit.

Assessing Cognitive Skills in Early Childhood Education Using a Bilingual Early Language Learner Assessment Tool.

In this article, we propose that basic cognitive skills may be fostered and assessed in early childhood educational (pre-K) settings using a technology-based approach to assessment. BELLA (Bilingual English Language Learner Assessment), designed for use with both monolingual (English or Spanish speaking) and bilingual (English and Spanish speaking) children, is designed to attend to cognitive skill development in addition to (pre-)academic knowledge. Specifically, BELLA assesses analytical, creative, and practical thinking in 3-5-year-old children through unique item content and delivery. BELLA is among the first tablet-based pre-K assessments designed to assess cognitive skills needed for the era of the Anthropocene.

The fourth vaccination with a non-SARS-CoV-2 variant adapted vaccine fails to increase the breadth of the humoral immune response.

Escape mutations in the spike protein of SARS-CoV-2 are a major reason for Omicron breakthrough infections. After basal vaccination only very low titers of Omicron neutralizing antibodies are present. However, booster vaccinations induce higher titers against the Omicron variant. The neutralization of the Delta and Omicron variants by sera obtained 6 months after 3rd vaccination and 2 weeks or 6 months after 4th vaccination with a monovalent RNA vaccine (Spikevax) was analyzed. It was observed for the Omicron variant that 6 months after the fourth vaccination, the titer returns to the same very low neutralizing capacity as 6 months after the third vaccination. The Delta variant neutralizing capacity wanes with a comparable kinetic although the titers are higher as compared to the Omicron variant. This indicates that the fourth vaccination with a monovalent vaccine based on the ancestral isolate neither affects the kinetic of the waning nor the breadth of the humoral response.

Racial/ethnic disparities of the pact in predicting recidivism and court dispositions for justice-involved youth.

OBJECTIVE: Responding to the concern about racial/ethnic disparities (R/ED) in the use of risk assessment instruments (RAIs) in justice systems, previous research has overwhelmingly tested the extent to which RAI scores consistently predict recidivism across race and ethnicity (predictive bias). However, little is known about R/ED in the association between RAI measures and court dispositions (disparate application) for justice-involved youths. This study investigated predictive bias and disparate application of three risk measures-criminal history, social history, and the overall risk level-produced by the Positive Achievement Change Tool (PACT) for White, Black, and Hispanic justice-involved youths. HYPOTHESES: Given the mixed evidence in existing research for predictive bias and lack of evidence for disparate application, we did not make any specific hypothesis but conducted exploratory analyses. From a clinical perspective, however, we anticipated little or no evidence to support predictive bias and disparate application of the PACT among White, Black, and Hispanic youths in the jurisdiction we examined. METHOD: The sample consisted of 5,578 youths (11.4% White, 43.9% Black, and 44.7% Hispanic) who completed the PACT while in the Harris County Juvenile Probation Department, Texas. The outcome variables included recidivism (general and violent reoffending) and court dispositions (deferred adjudication, probation without placement, and probation with placement). We ran a series of moderating binary logistic regression models and moderating ordinal logistic regression models to evaluate predictive bias and disparate application. RESULTS: Race and ethnicity influenced how the criminal history score related to violent recidivism: This compromised the validity of the score as a predictor of recidivism. Moreover, evidence showed that the overall risk of reoffending was associated with harsher sanctioning decisions for Black and Hispanic youths than for White youths. CONCLUSION: Ensuring that RAI results are consistently interpreted and used in informing decisions is as important as ensuring that RAI scores function equally well in predicting recidivism regardless of race and ethnicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

FcγRIIA-specific DARPins as novel tools in blood cell analysis and platelet aggregation.

Fc receptors are involved in a variety of physiologically and disease-relevant responses. Among them, FcγRIIA (CD32a) is known for its activating functions in pathogen recognition and platelet biology, and, as potential marker of T lymphocytes latently infected with HIV-1. The latter has not been without controversy due to technical challenges complicated by T-B cell conjugates and trogocytosis as well as a lack of antibodies distinguishing between the closely related isoforms of FcγRII. To generate high-affinity binders specific for FcγRIIA, libraries of designed ankyrin repeat proteins (DARPins) were screened for binding to its extracellular domains by ribosomal display. Counterselection against FcγRIIB eliminated binders cross-reacting with both isoforms. The identified DARPins bound FcγRIIA with no detectable binding for FcγRIIB. Their affinities for FcγRIIA were in the low nanomolar range and could be enhanced by cleavage of the His-tag and dimerization. Interestingly, complex formation between DARPin and FcγRIIA followed a two-state reaction model, and discrimination from FcγRIIB was based on a single amino acid residue. In flow cytometry, DARPin F11 detected FcγRIIA+ cells even when they made up less than 1% of the cell population. Image stream analysis of primary human blood cells confirmed that F11 caused dim but reliable cell surface staining of a small subpopulation of T lymphocytes. When incubated with platelets, F11 inhibited their aggregation equally efficient as antibodies unable to discriminate between both FcγRII isoforms. The selected DARPins are unique novel tools for platelet aggregation studies as well as the role of FcγRIIA for the latent HIV-1 reservoir.

Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: results from the COViK study.

PURPOSE: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. METHODS: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. RESULTS: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. CONCLUSION: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

Lace Up and Mindfulness: A Randomized Controlled Trial Intervention to Reduce Emotional Eating, Anxiety, and Sleep Disturbances in Latinx and Black Youth.

This study assessed the effects of a 12-week afterschool mindfulness-based diet and exercise intervention on mental and physical health in Latinx and Black youth. One hundred forty-eight boys and girls (average age = 10.1 years, SD = 1.3 years; 52% girls; 72.3% Latinx) were randomized to either the experimental group (n = 80) or the control group (n = 68). The experimental group participants engaged in fitness yoga, kickboxing, and/or spinning sessions, and mindfulness practices (e.g., breathing, meditation, and mindful eating) twice per week for 12 weeks. The control group participants engaged in a recreational play session once per week for 12 weeks. All participants completed surveys (demographics, acculturation, anxiety, emotional eating, sleep, and food intake) and had their height, weight, and percent body fat measured pre- and post-intervention. Participants wore an accelerometer for 7 days pre- and post-intervention. Repeated measures analysis of covariance indicated that the experimental group participants reported lower scores in emotional eating, anxiety, and sleep latency post-intervention compared to the control group participants. Conversely, no significant differences were observed in physical activity between the experimental and control group participants post-intervention. These findings indicate that a mindfulness-based intervention has a positive effect on emotional eating, anxiety, and sleep latency among youth of color.

Applying Item Response Theory Analysis to the SAVRY in Justice-Involved Youth.

This study investigated item- and test-level functioning of the Structured Assessment of Violence Risk in Youth (SAVRY) and differential item functioning (DIF) across gender and race/ethnicity in justice-involved youth (JIY) using item response theory analysis. Participants were 868 JIY (23.7% female; 26.9% White, 50.9% Black, and 22.2% Hispanic) in pre-trial detention centers in Connecticut. Results obtained from the application of the graded response model showed that the SAVRY items were not equally discriminating JIY with varying levels of the latent trait, with "Poor compliance" as the most discriminating item and "History of self-harm or suicide attempts" as the least discriminating item. At the test level, the SAVRY provided precise (reliable) information about the latent trait for the majority of JIY whose latent trait between two standard deviations below and above the mean. Results of DIF revealed that six items operated inconsistently between White, Black, and Hispanic JIY, among which two items also functioned differentially across gender.

Effectiveness of vaccines in preventing hospitalization due to COVID-19: A multicenter hospital-based case-control study, Germany, June 2021 to January 2022.

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization during the Delta-variant dominance. The two-dose VE was 89 % (95 % CI 84-93 %) overall, 79 % in patients with more than two comorbidities and 77 % in adults aged 60-75 years. A third dose increased the VE to more than 93 % in all patient-subgroups.

Determination of the spectrally resolved extinction coefficient of human dental enamel using collimated transmission spectroscopy.

OBJECTIVES: The determination of the extinction coefficient of human dental enamel to deliver further optical properties of enamel to improve the understanding of light propagation in teeth and to improve restoration materials. METHODS: The extinction coefficient was measured within a spectral range of 300-980 nm using a collimated transmission setup. 35 specimens from 16 donors were examined. The donors were categorized by age and the researched specimen were categorized by tooth type, tooth quality and lateral expansion of the enamel to clarify the influence of these parameters. RESULTS: The obtained spectrally resolved extinction coefficient was accurately described by a power law, which agrees with theoretical scattering models. The results were evaluated with regard to the influence of parameters such as subject age, tooth type, enamel sample quality and enamel width. For this purpose, both the average values of multiple measurements of a single sample in a defined spectral range as well as the curve slope of the averaged results versus wavelength were compared. SIGNIFICANCE: The results provide detailed information about the optical properties of human enamel. The wide spectrum investigated provides important information for the evaluation of the main scatterers and the optical impression under any light condition. However, the deviation of the extinction coefficient varies less between the mean values for the specimens grouped by several parameters than between the specimens themselves within a group. This indicates a unique optical behaviour for every specimen and this requires consideration in the development of artificial materials.

Advancing Precision Vaccinology by Molecular and Genomic Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 in Germany, 2021.

BACKGROUND: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany. METHODS: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI. RESULTS: We report analyses of 3623 SARS-CoV-2 genomes collected between December 2020 and December 2021, of which 3282 were randomly sampled. All variants of concern were identified in the sequenced sample set, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modeled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave. CONCLUSIONS: SARS-CoV-2 molecular and genomic surveillance may inform public health policies including vaccination strategies and enable a proactive approach to controlling coronavirus disease 2019 spread as the virus evolves.

The SARS-CoV-2 Variant Omicron Is Able to Escape Vaccine-Induced Humoral Immune Responses, but Is Counteracted by Booster Vaccination.

The SARS-CoV-2 variant Omicron has spread world-wide and is responsible for rapid increases in infections, including in populations with high vaccination rates. Here, we analysed in the sera of vaccinated individuals the antibody binding to the receptor-binding domain (RBD) of the spike protein and the neutralization of wild-type (WT), Delta (B.1.617.2), and Omicron (B.1.1.529; BA.1) pseudotyped vectors. Although sera from individuals immunized with vector vaccines (Vaxzevria; AZ and COVID-19 Janssen, Ad26.COV2.S; J&J) were able to bind and neutralize WT and Delta, they showed only background levels towards Omicron. In contrast, mRNA (Comirnaty; BNT) or heterologous (AZ/BNT) vaccines induced weak, but detectable responses against Omicron. While RBD-binding antibody levels decreased significantly six months after full vaccination, the SARS-CoV-2 RBD-directed avidity remained constant. However, this still coincided with a significant decrease in neutralization activity against all variants. A third booster vaccination with BNT significantly increased the humoral immune responses against all tested variants, including Omicron. In conclusion, only vaccination schedules that included at least one dose of mRNA vaccine and especially an mRNA booster vaccination induced sufficient antibody levels with neutralization capacity against multiple variants, including Omicron.

Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination.

Waning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the Omicron variant. A first booster vaccination increases Omicron-RBD-binding IgG and IgA and neutralizing capacity. In comparison, the Wuhan isolate titers of the Omicron variant binding antibodies are 8.5 lower. After a third vaccination, induction of Omicron-RBD- and Wuhan-RBD-binding antibodies follows the same kinetic. Five to six months after the third vaccination, there are still Omicron-RBD-binding antibodies detectable, but 35.9 percent of the analyzed sera fail to neutralize the Omicron variant, while all sera efficiently neutralize the Delta isolate. In the case of the Wuhan-RBD, a significantly larger number of stable antigen-antibody complexes is formed than in Omicron-RBD. A fourth vaccination with mRNA-1273 temporarily restores levels of Omicron-, Delta- and Wuhan-specific antibodies. Comparing different booster strategies revealed that the breadth of the immune response is not affected by the vaccination regimen. Taken together, these data indicate that booster vaccinations (third and fourth dose) increase the breadth of the immune response, but there is a qualitative difference of antibodies with respect to the stability of antigen-antibody complexes and persistence of antibody titers.

Comparative Investigation of Methods for Analysis of SARS-CoV-2-Spike-Specific Antisera.

In light of an increasing number of vaccinated and convalescent individuals, there is a major need for the development of robust methods for the quantification of neutralizing antibodies; although, a defined correlate of protection is still missing. Sera from hospitalized COVID-19 patients suffering or not suffering from acute respiratory distress syndrome (ARDS) were comparatively analyzed by plaque reduction neutralization test (PRNT) and pseudotype-based neutralization assays to quantify their neutralizing capacity. The two neutralization assays showed comparable data. In case of the non-ARDS sera, there was a distinct correlation between the data from the neutralization assays on the one hand, and enzyme-linked immune sorbent assay (ELISA), as well as biophysical analyses, on the other hand. As such, surface plasmon resonance (SPR)-based assays for quantification of binding antibodies or analysis of the stability of the antigen-antibody interaction and inhibition of syncytium formation, determined by cell fusion assays, were performed. In the case of ARDS sera, which are characterized by a significantly higher fraction of RBD-binding IgA antibodies, there is a clear correlation between the neutralization assays and the ELISA data. In contrast to this, a less clear correlation between the biophysical analyses on the one hand and ELISAs and neutralization assays on the other hand was observed, which might be explained by the heterogeneity of the antibodies. To conclude, for less complex immune sera-as in cases of non-ARDS sera-combinations of titer quantification by ELISA with inhibition of syncytium formation, SPR-based analysis of antibody binding, determination of the stability of the antigen-antibody complex, and competition of the RBD-ACE2 binding represent alternatives to the classic PRNT for analysis of the neutralizing potential of SARS-CoV-2-specific sera, without the requirement for a BSL3 facility.