Background/Objectives: Despite hematoxylin and eosin (H&E) staining remaining the cornerstone of histopathological diagnosis, substantial intra- and inter-laboratory variability persists. This issue is increasingly relevant in Digital Pathology, where staining inconsistency may affect whole-slide image interpretation and the performance of image analysis algorithms. In the present work, we evaluated the diagnostic adequacy and non-inferiority of a novel tabs-based H&E histochemical staining method compared with conventional liquid reagents. Methods: Fifty formalin-fixed paraffin-embedded tissue samples from routine practice were sectioned in duplicate and stained either conventionally or using H&E Stain Tabs. After slide review, 14 representative tissue samples were selected, scanned at 40× magnification, and used to generate 24 matched image pairs at different magnifications. A blind online survey was completed by 13 expert pathologists using high-quality monitors. Participants assessed overall staining preference and rated stromal, epithelial, cytoplasmic, and nuclear staining quality. Non-inferiority was tested using a predefined margin of -0.10, and paired rating differences were analyzed using the Wilcoxon signed-rank test. Results: Across 312 paired evaluations, the tabs-based method was preferred in 120 cases (38.5%), conventional staining in 118 cases (37.8%), and no preference was expressed in 74 cases (23.7%). The tabs-based method met the criterion for non-inferiority compared with standard staining (z = 2.7). Rating-scale analysis showed significantly better stromal evaluation with the tablet-based method (z = 2.638; p = 0.008), whereas no significant differences were observed for epithelial, cytoplasmic, or nuclear staining. All evaluated images were considered diagnostically adequate. Conclusions: The tabs-based H&E stain was non-inferior to the conventional method and showed particularly favorable performance in the assessment of stromal components. These findings support its potential role in improving staining reproducibility and standardization, particularly in Digital Pathology workflows where pre-analytical and analytical consistency is critical.
Tubular adenoma of the breast (TAB) is a rare and understudied neoplasm, initially thought to represent a fibroadenoma (FA) variant. Recently, it has been shown that TABs lack MED12 mutations indicating a distinct pathogenesis, and an association between multiple TABs and Cowden syndrome (CS) has been described. We sought to evaluate PTEN status in TABs with immunohistochemistry (IHC) and identify other potential molecular alterations. Forty-nine TABs from 43 patients (3 with CS, 40 without known CS) were retrieved. All patients were female, and ages ranged from 15 to 54 years old (median: 25). All TABs were well circumscribed and composed of closely packed, bilayered tubules with minimal intervening stroma. CS patients had multiple, bilateral TABs. PTEN IHC showed loss of expression in the luminal cells in TABs from all CS patients while the expression was retained in sporadic/non-CS TABs. Whole exome and/or Sanger sequencing was performed on 34 sporadic TABs and identified somatic missense mutations at codon 95 of the beta-actin gene, ACTB, in 19 cases (56%). No pathogenic MED12 mutations were identified in 29 TABs with next-generation sequencing results. Overall, our findings highlight recurrent somatic ACTB mutations in more than half of sporadic TABs. CS-associated TABs but not sporadic TABs showed loss of PTEN expression. The presence of bilateral and/or multiple TABs should prompt PTEN IHC to rule out the possibility of CS.
In our previous work, we introduced the concept of torsion angular bin strings (TABS), which is a discrete vector representation of a conformer's torsional angles. Through this discretization, conformational states can be counted, yielding an estimate of the upper limit of the expected conformational ensemble size (nTABS). Besides nTABS being used as a quantitative measure of molecular flexibility, TABS itself is a way of grouping the conformers of a molecule without picking thresholds. This feature of TABS is especially valuable, as selecting suitable thresholds for metrics such as heavy-atom root-mean-square deviation (RMSD) or shape Tanimoto is highly system-dependent and can thus be challenging when working with large sets of molecules. Here, we describe the update to the nTABS algorithm of the TABS package since the last release. In addition, we present a classification study of conformer ensembles by TABS and compare it to classifications by a shape Tanimoto metric. Scientific contribution In contrast to our previous implementation, which handled molecular topological symmetry by enumerating all possible combinations that were simply permutations of one another, the new implementation treats TABS as mathematical objects governed by group theory, specifically Burnside's Lemma. This approach requires substantially less code and delivers a notable improvement in computational speed. The study also builds upon our previously developed framework for categorization comparisons between TABS and heavy-atom RMSD. Here, we show the results of a similar comparison with a shape Tanimoto metric, which further support the hypothesis that TABS encode the shape of conformers in a meaningful way.
The increasing frequency and intensity of forest fires demand innovative technologies to support firefighting and mitigate their impact on ecosystems and communities. This paper explores the application of untethered and tethered uncrewed aerial vehicles (UAVs) as aerial base station (ABS) in the context of forest fire management. We propose an ABS placement algorithm to serve UAV-user equipment (UE) in forest environments. The novelty of the proposed approach is to optimize the strategic ABS placement based on throughput requirements while serving multiple drone forest monitoring areas. We analyze and compare the performances of two aerial base stations (ABSs) such as an untethered ABS (UTABS) and a tethered ABS (TABS) for forest surveillance. We evaluate UTABS and TABS performances across single and multiple UAV-UE monitoring zones in forest environments under different network throughputs, wind effects, payload configurations, monitoring zone areas, communication frequencies, operating costs, etc. Our results indicate that while a UTABS offers superior flexibility, a TABS provides a cost-effective (78.2% reduction) and reliable solution to ensure long-term continuous forest fire surveillance operations.
This study investigated the role of interleukin-17 (IL-17) in giant cell arteritis (GCA), which has remained uncertain despite previous research suggesting a contribution of Th17 cells to the disease. Temporal artery biopsies (TABs) were cultured ex vivo in MATRIGEL with IL-17, secukinumab, or control IgG and subsequently analyzed using bulk RNA-sequencing and real-time quantitative polymerase chain reaction. Positive TABs with GCA features were compared to negative TABs or used to obtain in vitro cultures of myofibroblasts (MFs). Confocal microscopy analyzed IL-17 receptor expression. MFs and peripheral blood mononuclear cells cocultures were used to study T cell polarization. Transcriptomic analysis showed that secukinumab treatment of positive TABs reduced expression of genes linked to vascular inflammation, notably IL6. Real-time quantitative polymerase chain reaction analysis confirmed that secukinumab decreased messenger RNA encoding IL-6, CCL20, and granulocyte macrophage colony-stimulating factor (GM-CSF) in positive TABs, whereas IL-17 up-regulated them in negative TABs. No changes were observed regarding the expression of genes related to vascular remodeling. IL-17 receptor chains were expressed on MFs, and their expression was enhanced by interferon-γ (IFN-γ). Real-time quantitative polymerase chain reaction and Luminex analyses confirmed IL-17-driven upregulation of IL-6, CCL20, CCL2, GM-CSF, and vascular endothelial growth factor (VEGF) in MFs, which was reversed by secukinumab. Addition of IFN-γ to the culture increased the expression level of IL-17 receptor chains, resulting in a synergistic effect. Additionally, IL-17-pretreated MFs promoted Th17 polarization. IL-17 exacerbates vascular inflammation in GCA by activating MFs and synergizing with IFN-γ to increase production of proinflammatory cytokines (IL-6, GM-CSF), chemokines (CCL20, CCL2), and angiogenic factors (VEGF), indicating that IL-17 is a key contributor to disease pathogenesis.
To perform absolute quantification of miR-875-5p expression in temporal artery biopsies (TABs) of patients with giant cell arteritis (GCA), associate miR-875-5p copy number with histological and clinical characteristics of patients with GCA, and evaluate the diagnostic value of absolute copy number of miR-875-5p in GCA. The study included formalin-fixed, paraffin-embedded TABs of 45 treatment-naïve clinically proven patients with GCA, and 19 non-GCA controls. Of the included patients with GCA, 29 had histologically positive and 16 histologically negative TABs. Expression of miR-875-5p was assessed through utilization of quantitative real-time PCR (qPCR) and absolute quantification by digital PCR (dPCR). We determined significantly higher absolute copy number of miR-875-5p in histologically positive TABs of patients with GCA, compared to histologically negative TABs of GCA and non-GCA patients, which significantly correlated with the majority of TAB histopathological parameters and several clinical characteristics of patients with GCA. Notably, we showed a good diagnostic performance of absolute copy number of miR-875-5p in discriminating patients and controls, depending on the extent of vessel wall inflammation and remodeling in affected temporal arteries. Our study revealed that absolute quantification of miR-875-5p expression holds the potential to serve as a supporting biomarker in assessing vessel wall inflammation and remodeling in patients with GCA. Moreover, our results indicate the applicability of absolute quantification by dPCR in detecting low-abundance miRNAs in GCA-affected arterial tissue, whose limiting amounts hinder the utilization of classical qPCR.
To assess the bioequivalence of once-daily clonidine extended-release (XR) oral suspension (OS) to twice-daily clonidine XR tablets (TABs), which are approved for attention-deficit/hyperactivity disorder (ADHD). Study 1 (n = 20) evaluated an equivalent daily dose of clonidine XR OS versus TABs and clonidine XR OS under fed versus fasted conditions. Outcomes included the maximum plasma concentration (Cmax), the area under the analyte versus time curve (AUC) from 0 to the last analyte concentration (AUCt) and to infinity (AUCinf), and the half-life (Thalf). Study 2 (n = 19) evaluated AUC, Cmax, and the minimum concentration (Cmin) at steady state (SS). The ratios of geometric means and corresponding 90% CIs of pharmacokinetic parameters for each treatment were compared to the US Food and Drug Administration definition of bioequivalence (80%-125%). In Study 1 (mean [SD] age, 42 [11] years; 30% female; 10% Asian, 25% Black or African American, 5% Multiracial, 60% White; 40% Hispanic or Latino), the ratios (90% CIs) of clonidine XR OS to TABs were within the bioequivalence range accepted by the FDA for Cmax (95.6 [89.8, 101.8]), AUCt (97.2 [91.6, 103.1]) and AUCinf (96.1 [89.4, 103.4]); similar results were observed for clonidine XR OS under fed versus fasting conditions. The median (range) Thalf was 12.8 (8-24) hours. In study 2 (mean [SD] age, 43 [11] years; 42% female; 47% Asian, 26% Black or African American, 0% Multiracial, 26% White; 0% Hispanic or Latino), AUCt,ss and Cmax,ss were both within the acceptable range (97.7 [93.4, 102.1] and 107.9 [103.8, 112.2], respectively). The Cmin,ss for clonidine XR OS was ~26% lower than clonidine XR TABs (74.0 [69.3, 79.0]) but this difference was not considered clinically meaningful by the FDA. These results demonstrate that clonidine XR OS is bioequivalent to clonidine XR TABs and could fulfill a treatment gap as a liquid, once-daily, non-stimulant ADHD treatment option.
Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases in which macrophages play a central role in the pathogenesis. This study compared macrophage-related immune profiles in subacromial bursal tissues affected by PMR and temporal arteries affected by GCA to identify shared therapeutic targets. Subacromial bursa biopsies (SABBs) were obtained from patients with active PMR (n = 11). Temporal artery biopsies (TABs) were collected from 14 patients with GCA. Immunohistochemical staining was performed for macrophage markers [CD68, CD64, CD86, CD206 and folate receptor (FR) β] and macrophage-related cytokines (GM-CSF, IL-6, IL-23, IFN-γ, M-CSF and TNF-α). The percentage of positively stained cells was quantitatively scored. All macrophage-related markers and cytokines were expressed in both PMR-affected SABBs and GCA-affected TABs. The proportions of cells expressing macrophage markers (CD68, CD64, CD86 and CD206) and macrophage-related cytokines (GM-CSF, IL-6, IL-23, IFN-γ, M-CSF and TNF-α) were comparable between the two tissue types. However, the expression of FRβ was relatively higher in GCA TABs than in PMR SABBs. The macrophage immune profiles are remarkably similar in PMR SABBs and GCA TABs. This study underscores the concept of PMR and GCA as a disease spectrum and identifies shared therapeutic targets for both PMR and GCA.
A pivotal moment for the development of point of care diagnostics for COVID-19 was the validation of sample types that were alternatives to nasopharyngeal secretions. Specifically, anterior nasal fluid and saliva demonstrated a promising combination of high viral loads and minimal patient discomfort. However, only anterior nasal swabs were widely adopted, in part due to the complexity of saliva, its inherent variability between patients, and lack of a standardized method to collect a quality sample. Herein, we aim to standardize saliva sampling by repurposing FishburneTabspaper-based tabs originally designed to diagnose dry mouthas a sample collection tool for viral diagnostics. The workflow for operationalizing dried saliva is aligned with current sample processing methods for dried blood spot cards: (i) a patient collects a saliva sample with a FishburneTab, (ii) the FishburneTab is set on a flat surface to dry, and, after transport to a clinical laboratory, (iii) a standard hole punch is used to acquire punches for analysis. We show that FishburneTabs can reliably collect viral RNA, facilitate long-term dried sample storage, and achieve comparable performance to paired samples of liquid saliva (i.e., 92% accuracy). We validated this approach using a panel of 125 clinical samples, where dried saliva had a sensitivity of 85% and a specificity of 94% compared to paired liquid samples. These results suggest that FishburneTabs can be used to promote decentralized testing of upper respiratory viral infections through the self-collection of dried saliva.
Background: This study aimed to examine the association between the three subscales of the Transgender Attitudes and Beliefs Scale and professional commitment to treat transgender patients, and to test whether these associations were related to the physician's level of religiosity. Methods: A cross-sectional study of 109 family physicians was conducted using a self-administered questionnaire between October 2021 and July 2023 in the southern district of Clalit Healthcare Services. Confirmatory factor analysis and multi-group structural equation modeling were carried out. Main measures included TABS subscales, level of religiosity, and physicians' commitment to treat transgender patients. Results: Only the 'Human value' subscale was a statistically significant positive predictor of professional commitment to treat transgender patients among the whole population of physicians and among the subgroup of physicians with high religiosity at β = 0.36 (95% Confidence interval (CI) 0.11 to 0.61, p = 0.005), and β = 0.57 (95% CI 0.20 to 0.95, p = 0.003), respectively. Among physicians with a low level of religiosity there was a significant positive effect of the 'Interpersonal comfort' subscale on the professional commitment to treat transgender patients at β = 3.31 (95% CI 1.66 to 4.95, p < 0.001). Although the 'Sex/gender beliefs' subscale showed a significant negative association in the primary model (β = -2.91, 95% CI -4.64 to -1.17, p = 0.001), sensitivity analyses suggested that this finding should be interpreted with caution because of the strong correlation between TABS domains. Conclusions: Different TABS domains were associated with physicians' professional commitment to treat transgender patients across levels of religiosity. These findings can help tailor interventions more effectively to specific religiosity subgroups.
Background/Objectives: We aimed to report three novel MAGED2 variants associated with transient antenatal Bartter syndrome (TABS) and to summarize the prenatal and postnatal features of MAGED2-related TABS through case analysis and literature review. Methods: Three unrelated Chinese families with polyhydramnios-affected pregnancies underwent genetic testing. Clinical data, including prenatal imaging, delivery details, and postnatal outcomes were reviewed. A literature review of reported MAGED2 variants and associated phenotypes was conducted. Results: Three previously unreported MAGED2 variants were identified: two frameshift variants (c.1511del [p.Gly504Alafs*72] and c.338del [p.Pro113ArgfsTer4]) and one deletion (chrX:54,820,664-54,839,053 [GRCh37]). All fetuses presented with polyhydramnios; two were large for gestational age (LGA). Additional findings included ventriculomegaly and scrotal enlargement. Two male infants were delivered at 33 weeks following repeated amnioreduction, with transient postnatal electrolyte abnormalities and normal neurodevelopment at 3 and 4 years. One fetus with a frameshift variant died in utero at 26 + 1 weeks. A literature review of 53 cases revealed 38 distinct MAGED2 variants, predominantly null variants (65.8%). Polyhydramnios was the most consistent antenatal sign. No intellectual disability was reported in surviving individuals. Conclusions: These findings expand the MAGED2 mutational spectrum. Polyhydramnios and LGA represents the most frequent features in TABS. In fetuses presenting with early-onset severe polyhydramnios (around 19-20 weeks of gestation), particular attention should be paid to possible exon-level or partial deletions involving MAGED2 during genetic evaluation.
Maternal perinatal depression (MPD) is associated with reduced maternal plasma oxytocin (OXT) levels and an increased risk of autism spectrum disorder (ASD) in offspring. Using data from 23,218 Japanese mother-child pairs, we evaluated the relationship between MPD-assessed with the Kessler Psychological Distress Scale (K6) and the Edinburgh Postnatal Depression Scale (EPDS)-and autistic-related traits (ART) in toddlers, measured by the Tokyo Autistic Behavior Scale (TABS). We also tested the potential causal relationship of maternal stress exposure on OXT, its receptor (OXTR), and offspring outcomes using a prenatal stress-exposed mouse model. In the human cohort study, higher K6 or EPDS scores during pregnancy and postpartum were significantly associated with increased TABS scores in toddlers. Offspring of mothers with MPD (K6 or EPDS score ≥ 9) during pregnancy or postpartum exhibited a higher risk of ART (TABS score ≥ 15; P < 0.05). This risk was particularly pronounced in female toddlers exposed to MPD during pregnancy and postpartum (ORs: 5.805-9.367; P < 0.05). Female toddlers born to mothers with MPD also had lower birth weight, and their ART were positively correlated with K6 scores during mid-gestation and with impaired maternal bonding postpartum. In the mouse model, chronically stressed dams displayed depressive-like behaviors, and their female juveniles exhibited increased self-grooming and impaired social interaction. Furthermore, OXTR mRNA levels were significantly reduced in the prefrontal cortex of female juveniles from stressed dams. These findings suggest that MPD increases the risk of ART, particularly in females, highlighting potential sex-specific mechanisms underlying ASD susceptibility.
Transgender (TG) individuals experience persistent health disparities related to stigma, bias, and limited provider preparation. Few nursing programs use simulation that centers TG voices to address these gaps. To examine the relationship of TG standardized patient (TG-SP) simulation on prelicensure nursing students' attitudes and beliefs using the Transgender Attitudes and Beliefs Scale (TABS) and to explore student perceptions through qualitative debriefing. A concurrent triangulation mixed-methods design was used. Thirteen nursing students participated in a TG-SP simulation. Pre- and post-simulation TABS surveys assessed attitudinal changes across three subscales. Focused debriefings and field notes were thematically analyzed. Statistically significant improvements were observed on selected TABS items. Qualitative analysis revealed four themes: increased comfort and confidence, the impact of authentic representation, enhanced empathy through lived experience, and commitment to inclusive practice. Community advisory board involvement and TG-SP ensured authenticity and cultural congruence, strengthening student learning.
The Society for Cardiovascular Pathology (SCVP) recently released a consensus statement on diagnosing and reporting temporal artery biopsies (TAB). The document addresses diagnostic challenges such as adventitial inflammation, absence of giant cells, and non-arteritis changes. It recommends a three-tiered diagnostic scheme and emphasizes recognizing other types of vasculitis although giant cell arteritis (GCA) is the most common type. In this study, we retrospectively reviewed archival TABs to evaluate the utility of this new statement. We identified all TABs from our files from 1/2022-12/2023. Slides were blindly reviewed without knowing the original diagnoses. Cases were categorized as active arteritis, no arteritis, or healed arterial injury per the consensus document. Active arteritis cases were further classified as GCA or non-GCA, and the presence of giant cells was noted. Results were compared with the original diagnoses to assess the diagnostic and reporting utility of the SCVP schema. We included 105 TABs from 102 patients (66 female, 36 male; ages 45-93 years; mean age 71 ± 10 years). Using the consensus guidelines, 12 cases were diagnosed as active arteritis. Notably, 8 of 12 cases did not display giant cells in the media, and 1 case showed an exuberant number of eosinophils, suggesting that non-GCA arteritis should be considered. These 12 cases plus another 2 were originally diagnosed as GCA; the latter 2 cases were reclassified as no arteritis, with a comment noting adventitial-only inflammation. Two additional cases were classified as no arteritis, with original descriptive diagnosis of chronic inflammation in only adventitia. The remaining 89 cases were diagnosed as no arteritis, consistent with the original diagnosis. We did not find any case of healed arterial injury. The most common non-arteritis findings were neointimal hyperplasia and internal elastic lamina calcifications, consistent with age-related changes. The new SCVP TAB consensus schema can be easily implemented in routine clinical practice. It is also helpful in formulating diagnoses for challenging cases, such as those with adventitial-only inflammation or non-GCA arteritis. Additionally, it provides a unified and consistent reporting scheme.
Mapping construction material stocks is essential for understanding socioeconomic metabolism and informing the circular economy. However, spatial material stock studies often produce coarse results owing to challenges in material intensity development. This paper introduces BUD-MI (Bottom-Up Data: Material Intensity), a material intensity data collection template designed with three core objectives: streamlining the data collection process during building sampling, supporting cumulative research while ensuring project-specific relevance, and enhancing the utility of results for the construction industry. BUD-MI aims to assist researchers, students, and construction practitioners in developing material intensity data in line with these three objectives. The development process required identifying material intensity challenges, eliciting requirements, mapping relevant domain work and creating missing ones, and assembling them all into BUD-MI. The template consists of three data input tabs, two mini-tools for data input assistance, four result generation tabs, and additional tabs for background data and ancillary information. A case study in Sheffield, UK, illustrates BUD-MI's functionalities, enabling bespoke material intensity results to be disaggregated across building elements and components. BUD-MI supports future material intensity data collection efforts, ensuring data quality, granularity, comparability, transferability, and availability, thereby advancing socioeconomic metabolism and circular economy research and practice. The online version contains supplementary material available at 10.1007/s44498-026-00044-w.
To evaluate the influence of ceramic shade on color matching of CAD-CAM lithium disilicate (Li-disilicate) crowns relative to corresponding shade tabs, assessed based on Commission Internationale de l'Eclairage (CIE) values and nominal shade. A cross-sectional study was conducted to determine the shades of CAD-CAM Li-disilicate crowns (VITA Classical shades A3, B3, C3, and D3; n=5 per shade) using a spectrophotometer, an intraoral scanner, and visual assessment by nine observers with varying dental experience. Crowns were cemented onto shade-matched abutment. Color differences (ΔEab and ΔE00) were measured with the spectrophotometer and compared with perceptibility and acceptability threshold. Trueness (%) of each method was calculated using the corresponding shade tab as the reference. Independent samples t-test and one-way analysis of variance were used to compare the CIE values of the crown samples and their corresponding shade tabs. Shade C3 showed the highest mean ΔEab (3.42 ± 0.32), exceeding the 3.3 acceptability threshold. ΔE00 values exceeded acceptability threshold of 1.8 for A3 (1.91 ± 0.61), B3 (1.93 ± 0.38), and C3 (2.82 ± 0.42). The spectrophotometer achieved 100% for A3, while B3 and C3 showed 0% trueness across spectrophotometer and intraoral scanner. Shade determined by human showed the lowest intra- and inter-method reliability. Shades of CAD-CAM Li-disilicate crowns influenced the degree of color mismatch, assessed by both CIE values and nominal shade. The greatest ΔE values were observed in shade C3 crowns, and the spectrophotometer showed the lowest trueness for shades B3 and C3 crowns, indicating inconsistency between CIE values and nominal shade.
Color perception is a subjective process that can vary considerably among individuals. However, limited research has examined gingival shade selection according to observer gender. According to observer gender and gingival site, the objectives of this study were: (1) to compare subjective visual gingival shade selections; (2) to evaluate the accuracy of these visual selections by determining the degree of agreement between subjective and instrumental shade matching (subjective versus objective shade matches); and (3) to analyze the clinical performance of visual gingival shade selection. A gingival color assessment was conducted in 34 participants across five gingival sites. Objective color measurements were obtained using the SpectroShade Micro spectrophotometer, and subjective shade selections were made using 15 ceramic gingival shade tabs. Eight male and eight female final-year undergraduate dental students visually selected the shade tab that best matched each gingival site. A single trained operator recorded the CIELAB color coordinates of each gingival site using the spectrophotometer and identified the objectively determined shade tab for each participant and site (i.e., the shade tab yielding the smallest color difference). Agreement between subjective selections and the objectively optimal shade tabs was evaluated and compared between groups using the χ2 test. Visual gingival shade-matching performance was further assessed by calculating color difference (ΔE00), defined as the CIEDE2000 color difference between the observer-selected shade tab and the measured gingival CIELAB coordinates. Based on perceptibility (PT = 1.1) and acceptability (AT = 2.8) thresholds, visual matches were classified as excellent, acceptable, moderately unacceptable, clearly unacceptable, or extremely unacceptable. Statistically significant differences (p < 0.05) were observed between male and female observers in all gingival sites except the attached gingiva. Shade tables 10 and 11 were most frequently selected in all sites except the mucogingival junction, where tables 6 and 5 predominated. Agreement rates between subjective selections and objectively optimal shade tabs ranged from 4.4% (mucogingival junction) to 18.4% (mesial papilla). ΔE00 values ranged from 1.38 to 20.27 in the mesial papilla, 0.37 to 19.54 in the distal papilla, 0.49 to 16.54 in the free gingival margin, 0.37 to 17.58 in the attached gingiva, and 0.56 to 23.61 in the mucogingival junction. Mean ΔE00 values (4.74-6.60) exceeded the clinically acceptable threshold for gingival color in all sites and for both genders. The percentage of moderately, clearly, or extremely unacceptable visual selections ranged from 76.7% (mesial papilla) to 93.4% (mucogingival junction). Significant gender differences were observed only in the mesial papilla (p < 0.001), where male observers showed a higher percentage of acceptable matches than female observers (27.9% vs. 18.8%). Both male and female undergraduate observers experienced difficulty selecting the gingival shade tab that most accurately represented the gingival color determined instrumentally when relying solely on visual perception. Visual gingival shade selection performed by inexperienced undergraduate observers demonstrated limited accuracy under the conditions of this study, as chromatic mismatches frequently exceeded clinically acceptable thresholds. In this pilot study involving inexperienced undergraduate observers, subjective visual shade matching demonstrated limited accuracy across all gingival sites and in both genders. Objective color measurement devices may provide a valuable complement to visual assessment by facilitating clinically valid gingival color records and supporting esthetic outcomes in restorative and prosthetic treatments.
Bovine herpesvirus type 1 (BHV-1) is the primary pathogen responsible for infectious rhinotracheitis in cattle, leading to significant economic losses in the cattle industry. Long non-coding RNAs (lncRNAs) are multifunctional transcriptional regulators that play a role in the regulation of host-virus-specific interactions. MDBK cells were infected with BHV-1, and the function of lncRNA-MSTRG.16919.1 was evaluated using siRNA-mediated knockdown, as well as lentivirus-mediated stable overexpression of TAK1 and TAB2, respectively. Subsequent analyses were performed via qPCR, Western blotting, and viral titration assays, with the interaction between lncRNA-MSTRG.16919.1 and TAK1 further validated by RNA immunoprecipitation (RIP) assay. Our previous study found that lncRNA-MSTRG.16919.1 is highly expressed in BHV-1 infected MDBK cells. Functional assays showed that its silencing reduced viral DNA replication, downregulated transcription and protein expression of glycoproteins gB and gD, and decreased virion production, indicating that it promotes BHV-1 proliferation. Further investigation revealed that knockdown of this lncRNA reduced protein levels of TAB1, TAB2, TAB3, and TAK1. RNA immunoprecipitation (RIP) assay demonstrated that endogenous lncRNA-MSTRG.16919.1 physically interacts with the TAK1 protein, particularly during BHV-1 infection. To validate the involvement of the TAK1/TABs complex, we overexpressed TAK1 or TAB2 in cells with lncRNA knockdown. Overexpression restored viral DNA synthesis, gB and gD expression, and virus titers, counteracting the suppression caused by lncRNA silencing. Moreover, TAK1 or TAB2 overexpression elevated protein levels of TAB3, TAB1, TAK1, NF-κB, and JNK. These results demonstrate that lncRNA-MSTRG.16919.1 facilitates BHV-1 replication by modulating the TAK1-TABs complex and suggesting the potential involvement of the NF-κB pathway. These findings provide foundational insights for studying the function and regulatory mechanisms of lncRNA-MSTRG.16919.1 in organisms, and contribute to the understanding of the pathogenic mechanisms of BHV-1, aiding in the prevention and control of bovine respiratory diseases.
Temporal artery biopsy (TAB) for suspected giant cell arteritis (GCA) represents an infrequent but important inpatient consultation for acute care surgery (ACS) services. Given the morbidity associated with delayed treatment, corticosteroids are often initiated before biopsy, raising questions about the diagnostic utility and impact of TAB in contemporary practice. We performed a review of all inpatient TABs completed by an ACS service at a tertiary center between March 2015 and January 2024 to characterize case volume, pathology results, and influence of biopsy findings on corticosteroid management. Sixty-four patients underwent TAB, the majority of whom were elderly and female, with visual symptoms and headache being the most common presenting complaints. Nearly all patients were initiated on high-dose corticosteroids prior to biopsy, with a median of two days between ACS consultation and procedure. Pathologic findings confirmed GCA in 10% of cases, with additional biopsies demonstrating intimal fibroplasia or equivocal inflammatory changes. Despite widespread steroid initiation, biopsy results influenced discharge management, as patients with negative pathology were more likely to undergo corticosteroid tapering prior to or shortly after discharge. The median American College of Rheumatology 1990 classification score was three, with just over half of patients meeting criteria for GCA. No TABs were performed during 2020, but biopsy volume increased substantially in the post-COVID period. These findings suggest that ACS services play an important role in the diagnostic evaluation of suspected GCA. Although corticosteroid therapy is frequently initiated prior to biopsy, TAB continues to yield clinically meaningful information that informs subsequent management decisions.
Giant cell arteritis (GCA) is the most prevalent vasculitis in the elderly of Caucasian ancestry, with the risk of visual loss as the most serious complication if the glucocorticoid therapy does not succeed. While imaging and temporal artery biopsy (TAB) remain diagnostic gold standards, new laboratory tests are needed to assess disease activity and follow-up monitoring. We aimed to characterize distinct proteomic signatures for the classification of polymyalgia rheumatica (PMR) and GCA (independent of concurrent therapy) and to identify specific markers of disease activity and markers that differentiate the two diseases. The plasma of 15 PMR and 13 GCA patients was analysed via mass spectrometry with the UltiMate 3000 nano-HPLC system coupled to an Orbitrap Eclipse mass spectrometer. Immunofluorescence analyses in TABs were performed to confirm the elevated plasma expression of S100A12. We identified 50 protein signatures characteristic of active GCA patients, and 83 signatures altered only in active PMR samples. Strikingly, both groups shared only 13 proteins with altered protein expression levels. The newly identified proteins point to activation of biological pathways not yet linked to the diseases: mitochondrial membrane activity (ACACA, SLC25A31) and clotting cascade (VWF, TUBB) in active GCA; erythrocyte integrity (SLC4A1, SPTA1), muscle contraction (MYLK, MYL6B/12B), and glucocorticoid resistance (PTGES3) in active PMR. Importantly, S100A12 was increased not only in plasma (~ 1.6-fold), but also in PMR and GCA TABs. Active PMR and active GCA patients share an unexpectedly small plasma proteome signature related to immune activation (8.9%: 13 proteins). Instead, active PMR is characterized by distinct erythrocyte and muscle contraction proteome changes, whereas active GCA appears driven by mitochondrial and clotting cascade alterations. Prospective, longitudinal validation studies of the described proteomic signatures might support the clinical classification of both diseases.