Characterization of Spheno-occipital Synchondrosis Fusion From Preadolescents to Young Adults Using Age and Cervical Vertebrae Maturation Index.

The purpose of this study was to characterize the spheno-occipital synchondrosis fusion (SOSF) from preadolescents to young adults. A total of 630 Korean subjects (308 men, 322 women; age range, 6-18 y) were divided into 26 groups according to sex and age. After 3-dimensional computed tomography (CT) images were reoriented using the Frankfort horizontal (FH) plane, mid-sagittal plane, and frontal plane via ON3D software (3DONS), the cervical vertebrae maturation index (CVMI) and SOSF stages were identified using 6-stage and 5-stage scoring systems, respectively. The distributions of stage in each group were statistically investigated. Women showed early appearance and a short range of onset (CVMI stage 2, SOSF stage 2), middle (CVMI stage 4, SOSF stage 3 and stage 4), and completion (CVMI stage 6, SOSF stage 5), indicating rapid skeletal maturation compared with men. In both males and females, there were strong positive correlations between age and CVMI stage (rs=0.902, rs=0.890), between age and SOSF stage (rs=0.887, rs=0.885), and between CVMI and SOSF stages (rs=0.955, rs=0.964) (all P<0.001). The mean ages at SOSF stage 3 and stage 4 (12.7~13.9 y in males and 11.0~12.5 y in females) could be used as indicators of the pubertal growth peak. Regression equations for SOSF stage (y), age (a), and CVMI stage (b) were as follows: y=1.355-(0.133×a)+(0.29007×b)+(0.041×a×b) for males (r2=0.9496); y=1.305-(0.158×a)+(0.455×b)+(0.036×a×b) for females (r2=0.9606). Ordinal logistic regression analyses with the proportional odds model showed that females had more advanced SOSF stages than males (odds ratio: 1.972; 95% CI: 1.063-3.658, P<0.05). Our findings may provide basic references for CVMI and SOSF from preadolescents to young adults.

Association between Condylar Bone Density and Disk Displacement in the Temporomandibular Joint.

Measuring bone density (BD) is a common method of determining bone quality; however, the relationship between condylar BD and the occurrence of temporomandibular joint (TMJ) disorders has not been investigated. To address this knowledge gap, we aimed to investigate condylar BD in terms of TMJ disk displacement (TMJ DD) using computed tomography (CT) and magnetic resonance imaging (MRI). We classified TMJ MRI results according to the position of the disk: normal disk position (Normal), anterior disk displacement with reduction (ADDR), and anterior disk displacement without reduction (ADDNR). After retrospectively evaluating 86 female condyles, we determined the total, cortical, and trabecular BD in the upper-joint portion of the condyle and the whole condyle using CT data. To standardize condylar BD, we calculated the BD ratios by dividing the condylar BD by the cervical axis BD. The Kruskal-Wallis test analyzed the differences in BD measurements in the TMJ DD patient groups and showed significant between-group differences in condylar BD. The total and trabecular BD was significantly higher in ADDNR condyles than in Normal or ADDR condyles (Normal = ADDR < ADDNR). However, there was no significant difference in the cortical BD among the three TMJ DD groups. The BD ratios showed a similar tendency with condylar BD. These results suggest that increased condylar BD - specifically total and trabecular BD - may be significantly associated with ADDNR condyles. Our findings will help clinicians determine the course of treatment for patients with disk-related TMJ disorders.

Integration of cardiac proteome biology and medicine by a specialized knowledgebase.

RATIONALE: Omics sciences enable a systems-level perspective in characterizing cardiovascular biology. Integration of diverse proteomics data via a computational strategy will catalyze the assembly of contextualized knowledge, foster discoveries through multidisciplinary investigations, and minimize unnecessary redundancy in research efforts. OBJECTIVE: The goal of this project is to develop a consolidated cardiac proteome knowledgebase with novel bioinformatics pipeline and Web portals, thereby serving as a new resource to advance cardiovascular biology and medicine. METHODS AND RESULTS: We created Cardiac Organellar Protein Atlas Knowledgebase (COPaKB; www.HeartProteome.org), a centralized platform of high-quality cardiac proteomic data, bioinformatics tools, and relevant cardiovascular phenotypes. Currently, COPaKB features 8 organellar modules, comprising 4203 LC-MS/MS experiments from human, mouse, drosophila, and Caenorhabditis elegans, as well as expression images of 10,924 proteins in human myocardium. In addition, the Java-coded bioinformatics tools provided by COPaKB enable cardiovascular investigators in all disciplines to retrieve and analyze pertinent organellar protein properties of interest. CONCLUSIONS: COPaKB provides an innovative and interactive resource that connects research interests with the new biological discoveries in protein sciences. With an array of intuitive tools in this unified Web server, nonproteomics investigators can conveniently collaborate with proteomics specialists to dissect the molecular signatures of cardiovascular phenotypes.

HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.

Evolutional dynamics of highly pathogenic avian influenza H5N8 genotypes in wintering bird habitats: Insights from South Korea's 2020-2021 season.

The winter of 2020-2021 in South Korea witnessed severe outbreaks of Highly Pathogenic Avian Influenza (HPAI) viruses, specifically multiple genotypes of the H5N8 subtype. These outbreaks prompted an extensive investigation into the genetic characteristics and evolutionary dynamics of these viruses. Under the auspices of the National Institute of Wildlife Disease Control and Prevention (NIWDC), we conducted a nationwide surveillance program, collecting 7588 specimens from diverse wild bird habitats. Influenza A viruses were isolated at a rate of 5.0%, with HPAI H5N8 viruses accounting for 38.5% of isolates, predominantly found in wild bird carcasses (97.3%). Genetic analysis revealed the emergence of novel HPAI genotypes due to genetic reassortment events. G1 and G2 viruses were separately introduced into Korea, with G1 viruses displaying dynamic behavior, resulting in diverse sub-genotypes (G1-1 to G1-5) and mainly isolated from clinical specimens. Conversely, the G2 virus, introduced later, became the dominant strain consistently isolated mainly from bird carcasses (88.9%). These findings underscore the emergence of numerous novel HPAI genotypes shaped by multiple reassortment events in high-density wintering grounds of migratory birds. These sites act as hotspots for genetic exchanges, significantly influencing avian ecology, including resident bird species, and contributing to HPAI H5N8 evolution. The genetic diversity and ongoing evolution of these viruses highlight the need for vigilant surveillance and adaptive control measures. Recognizing the potential spillover to human populations, a One Health approach is essential to mitigate the evolving threats posed by avian influenza.

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.

Evidence of Greater Competitive Fitness of Erwinia amylovora over E. pyrifoliae in Korean Isolates.

Erwinia amylovora and E. pyrifoliae are the causative agents of destructive diseases in both apple and pear trees viz. fire blight and black shoot blight, respectively. Since the introduction of fire blight in Korea in 2015, the occurrence of both pathogens has been independently reported. The co-incidence of these diseases is highly probable given the co-existence of their pathogenic bacteria in the same trees or orchards in a city/ district. Hence, this study evaluated whether both diseases occurred in neighboring orchards and whether they occurred together in a single orchard. The competition and virulence of the two pathogens was compared using growth rates in vitro and in planta. Importantly, E amylovora showed significantly higher colony numbers than E. pyrifoliae when they were co-cultured in liquid media and co-inoculated into immature apple fruits and seedlings. In a comparison of the usage of major carbon sources, which are abundant in immature apple fruits and seedlings, E. amylovora also showed better growth rates than E. pyrifoliae. In virulence assays, including motility and a hypersensitive response (HR), E. amylovora demonstrated a larger diameter of travel from the inoculation site than E. pyrifoliae in both swarming and swimming motilities. E. amylovora elicited a HR in tobacco leaves when diluted from 1:1 to 1:16 but E. pyrifoliae does not elicit a HR when diluted at 1:16. Therefore, E. amylovora was concluded to have a greater competitive fitness than E. pyrifoliae.

Micropattern-based nerve guidance conduit with hundreds of microchannels and stem cell recruitment for nerve regeneration.

Guiding the regrowth of thousands of nerve fibers within a regeneration-friendly environment enhances the regeneration capacity in the case of peripheral nerve injury (PNI) and spinal cord injury (SCI). Although clinical treatments are available and several studies have been conducted, the development of nerve guidance conduits (NGCs) with desirable properties, including controllable size, hundreds of nerve bundle-sized microchannels, and host stem-cell recruitment, remains challenging. In this study, the micropattern-based fabrication method was combined with stem-cell recruitment factor (substance P, SP) immobilization onto the main material to produce a size-tunable NGC with hundreds of microchannels with stem-cell recruitment capability. The SP-immobilized multiple microchannels aligned the regrowth of nerve fibers and recruited the host stem cells, which enhanced the functional regeneration capacity. This method has wide applicability in the modification and augmentation of NGCs, such as bifurcated morphology or directional topographies on microchannels. Additional improvements in fabrication will advance the regeneration technology and improve the treatment of PNI/SCI.

SARS-CoV-2 variants show temperature-dependent enhanced polymerase activity in the upper respiratory tract and high transmissibility.

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33°C compared to 37°C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33°C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.

Three-dimensional analysis of the tooth movement and arch dimension changes in Class I malocclusions treated with first premolar extractions: a guideline for virtual treatment planning.

INTRODUCTION: Our objective was to analyze patterns of tooth movement and changes of arch dimension by superimposing 3-dimensional (3D) virtual models. METHODS: The sample consisted of 24 Korean adults with Class I malocclusion and minimal crowding, treated by first premolar extractions, sliding mechanics (0.022-in MBT brackets [3M Unitek, Monrovia, Calif] with 0.019 × 0.025-in stainless steel wire) and moderate anchorage. The 3D virtual maxillary casts at pretreatment and posttreatment were superimposed with the best-fit method. Linear and angular variables were measured with 3Txer program (Orapix, Seoul, Korea). Wilcoxon signed rank and Mann-Whitney tests were used for statistical analysis. RESULTS: There was no significant difference in the individual tooth movement between the right and left sides (P > 0.05). For the movement of each tooth, the maxillary central incisors (U1), lateral incisors (U2), and canines (U3) were significantly inclined lingually, extruded, and moved posteriorly and laterally. The maxillary second premolar (U5), first molar (U6), and second molar (U7) had significant mesial inward rotation, anterior movement, and contracted toward the midsagittal plane. The ratio of anteroposterior movement between the maxillary anterior and posterior teeth was 5:1. The amounts of contraction in U5, U6, and U7 were 1.4, 1.3, and 1.2 mm, respectively. When the amount of change between the adjacent teeth were compared, the linguoversion in U1 was significantly greater than that of U2. U3 and U5 showed significant opposite movements in all variables. There were differences only in angulation and vertical displacement between U6 and U7. CONCLUSIONS: Superimposition of 3D virtual models could be a guideline for precise virtual treatment planning.

Control of anterior segment using an antero-posterior lingual sliding retraction system: a preliminary cone-beam CT study.

BACKGROUND: This study was performed to evaluate the treatment effects of the antero-posterior lingual retractor (APLR), focusing on the 3-dimensional (3D) tooth movement of the maxillary anterior teeth and their alveolar bone levels. METHODS: En masse retraction was performed using either the C-lingual retractor (CLR, C-group, n = 9) or the antero-posterior lingual retractor (APLR, AP-group, n = 8). We evaluated 3D movement of the maxillary anterior teeth and alveolar bone levels, root length of the central incisors, long axes of the maxillary canines, and occlusal plane changes from CBCT images. RESULTS: After retraction, the central incisors were more significantly intruded and their root apex was more retracted in the AP-group. The long axis of the canine was well maintained in the AP-group. There were no differences in the steepness of occlusal plane and the incidence of alveolar bone loss or of root resorption during en masse retraction with the two retractors. CONCLUSIONS: The clockwise bowing effect of the anterior segment was less with the APLR, which prevented unwanted canine movement.

Relationships between temporomandibular joint disk displacements and condylar volume.

OBJECTIVES: The aim of this study was to assess the relationship between mandibular condylar volume and disk displacement status in adult males and females. STUDY DESIGN: We evaluated 122 temporomandibular joints in 61 patients using magnetic resonance imaging (MRI) and computed tomography (CT). MRI data were used to assign disk status as normal disk position (NR), disk displacement with reduction (DDR), or disk displacement without reduction (DDNR). CT data were used to calculate total condylar volume and its components, cortical volume, and trabecular volume. The relationships among condylar volume, disk status, and gender were tested with 2-way analysis of variance. RESULTS: Condylar volumes significantly correlated with disk displacement, tending to decrease as displacement increased. There were significant differences in both total condylar volume and trabecular volume among the DD status (NR > DDR > DDNR), whereas cortical volume was significantly different only between NR/DDR and DDNR (NR/DDR > DDNR). The volume decreases associated with temporomandibular joint DD were found in both males and females, with greater decreases in men than in women as DD progressed. CONCLUSIONS: Condylar volumes are significantly associated with disk displacement status. Joints with nonreducing disks showed the smallest condylar volumes in both males and females.

Quantitative three-dimensional analysis of root canal curvature in maxillary first molars using micro-computed tomography.

In endodontic therapy, access and instrumentation are strongly affected by root canal curvature. However, the few studies that have actually measured curvature are mostly from two-dimensional radiographs. The purpose of this study was to measure the three-dimensional (3D) canal curvature in maxillary first molars using micro-computed tomography (microCT) and mathematical modeling. Extracted maxillary first molars (46) were scanned by microCT (502 image slices/tooth, 1024 X 1024 pixels, voxel size of 19.5 x 19.5 x 39.0 microm) and their canals reconstructed by 3D modeling software. The intersection of major and minor axes in the canal space of each image slice were connected to create an imaginary central axis for each canal. The radius of curvature of the tangential circle was measured and inverted as a measure of curvature using custom-made mathematical modeling software. Root canal curvature was greatest in the apical third and least in the middle third for all canals. The greatest curvatures were in the mesiobuccal (MB) canal (0.76 +/- 0.48 mm(-1)) with abrupt curves, and the least curvatures were in the palatal (P) canal (0.38 +/- 0.34 mm(-1)) with a gradual curve. This study has measured the 3D curvature of root canals in maxillary first molars and reinforced the value of microCT with mathematical modeling.

Application of AMOR in craniofacial rabbit bone bioengineering.

Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.

A novel spectral library workflow to enhance protein identifications.

The innovations in mass spectrometry-based investigations in proteome biology enable systematic characterization of molecular details in pathophysiological phenotypes. However, the process of delineating large-scale raw proteomic datasets into a biological context requires high-throughput data acquisition and processing. A spectral library search engine makes use of previously annotated experimental spectra as references for subsequent spectral analyses. This workflow delivers many advantages, including elevated analytical efficiency and specificity as well as reduced demands in computational capacity. In this study, we created a spectral matching engine to address challenges commonly associated with a library search workflow. Particularly, an improved sliding dot product algorithm, that is robust to systematic drifts of mass measurement in spectra, is introduced. Furthermore, a noise management protocol distinguishes spectra correlation attributed from noise and peptide fragments. It enables elevated separation between target spectral matches and false matches, thereby suppressing the possibility of propagating inaccurate peptide annotations from library spectra to query spectra. Moreover, preservation of original spectra also accommodates user contributions to further enhance the quality of the library. Collectively, this search engine supports reproducible data analyses using curated references, thereby broadening the accessibility of proteomics resources to biomedical investigators. This article is part of a Special Issue entitled: From protein structures to clinical applications.

Gastric outlet obstruction due to gastric amyloidosis mimicking malignancy in a patient with ankylosing spondylitis.

Amyloidosis is a group of disorders characterized by the extracellular accumulation of insoluble, fibrillar proteins in various organs and tissues. It is classified, on the basis of the identity of the precursor protein, as primary, secondary, or familial amyloidosis. Gastrointestinal amyloidosis usually presents as bleeding, ulceration, malabsorption, protein loss, and diarrhea. However, gastric amyloidosis with gastric outlet obstruction mimicking linitis plastica is rare. We report a case of gastrointestinal amyloidosis with gastric outlet obstruction in a patient with ankylosing spondylitis. The patient was indicated for subtotal gastrectomy because of the aggravation of obstructive symptoms, but refused the operation and was transferred to another hospital. Three months later, the patient died of aspiration pneumonia during medical treatment.

Do sand blasted with large grit and acid etched surface treated mini-implants remain stationary under orthodontic forces?

OBJECTIVES: To determine the positional stability of sand blasted, large grit, and acid-etched (SLA) surface-treated mini-implants (C-implants) used as the exclusive source of anchorage during en masse retraction. MATERIALS AND METHODS: A retrospective clinical investigation was performed comparing pretreatment cone beam computed tomography (CBCT) images with those taken after en masse retraction of the six anterior teeth. Force was applied to 16 C-implants (1.8 mm in diameter, 8.5 mm in length) placed between the upper second premolars and first molars. Three-dimensional superimposition of CBCT data using mutual information was used to evaluate the positional difference of C-implants between preretraction and postretraction CBCT data. RESULTS: There was no significant difference in mini-implant position between the preretraction and postretraction CBCT evaluation. CONCLUSIONS: The SLA-coated C-implant provides stationary anchorage as well as stable anchorage during orthodontic tooth movement.