Reliability of Artificial Intelligence-based Cone Beam Computed Tomography Integration with Digital Dental Images.

This study aimed to introduce cone-beam computed tomography (CBCT) digitization and integration of digital dental images (DDI) based on artificial intelligence (AI)-based registration (ABR) and to evaluate the reliability and reproducibility using this method compared with those of surface-based registration (SBR). This retrospective study consisted of CBCT images and DDI of 17 patients who had undergone computer-aided bimaxillary orthognathic surgery. The digitization of CBCT images and their integration with DDI were repeated using an AI-based program. CBCT images and DDI were integrated using a point-to-point registration. In contrast, with the SBR method, the three landmarks were identified manually on the CBCT and DDI, which were integrated with the iterative closest points method. After two repeated integrations of each method, the three-dimensional coordinate values of the first maxillary molars and central incisors and their differences were obtained. Intraclass coefficient (ICC) testing was performed to evaluate intra-observer reliability with each method's coordinates and compare their reliability between the ABR and SBR. The intra-observer reliability showed significant and almost perfect ICC in each method. There was no significance in the mean difference between the first and second registrations in each ABR and SBR and between both methods; however, their ranges were narrower with ABR than with the SBR method. This study shows that AI-based digitization and integration are reliable and reproducible.

Metformin Suppresses Both PD-L1 Expression in Cancer Cells and Cancer-Induced PD-1 Expression in Immune Cells to Promote Antitumor Immunity.

Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells. Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay. A mouse xenograft tumor model was used to evaluate the effect of metformin on tumor growth, followed by flow-cytometric analysis using tumor-derived single-cell suspensions. Results: Metformin decreased AKT-mediated ß-catenin S552 phosphorylation and subsequent ß-catenin transactivation in an adenosine monophosphate-activated protein kinase (AMPK) activation-dependent manner, resulting in reduced CD274 (encoding PD-L1) transcription in cancer cells. Tumor-derived soluble factors enhanced PD-1 protein stability in NK and T cells via dissociation of PD-1 from ubiquitin E3 ligases and reducing PD-1 polyubiquitylation. Metformin inhibited the tumor-derived soluble factor-reduced binding of PD-1 to E3 ligases and PD-1 polyubiquitylation, resulting in PD-1 protein downregulation in an AMPK activation-dependent manner. These inhibitory effects of metformin on both PD-L1 and PD-1 expression ameliorated cancer-reduced cytotoxic activity of immune cells in vitro and decreased tumor immune evasion and growth in vivo. Conclusions: Metformin blocks both PD-L1 and PD-1 within the tumor microenvironment. This study provided a mechanistic insight into the efficacy of metformin in improving immunotherapy in human cancer.

Challenge for Trade-Off Relationship between the Mechanical Property and Healing Efficiency of Self-Healable Polyimide.

Polyimide is actively applied in various industrial fields because of its strong mechanical properties, owing to the interactions between the polymer chains. Fully aromatic imide structures exhibit high glass-transition temperatures due to the strong interactions between their chains, which hinder chain mobility. Therefore, preparing a material that exhibits self-healing at a low temperature of ≤100 °C and good mechanical properties is challenging. Thus, we prepared imides with four-component semiaromatic structures by adjusting the contents of 4,4'-(hexafluoroisopropylidene)diphthalic anhydride and 4,4'-(4,4'-isopropylidenediphenoxy)bis(phthalic anhydride) to yield four-component self-healable colorless polyimides (f-SH-CPIs) with novel structures, flexibilities, good mechanical properties, and low healing temperatures. The flexibilities and distances between the polymer chains, as the basis of the trade-off relationship between the mechanical properties and healing efficiency, were controlled. These materials may be used as substrates in wearable devices and multilayer insulation that may protect from space dust, cosmic rays, and satellite fragments.

Social capital building interventions and self-reported post-disaster recovery in Ofunato, Japan.

Evidence shows that communal resources, cohesion, and social infrastructure can mitigate shocks and enhance resilience. However, we know less about how specific social capital building interventions facilitate recovery in post-disaster environments. Using a survey of over 1000 residents of Ofunato, Japan after the 2011 Tohoku earthquake and tsunami, this study demonstrates that the individuals who actively participated in a community center-created for and led by neighborhood elders-reported higher levels of family and neighborhood recovery than similar individuals who did not participate. Results from ordinal logistic regression analyses, propensity score matching (PSM) and coarsened exact matching (CEM) show arguably stronger causal links between bottom-up, microlocal programs to boost connections in post-disaster areas and post-disaster outcomes. Community-based programs that strengthen social ties even among elderly residents can measurably improve their recoveries.

Nanodiamond as a Cytokine Sponge in Infectious Diseases.

Cytokine release syndrome (CRS) is a systemic inflammatory response resulting in overexpression of cytokines in serum and tissues, which leads to multiple-organ failure. Due to rapid aggravation of symptoms, timely intervention is paramount; however, current therapies are limited in their capacity to address CRS. Here, we find that the intravenous injection of highly purified detonation-synthesized nanodiamonds (DND) can act as a therapeutic agent for treating CRS by adsorbing inflammatory cytokines. Highly purified DNDs successfully inactivated various key cytokines in plasma from CRS patients with pneumonia, septic shock, and coronavirus disease 2019 pandemic (COVID-19). The intravenous injection of the DND samples in a mouse sepsis model by cecal ligation and puncture significantly improved survival rates and prevented tissue damage by reducing the circulating inflammatory cytokines. The results of this study suggest that the clinical application of highly purified DND can provide survival benefits for CRS patients by adsorbing inflammatory cytokines.

Cerebrospinal Fluid-philic and Biocompatibility-Enhanced Soft Cranial Window for Long-Term In Vivo Brain Imaging.

Soft, transparent poly(dimethyl siloxane) (PDMS)-based cranial windows in animal models have created many opportunities to investigate brain functions with multiple in vivo imaging modalities. However, due to the hydrophobic nature of PDMS, the wettability by cerebrospinal fluid (CSF) is poor, which may cause air bubble trapping beneath the window during implantation surgery, and favorable heterogeneous bubble nucleation at the interface between hydrophobic PDMS and CSF. This may result in excessive growth of the entrapped bubble under the soft cranial window. Herein, to yield biocompatibility-enhanced, trapped bubble-minimized, and soft cranial windows, this report introduces a CSF-philic PDMS window coated with hydroxyl-enriched poly(vinyl alcohol) (PVA) for long-term in vivo imaging. The PVA-coated PDMS (PVA/PDMS) film exhibits a low contact angle θACA (33.7 ± 1.9°) with artificial CSF solution and maintains sustained CSF-philicity. The presence of the PVA layer achieves air bubble-free implantation of the soft cranial window, as well as induces the formation of a thin wetting film that shows anti-biofouling performance through abundant water molecules on the surface, leading to long-term optical clarity. In vivo studies on the mice cortex verify that the soft and CSF-philic features of the PVA/PDMS film provide minimal damage to neuronal tissues and attenuate immune response. These advantages of the PVA/PDMS window are strongly correlated with the enhancement of cortical hemodynamic changes and the local field potential recorded through the PVA/PDMS film, respectively. This collection of results demonstrates the potential for future microfluidic platforms for minimally invasive CSF extraction utilizing a CSF-philic fluidic passage.

Spatially multiplexed dielectric tensor tomography.

Dielectric tensor tomography (DTT) enables the reconstruction of three-dimensional (3D) dielectric tensors, which provides a physical measure of 3D optical anisotropy. Herein, we present a cost-effective and robust method of DTT using spatial multiplexing. Exploiting two orthogonally polarized reference beams with different angles in an off-axis interferometer, two polarization-sensitive interferograms were multiplexed and recorded using a single camera. Then, the two interferograms were demultiplexed in the Fourier domain. By measuring the polarization-sensitive fields for various illumination angles, 3D dielectric tensor tomograms were reconstructed. The proposed method was experimentally demonstrated by reconstructing the 3D dielectric tensors of various liquid-crystal (LC) particles with radial and bipolar orientational configurations.

Molecular and Morphological Characteristics of a New Species Collected from an Insect (Cicindela transbaicalica) in Korea.

To exploit insect-derived fungi, insects were collected from seven different regions in Korea, including Gyeongbuk, Goryeong, and several fungi were isolated from them. A fungal strain designated 21-64-D was isolated from riparian tiger beetle (Cicindela transbaicalica) and morphologically identified as a species belonging to the genus Oidiodendron. Phylogenetic analysis using the nucleotide sequences of internal transcribed spacer (ITS) regions and the partial sequence of the large subunit of the nuclear ribosomal RNA (LSU) gene revealed the distinct phylogenetic position of the isolate among recognized Oidiodendron species including its closest neighbors O. chlamydosporicum, O. citrinum, O. maius, and O. pilicola. The hyphal and conidial morphology of the strain, particularly club-shaped hyphae, clearly differentiated it from its close relatives. Results indicated that 21-64-D is a novel species in the genus Oidiodendron, for which the name Oidiodendron clavatum sp. nov. is proposed.

Highly Soluble Fluorinated Polyimides Synthesized with Hydrothermal Process towards Sustainable Green Technology.

Polyimides, a widely used engineering plastic, require use of large amounts of toxic and hazardous organic solvents which threaten our daily lives, calling for new and easy synthetic methods for sustainable environmentally friendly development. In this paper, highly soluble fluorinated polyimides based on 4,4'-(hexafluoroisopropylidene) diphthalic anhydride were synthesized via hydrothermal process without using any toxic organic solvents and the advantages of the newly demonstrated synthetic methods are shown by comparative analysis performed with the two conventional synthetic methods using organic solvent: thermal and chemical imidization. Lower temperature is required (~200 °C) compared to thermal imidization and functional groups for high fusibility formed more easily compared to chemical imidization. According to the comparative analysis, hydrothermally synthesized PIs showed excellent solubility and maintained high thermal stability (>500 °C) and glass transition temperature (>300 °C) compared to conventional PI. The hydrothermally synthesized polyimide is much more convenient to store and manage than other form of polyimide which is much more stable when it is exposed to humidity as it is a powder form. The hydrothermal synthetic method is verified to be a "Green" and facile method for sustainable PI synthesis.

Effect of Aluminum Flakes on Mechanical and Optical Properties of Foam Injection Molded Parts.

Injection research using aluminum flakes has been conducted to realize metallic textures on the surface of plastic products. Several studies have focused on the effect of the orientation and quality of the flakes when using conventional injection molding methods; however, limited studies have focused on the foam injection molding method. In this study, we examined the orientation of aluminum flakes through foam injection with an inert gas and observed the changes in texture using a spectrophotometer and a gloss meter. The mechanical properties were also studied because the rigidity of the product, which is affected by the weight reduction that occurs during foaming, is an important factor. The results demonstrate that under foam injection molding, reflectance and gloss increased by 6% and 7 GU, respectively, compared to those obtained using conventional injection molding; furthermore, impact strength and flexural modulus increased by 62% and 15%, respectively. The results of this research can be applied to incorporate esthetic improvements to products and to develop functional parts.

Mechanical Properties of Biocomposites Using Polypropylene and Sesame Oil Cake.

Sesame oil cakes (SOC) produced during sesame oil production can be classified as plant residues. This study aims to use SOC as a composite material for injection molding. A biocomposite containing polypropylene (PP) and SOC, namely PP/SOC, was developed and its mechanical properties were evaluated. PP/SOC is largely divided into Homo-PP/SOC (HPS) based on Homo-PP and Block-PP/SOC (BPS) based on block-PP. The specimens containing 0-50 wt% SOC were prepared through extrusion and injection molding. As a result of the evaluation, SOC acted as a reinforcement in the matrix, and HPS and BPS showed improved flexural modulus by 36.4% and 37.3% compared to the neat PP, respectively. Tensile strength, on the other hand, decreased by 58% and 55.1%, respectively. To analyze the cause of this, cross-section observation was conducted through scanning electron microscope (SEM), and phase separation and voids were confirmed to be the cause of this. Impact strength of PP/SOC tended to vary depending on the type of matrix. HPS increased by 30.9% compared to neat PP, and BPS decreased by 25%. This tendency difference appears to be the result of SOC inhibiting crystallization of PP, and it has been confirmed through x ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. Moreover, PP/SOC can be manufactured at a low cost and is environmentally friendly because it utilizes SOC, a plant residue. It can also be applied to commercial products, such as food packaging, owing to its good moldability and improved mechanical properties.

The social impact of natural hazards: a multi-level analysis of disasters and forms of trust in mainland China.

This study aimed to assess the multi-level effects of natural hazards on trust in Chinese society. Drawing on the Chinese General Social Survey conducted in 2012 and provincial disaster damage records, it examined the association between individuals' past experiences of disasters and province-level damage (measured by the number of affected people, deaths, and economic loss) and various forms of trust: in-group; out-group; generalised; and political. The findings indicate that Chinese individuals with experience of disasters have higher levels of out-group trust but lower levels of political trust. Similarly, at the province level, damage owing to disasters over the past three years (2009-11) positively impacted on residents' out-group trust while negatively affecting their political trust. However, when provincial damage was aggregated for disasters over the past five years (2007-11), which included the devastating Sichuan earthquake on 12 May 2008, only total deaths had a positive effect on generalised trust.

Neurovascular Coupling under Chronic Stress Is Modified by Altered GABAergic Interneuron Activity.

Neurovascular coupling (NVC), the interaction between neural activity and vascular response, ensures normal brain function by maintaining brain homeostasis. We previously reported altered cerebrovascular responses during functional hyperemia in chronically stressed animals. However, the underlying neuronal-level changes associated with those hemodynamic changes remained unclear. Here, using in vivo and ex vivo experiments, we investigate the neuronal origins of altered NVC dynamics under chronic stress conditions in adult male mice. Stimulus-evoked hemodynamic and neural responses, especially beta and gamma-band local field potential activity, were significantly lower in chronically stressed animals, and the NVC relationship, itself, had changed. Further, using acute brain slices, we discovered that the underlying cause of this change was dysfunction of neuronal nitric oxide synthase (nNOS)-mediated vascular responses. Using FISH to check the mRNA expression of several GABAergic subtypes, we confirmed that only nNOS mRNA was significantly decreased in chronically stressed mice. Ultimately, chronic stress impairs NVC by diminishing nNOS-mediated vasodilation responses to local neural activity. Overall, these findings provide useful information in understanding NVC dynamics in the healthy brain. More importantly, this study reveals that impaired nNOS-mediated NVC function may be a contributory factor in the progression of stress-related diseases.SIGNIFICANCE STATEMENT The correlation between neuronal activity and cerebral vascular dynamics is defined as neurovascular coupling (NVC), which plays an important role for meeting the metabolic demands of the brain. However, the impact of chronic stress, which is a contributory factor of many cerebrovascular diseases, on NVC is poorly understood. We therefore investigated the effects of chronic stress on impaired neurovascular response to sensory stimulation and their underlying mechanisms. Multimodal approaches, from in vivo hemodynamic imaging and electrophysiology to ex vivo vascular imaging with pharmacological treatment, patch-clamp recording, FISH, and immunohistochemistry revealed that chronic stress-induced dysfunction of nNOS-expressing interneurons contributes to NVC impairment. These findings will provide useful information to understand the role of nNOS interneurons in NVC in normal and pathological conditions.

Longitudinal study of hemodynamics and dendritic membrane potential changes in the mouse cortex following a soft cranial window installation.

The soft cranial window using polydimethylsiloxane allows direct multiple access to neural tissue during long-term monitoring. However, the chronic effects of soft window installation on the brain have not been fully studied. Here, we investigate the long-term effects of soft window installation on sensory-evoked cerebral hemodynamics and neuronal activity. We monitored the brain tissue immunocytohistology for 6 weeks postinstallation. Heightened reactive astrocytic and microglia levels were found at 2 weeks postinstallation. By 6 weeks postinstallation, mice had expression levels similar to those of normal animals. We recorded sensory-evoked hemodynamics of the barrel cortex and LFP during whisker stimulation at these time points. Animals at 6 weeks postinstallation showed stronger hemodynamic responses and focalized barrel mapping than 2-week postoperative mice. LFP recordings of 6-week postoperative mice also showed higher neural activity at the barrel column corresponding to the stimulated whisker. Furthermore, the expression level of interleukin- 1 ß was highly upregulated at 2 weeks postinstallation. When we treated animals postoperatively with minocycline plus N-acetylcystein, a drug-suppressing inflammatory cytokine, these animals did not show declined hemodynamic responses and neuronal activities. This result suggests that neuroinflammation following soft window installation may alter hemodynamic and neuronal responses upon sensory stimulation.

Intratumoral Spatial Heterogeneity at Perfusion MR Imaging Predicts Recurrence-free Survival in Locally Advanced Breast Cancer Treated with Neoadjuvant Chemotherapy.

Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features. A network strategy was used to integrate all image features and classify patients into different risk groups. The prognostic value of imaging-based stratification was evaluated in relation to clinical-pathologic factors with multivariable Cox regression. Results Three intratumoral subregions with high, intermediate, and low MR perfusion were identified and showed high consistency between the two cohorts. Patients in both cohorts were stratified according to network analysis of multiregional image features regarding RFS (log-rank test, P = .002 for both). Aggressive tumors were associated with a larger volume of the poorly perfused subregion as well as interaction between poorly and moderately perfused subregions and surrounding parenchyma. At multivariable analysis, the proposed MSI-based marker was independently associated with RFS (hazard ratio: 3.42; 95% confidence interval: 1.55, 7.57; P = .002) adjusting for age, estrogen receptor (ER) status, progesterone receptor status, human epidermal growth factor receptor type 2 (HER2) status, tumor volume, and pathologic complete response (pCR). Furthermore, imaging helped stratify patients for RFS within the ER-positive and HER2-positive subgroups (log-rank test, P = .007 and .004) and among patients without pCR after neoadjuvant chemotherapy (log-rank test, P = .003). Conclusion Breast cancer consists of multiple spatially distinct subregions. Imaging heterogeneity is an independent prognostic factor beyond traditional risk predictors.

A Quantitative CT Imaging Signature Predicts Survival and Complements Established Prognosticators in Stage I Non-Small Cell Lung Cancer.

PURPOSE: Prognostic biomarkers are needed to guide the management of early-stage non-small cell lung cancer (NSCLC). This work aims to develop an image-based prognostic signature and assess its complementary value to existing biomarkers. METHODS AND MATERIALS: We retrospectively analyzed data of stage I NSCLC in 8 cohorts. On the basis of an analysis of 39 computed tomography (CT) features characterizing tumor and its relation to neighboring pleura, we developed a prognostic signature in an institutional cohort (n = 117) and tested it in an external cohort (n = 88). A third cohort of 89 patients with CT and gene expression data was used to create a surrogate genomic signature of the imaging signature. We conducted further validation using data from 5 gene expression cohorts (n = 639) and built a composite signature by integrating with the cell-cycle progression (CCP) score and clinical variables. RESULTS: An imaging signature consisting of a pleural contact index and normalized inverse difference was significantly associated with overall survival in both imaging cohorts (P = .0005 and P = .0009). Functional enrichment analysis revealed that genes highly correlated with the imaging signature were related to immune response, such as lymphocyte activation and chemotaxis (false discovery rate < 0.05). A genomic surrogate of the imaging signature remained a significant predictor of survival when we adjusted for known prognostic factors (hazard ratio, 1.81; 95% confidence interval, 1.34-2.44; P < .0001) and stratified patients within subgroups as defined by stage, histology, or CCP score. A composite signature outperformed the genomic surrogate, CCP score, and clinical model alone (P < .01) regarding concordance index (0.70 vs 0.62-0.63). CONCLUSIONS: The proposed CT imaging signature reflects fundamental biological differences in tumors and predicts overall survival in patients with stage I NSCLC. When combined with established prognosticators, the imaging signature improves survival prediction.

Prognostic value and molecular correlates of a CT image-based quantitative pleural contact index in early stage NSCLC.

PURPOSE: To evaluate the prognostic value and molecular basis of a CT-derived pleural contact index (PCI) in early stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We retrospectively analysed seven NSCLC cohorts. A quantitative PCI was defined on CT as the length of tumour-pleura interface normalised by tumour diameter. We evaluated the prognostic value of PCI in a discovery cohort (n = 117) and tested in an external cohort (n = 88) of stage I NSCLC. Additionally, we identified the molecular correlates and built a gene expression-based surrogate of PCI using another cohort of 89 patients. To further evaluate the prognostic relevance, we used four datasets totalling 775 stage I patients with publically available gene expression data and linked survival information. RESULTS: At a cutoff of 0.8, PCI stratified patients for overall survival in both imaging cohorts (log-rank p = 0.0076, 0.0304). Extracellular matrix (ECM) remodelling was enriched among genes associated with PCI (p = 0.0003). The genomic surrogate of PCI remained an independent predictor of overall survival in the gene expression cohorts (hazard ratio: 1.46, p = 0.0007) adjusting for age, gender, and tumour stage. CONCLUSIONS: CT-derived pleural contact index is associated with ECM remodelling and may serve as a noninvasive prognostic marker in early stage NSCLC. KEY POINTS: • A quantitative pleural contact index (PCI) predicts survival in early stage NSCLC. • PCI is associated with extracellular matrix organisation and collagen catabolic process. • A multi-gene surrogate of PCI is an independent predictor of survival. • PCI can be used to noninvasively identify patients with poor prognosis.

Influence of Glyoxal on Preparation of Poly(Vinyl Alcohol)/Poly(Acrylic Acid) Blend Film.

The preparation of a poly(vinyl alcohol)/poly(acrylic acid)/glyoxal film (PVA = poly(vinyl alcohol); PAA = poly(acrylic acid)) with high tensile strength and hydrophobic properties by using the crosslinking reaction for OH group removal is reported herein. PAA was selected as a crosslinking agent because the functional carboxyl group in each monomer unit facilitates reaction with PVA. The OH groups on unreacted PVA were removed by the addition of glyoxal to the PVA/PAA solution. The chemical properties of the PVA/PAA films were investigated using Fourier transformation infrared spectroscopy and the thermal properties of the PVA/PAA/glyoxal films were investigated by means of differential scanning calorimetry and thermogravimetric analysis. A tensile strength of 48.6 N/mm2 was achieved at a PVA/PAA ratio of 85/15 for the PVA/PAA film. The tensile strength of the cross-linked PVA/PAA/glyoxal film (10 wt% glyoxal) was increased by 55% relative to the pure PVA/PAA (85/15) film. The degree of swelling (DS) and solubility (S) of the 10 wt% (PVA/PAA = 85/15, wt%) film added 10 wt% glyoxal were 1.54 and 0.6, respectively.