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Anatomic-contour zirconia prostheses are usually cemented with resin cement. However, information regarding the effects of the zirconia shade and thicknesses on the translucency of the prosthesis, the intensity of the transmitted light beneath the prosthesis, and the subsequent degree of conversion in the resin cement is sparse.The purpose of this in vitro study was to investigate the translucency parameter in 3 anatomic-contour zirconia specimens of 2 shades at 5 different thicknesses and to investigate the transmitted light intensity and degree of conversion of the resin cement beneath the ceramic specimens by using a traditional zirconia and a lithium disilicate glass ceramic as controls.Ceramic specimens from 1 anatomic-contour zirconia in a generic shade (CAP FZ) and 2 anatomic-contour zirconias in A2 shade (Zirlux and Luxisse) were used. Lithium disilicate in HT A2 shade (IPS e.max CAD) and traditional zirconia in a generic shade (CAP QZ) were used as controls. A total of 125 ceramic specimens (n=25) were fabricated to a final specimen dimension of 12×12 mm and in thicknesses of 1.0, 1.25, 1.5, 1.75, and 2.0 mm according to the manufacturers' recommendations. The CIELab color space for all specimens placed against a white and black ground was measured with a spectrophotometer (CM-2600D), and the translucency parameters were calculated for the materials at various thicknesses. A light-polymerizing unit (DEMI LED) was used to polymerize the resin cement (Variolink II) placed beneath the ceramic specimens. Transmitted light intensity from the polymerization unit beneath the ceramic specimens was measured by using a spectrophotometer (MARC Resin Calibrator), and the transmittance of each specimen was calculated. The coefficient of absorption of each material was calculated from the regression analysis between the natural log of transmittance and specimen thickness. The degree of conversion of resin cement was measured by using a Fourier transformation infrared (FTIR) spectrophotometer. The results were analyzed by using 2-way ANOVA (α=.05). The relationship between the transmittance and the translucency parameter was evaluated by plotting the transmittance against the translucency parameter value of each specimen.The translucency parameter decreased with increasing thickness in all 5 material groups. All anatomic-contour zirconia had lower translucency parameters than e-max CAD (P.001). The same results were found for the intensity of the transmitted light (P.001). Both A2 shade anatomic-contour zirconia (Zirlux and Luxisse) showed significantly lower light transmittance than a generic shade anatomic-contour zirconia (CAP FZ) (P.001). The coefficients of absorption were found to range from 0.63 to 1.72 mmThe translucency parameter and the transmitted light intensity of ceramic material were influenced by the type of ceramic and the shade and thickness of the ceramic. The combined effects of layer thickness and the intensity of the transmitted light in the A2 shade anatomic-contour zirconia (Zirlux and Luxisse) resulted in a lower degree of conversion in resin cement than in a generic shade anatomic-contour zirconia (CAP FZ) at layer thicknesses of 1.75 and 2 mm.

We investigated whether the one-time application of polymer-coated urea (PCU) before transplanting could simultaneously improve the grain yield and nitrogen use efficiency (NUE) of japonica-indica hybrid rice (JIHR) through a field experiment. The local high-yield JIHR cultivar Chunyou-927 was field grown during the rice-growing seasons in 2019 and 2020. The experiment consisted of three treatments: no nitrogen application (0N), application of conventional urea (CU), and the one-time application of PCU. Grain yield was 1.0–1.3 t/ha higher, and agronomic NUE (kg grain yield increase per kg N applied) was 5.2–5.9 kg/kg higher, respectively, under the PCU treatment compared with the CU treatment across the two study years. When compared with the CU treatment, the PCU treatment could (1) improve root morphological trait, (2) reduce redundant vegetative growth during the early growth period, (3) increase matter production during the mid and late growth period, and (4) increase plant activity during the grain-filling period. Overall, our findings indicate that one-time PCU application before transplanting of the JIHR cultivar holds great promise for increasing grain yield and NUE.

To investigate the translucency parameters of traditional, milled, and 3D-printed denture base materials at 3 different thicknesses and the color masking ability of each material against a metallic background between different thicknesses.A traditional heat-polymerizing polymethylmethacrylate (PMMA) (H-Lucitone) material was used as the control group. Two milled pre-polymerized resin blocks (M-Lucitone and IvoBase) and five 3D-printed denture base materials (P-Lucitone, Dentca LP, Dentca OP, Formlabs, and Kulzer) were used as experimental groups. A total of 240 samples, (n = 30, per material) were fabricated to a final specimen dimension of 12×12 mm and in thicknesses of 1.0, 2.0, and 3.0 mm (n = 10 per thickness/material) according to the manufacturers' recommendations. The color coordinates (L*, a*, b*) in CIELab color space for all specimens placed against a white, black, and metallic background were measured with a spectrophotometer. The translucency parameters (TPThe TPThe results from this study provide clinicians and dental technicians with information regarding the selection of denture base materials to achieve desired color masking outcomes, according to available prosthetic space. Thicker prostheses significantly improved the color masking abilities of denture acrylic resins against a metallic background. In a thickness of 1 and 2 mm, the heat-polymerizing acrylic resin had a lower translucency parameter and better color masking ability. When the prosthesis thickness reached 3 mm, the milled acrylic resin had a lower translucency parameter and better color masking ability. When compared to the heat-polymerizing resin and milled acrylic resin materials, except for one 3D-printing resin (P-Lucitone), the color masking abilities of the remaining 3D-printing resin materials were low, regardless of prosthesis thickness.

AIM To introduce a new classification system for pulmonary arteriovenous malformations (PAVMs) based on the BRanches, ANgles and Diameter of the feeding artery (BRAND), which is intended provide a better understanding of the vascular structure of PAVMs and facilitate the selection of therapeutic strategies for embolisation. MATERIALS AND METHODS Twenty-one patients with PAVMs from 2005 to 2020 were reviewed retrospectively. According to angiographic morphology, classified the PAVMs using the BRAND classification. RESULTS A total of 41 PAVMs were treated with transcatheter embolisation. Based on the BRAND classification, there were four branches (9.8%), four acute angles (9.8%), and 32 occlusion sites >4 mm in diameter (78%). A total of 30 PAVMs (73.2%) were treated with occluders and plugs while the rest were embolised with coils (26.8%). Immediate technical success was achieved in all patients. In feeding arteries with acute angles, balloon-assisted tracking and trans-septal puncture techniques were used to facilitate the advancement of delivery systems. All origins of branches were preserved. Mean SaO2 increased significantly from 79.5 ± 7.5% before embolisation to 92 ± 5.3% after embolisation (p CONCLUSIONS BRAND classification is well suited to address the challenging feeding arteries of PAVMs and allow precise placement of the delivery system, leading to minimal procedural risk and high success rates.

Background Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, is widely applicable to anesthesia, analgesia, and sedation. However, the function and mechanisms of ketamine in the long-term learning and memory function of neonatal mice are unclear. Objective The present study aims to investigate whether long-term learning and memory function will be affected by multiple ketamine exposures in the early development period. Methods The mRNA and protein levels were measured by RT-qPCR and western blot, respectively. The Morris Water Maze test was performed to assess spatial learning and memory. Results We identified that neonatal exposure to ketamine downsized the positive neurons for microtubule-associated protein doublecortin (DCX) and Ki67 in hippocampal dentate gyrus at the juvenile and late adolescence stages. Double-labeling tests demonstrated that the counts of Iba1+ cells and Ki67+ cells were pronouncedly diminished with exposure to ketamine. Further, qPCR assays to screen the key factors predisposing the populations and maturation of microglia exhibited remarkable decline of CX3CR1 mRNA levels in ketamine group versus the control group. The close relation of microglia to synaptic plasticity was depicted by the significantly downregulated synaptic plasticity-related proteins NR2B and PSD-95 subsequent to multiple exposures to ketamine. Finally, we found that both the protein and mRNA levels of BDNF were markedly decreased in ketamine group versus the control group. Conclusion We found that multiple exposures to ketamine in neonatal mice lead to spatial learning and memory dysfunction. The alterations of microglial development and function are the possible mechanisms of long-term learning and memory impairment.

Purpose: To compare the amount of bone expansion, bone density change, and implant primary stability with an osseodensification technique to a conventional drilling protocol. Materials and methods: Twenty-four bovine rib segments (20 × 25 × 4 mm) with a 1-mm outer layer of cortical bone were randomly divided into two groups: an osseodensification group and a conventional drilling group. Each bone sample received one 4.1 × 10-mm implant. The density of the peri-implant bone before and after osteotomy was measured. After implant placement, primary stability was assessed. A laser surface scanner was used before and after implant placement to compare the dimension of crestal bone width and volumetric expansion. Histomorphometric analysis was performed to compare the bone-to-implant contact percentage (BIC%) of the two groups. Results: The peripheral and apical bone mineral density around the implants was significantly increased, and a statistically significantly higher peripheral BIC% was found in the osseodensification group. A significant increase in volume and bone width after implant placement was found in both groups. However, there were no significant differences in volume and bone width change at all three locations and in implant stability between the osseodensification and conventional drilling protocols. Conclusion: Within the limitations of this study, the osseodensification protocol increased the bone mineral density and primary bone-to-implant contact. Also, this study suggests that implant placement by osseodensification or conventional drilling can increase ridge dimensions in narrow alveolar ridges.

To evaluate the effects of 5 manufacturing technologies and 2 finish line designs on the trueness and dimensional stability of 3D-printed definitive dies at finish line regions under different storage conditions and time.Preparation of light chamfer and round shoulder finish lines were adopted individually on two mandibular first molar typodont teeth and digitalized as standard tessellation language (STL) files. A total of 240 samples (192 AM definitive dies and 48 definitive conventional stone dies) in 20 groups (n = 12) were manufactured based on 2 finishing line designs (chamfer and shoulder), 5 manufacturing technologies (4 additively manufactured technologies and conventional stone die), and 2 storage conditions (light exposure and dark). The 4 additively manufactured (AM) technologies include a DLP 3D-printer, an economic LED 3D-printer, a CLIP 3D-printer, and an SLA 3D-printer. All the study samples were distributed into two storage conditions. Subsequently, samples were digitalized to STL files at 3 different time points (within 36 hours, 1-month, and 3-months). A surface matching software was used to superimpose the sample STL files onto the corresponding original STL files with the best-fit alignment function. The trueness of each printed and stone definitive dies and their dimensional stabilities were measured by the root mean square (RMS, in mm). A linear mixed-effects model was used to test the effects of the finish line design, manufacturing technology, storage condition, and storage time on RMS values (α = 0.05).While finish line designs had no significant effects [F(1, 220) = 0.85, p 0.358], the manufacturing technologies [F(3, 220) = 33.02, p 0.001], storage condition [F(1, 220) = 4.11, p = 0.044], and storage time F(2, 440) = 10.37, p 0.001] affected the trueness and dimensional stability of 3D-printed dies at finish line regions. No significant interactions were found among the 4 factors. For the manufacturing technologies, Type IV stone groups and LCD 3D-printer groups had significantly higher RMS values than the other 3 printers (p 0.001) with no significant differences between Type IV stone and LCD 3D-printer groups (p = 0.577). DLP 3D-printer groups had higher RMS values than both SLA 3D-printer groups and CLIP 3D-printer groups (p 0.001). There were no significant differences between SLA 3D-printer groups and CLIP 3D-printer groups, p = 0.671. For the effects of storage conditions, RMS values were significantly higher in the groups stored with the direct light exposure than the ones stored in the dark, p = 0.044. In terms of the effects of storage time, the RMS values were significantly higher after 1-month storage, p = 0.002; and 3-month storage, p 0.001, than the ones at the immediate postmanufacturing stage. However, the RMS values after 1-month and 3-month storage were not significantly different from each other (p = 0.169).Manufacturing technologies, storage conditions, and storage time significantly affected the trueness and dimensional stability of 3D-printed dies at finish line regions, while finish line designs had no significant effects. Among the AM technologies tested, all have produced either comparable or truer 3D-printed dies than the Type IV dental stone dies, and the CLIP and SLA 3D-printers produced the best outcomes. 3D-printed dies showed significant distortion after 1-month and 3-months storage, especially under light exposure storage conditions. These findings may negate the clinical need to preserve 3D-printed dies, and digital data should be preserved instead.

Core samples taken from the bottom sediments of the glacial Lake Kucherla (Gorny Altai, Russia) clearly show annual layers represented by glacial clays. In our study, age-depth modeling is based the varve chronology and Cs-137, Pb-210 and C-14 isotope data. Our model is a highly accurate and reliable demonstration of the annual sedimentation history within the past 1400 years. The time series of geochemical indicators of climate change were obtained by synchrotron radiation micro X-ray fluorescence (SR- μ XRF) core scanning. Instrumental meteorological observations from 1940 to 2016 were used to construct transfer functions for the average annual temperatures and atmospheric precipitation amounts. A geochemical trace of a catastrophic seismic event, the Mongolian earthquake of 1761, was found in the cross-section of the bottom sediments.

Lifestyle interventions are effective from the earliest years of childhood. To best promote health, lifestyle factors should be implemented for children and their families from birth. This includes introducing families to the benefits of a whole-food plant-based (WFPB) or plant-predominant diet, daily physical activity, positive family and peer social connections, avoidance of risky substances for caregivers, optimal sleep habits, and stress management and mindfulness for all family members. Through attention to these six pillars of lifestyle medicine, children and their families can succeed in initiating and maintaining optimal lifelong physical and mental health.

To investigate the effects of the manufacturing technologies on the surface (cameo and intaglio) accuracy (trueness and precision) of computer-aided design and computer-aided manufacturing (CAD-CAM) occlusal splints.The digital design of the master occlusal splint was designed in a CAD software program. Six groups (n = 10) were tested in this study, including Group 1 - Milling (Wax), Group 2 - Heat-polymerizing, Group 3 - Milling (M series), Group 4 - Milling (DWX-51/52D), Group 5 - 3D-printing (Cares P30), and Group 6 - 3D-printing (M2). The study samples were placed in a scanning jig fabricated from putty silicone and Type III dental stone. The study samples were then scanned with a laboratory scanner at the intaglio and cameo surfaces, and the scanned files were exported in standard tessellation language (STL) file format. The master occlusal splint STL file, was used as a reference to compare with all scanned samples at the intaglio and cameo surfaces in a surface matching software program. Root mean square (RMS, measured in mm, absolute value) values were calculated by the software for accuracy comparisons. Group means were used as the representation of trueness, and the standard deviation for each group was calculated as a measure of precision. Color maps were recorded to visualize the areas of deviation between study samples and the master occlusal splint file. The data were normalized and transformed to rank scores, and one-way ANOVA was used to test for the differences between the groups. Pairwise comparisons were made between different groups. Fishers least square differences were used to account for the family-wise error rate. A 5% significance level was used for all the tests.The null hypotheses were rejected. The manufacturing technologies significantly affected the trueness of occlusal splints at both intaglio and cameo surfaces (p 0.001). At the cameo surfaces, Group 1 - Milling (Wax) (0.03 ± 0.02 mm), Group 3 - Milling (M series) (0.04 ± 0.01 mm), and Group 4 - Milling (DWX-51/52D) (0.04 ± 0.01 mm) had the smallest mean RMS values and highest trueness. Group 3 had the smallest standard deviation and highest precision among all groups (p 0.001, except p = 0.005 when compared with Group 2). Group 5 had the largest standard deviation and lowest precision among all groups (p 0.001). At the intaglio surfaces, Group 1 - Milling (Wax) (0.06 ± 0.01 mm) had the smallest RMS values and highest trueness among all groups (p 0.001), and Group 2 - Heat-polymerizing (0.20 ± 0.03 mm) and Group 5 - 3D-printing (Cares P30) (0.15 ± 0.05 mm) had significantly larger mean RMS and standard deviation values than all other groups (p 0.001), with lowest trueness and precision. In the color maps, Group 2 - Heat-polymerizing and Group 5 - 3D-printing (Cares P30) showed the most discrepancies with yellow and red (positive discrepancies) in most areas, and Group 1 - Milling (Wax) showed the best and most uniform surface matching with the most area in green.The manufacturing technologies significantly affected the trueness and precision of occlusal splints at both intaglio and cameo surfaces. The 5-axis milling units and industrial-level CLIP 3D-printer could be considered to achieve surface accuracy of occlusal splints.

Significance The size of scientific fields may impede the rise of new ideas. Examining 1.8 billion citations among 90 million papers across 241 subjects, we find a deluge of papers does not lead to turnover of central ideas in a field, but rather to ossification of canon. Scholars in fields where many papers are published annually face difficulty getting published, read, and cited unless their work references already widely cited articles. New papers containing potentially important contributions cannot garner field-wide attention through gradual processes of diffusion. These findings suggest fundamental progress may be stymied if quantitative growth of scientific endeavors—in number of scientists, institutes, and papers—is not balanced by structures fostering disruptive scholarship and focusing attention on novel ideas., In many academic fields, the number of papers published each year has increased significantly over time. Policy measures aim to increase the quantity of scientists, research funding, and scientific output, which is measured by the number of papers produced. These quantitative metrics determine the career trajectories of scholars and evaluations of academic departments, institutions, and nations. Whether and how these increases in the numbers of scientists and papers translate into advances in knowledge is unclear, however. Here, we first lay out a theoretical argument for why too many papers published each year in a field can lead to stagnation rather than advance. The deluge of new papers may deprive reviewers and readers the cognitive slack required to fully recognize and understand novel ideas. Competition among many new ideas may prevent the gradual accumulation of focused attention on a promising new idea. Then, we show data supporting the predictions of this theory. When the number of papers published per year in a scientific field grows large, citations flow disproportionately to already well-cited papers; the list of most-cited papers ossifies; new papers are unlikely to ever become highly cited, and when they do, it is not through a gradual, cumulative process of attention gathering; and newly published papers become unlikely to disrupt existing work. These findings suggest that the progress of large scientific fields may be slowed, trapped in existing canon. Policy measures shifting how scientific work is produced, disseminated, consumed, and rewarded may be called for to push fields into new, more fertile areas of study.

Background Little is known about the extent to which an active cancer diagnosis increases bleeding and thromboembolic risks in atrial fibrillation (AF) patients. Data on major bleeding rates per antithrombotic management strategy are lacking in AF patients with active cancer. Purpose To examine the incidence rates of major bleeding per antithrombotic treatment in AF patients with active cancer and to examine whether cancer type impacts major bleeding and thromboembolic risks. Methods We used Danish population-based health care databases to conduct this cohort study. We included all incident AF (including atrial flutter) patients aged ≥50 years between January 1st 1995 and December 31st 2016, out of whom we identified AF patients who subsequently developed cancer. We used International Classification of Diseases 10th Revision codes to identify data on cancer type and outcomes (i.e. major bleeding, arterial and venous thromboembolism). We used Anatomical Therapeutic Chemical codes to provide information on antithrombotic treatment (e.g. no anticoagulant treatment, platelet inhibitors, vitamin K antagonists, direct oral anticoagulants, or a combination of antithrombotic drugs) which was evaluated as a time-dependent variable. The follow-up started from the incident cancer diagnosis until the occurrence of an outcome, death or the end of the two year follow-up. Incidence rates per 100 patient-years and adjusted hazard ratios were computed. Results 22,996 AF patients with a subsequent incident cancer diagnosis were included in the study. These patients had higher major bleeding and thromboembolic risk compared to those without cancer, with adjusted HRs of 2.11 (1.99–2.23) and 1.36 (1.27–1.44), respectively (Figure 1). Highest bleeding risk was observed for intracranial and respiratory cancer, while haematological and respiratory cancer were associated with highest thromboembolic risk. Bleeding risk increased with increasing number of antithrombotic drugs and was higher in AF patients with active cancer compared to those without, across all exposure categories (Figure 2). Conclusions Patients with AF and active cancer are at increased risk of major bleeding and thromboembolisms than those without cancer. Treatment with dual or triple antithrombotic therapy in AF patients with active cancer showed very high bleeding rates. Funding Acknowledgement Type of funding sources: None.

The impact of lipotoxicity on the development of lung fibrosis is unclear. Saturated fatty acids, such as palmitic acid (PA), activate endoplasmic reticulum (ER) stress, a cellular stress response associated with the development of idiopathic pulmonary fibrosis (IPF). We tested the hypothesis that PA increases susceptibility to lung epithelial cell death and experimental fibrosis by modulating ER stress. Total liquid chromatography and mass spectrometry were used to measure fatty acid content in IPF lungs. Wild-type mice were fed a high-fat diet (HFD) rich in PA or a standard diet and subjected to bleomycin-induced lung injury. Lung fibrosis was determined by hydroxyproline content. Mouse lung epithelial cells were treated with PA. ER stress and cell death were assessed by Western blotting, TUNEL staining, and cell viability assays. IPF lungs had a higher level of PA compared with controls. Bleomycin-exposed mice fed an HFD had significantly increased pulmonary fibrosis associated with increased cell death and ER stress compared with those fed a standard diet. PA increased apoptosis and activation of the unfolded protein response in lung epithelial cells. This was attenuated by genetic deletion and chemical inhibition of CD36, a fatty acid transporter. In conclusion, consumption of an HFD rich in saturated fat increases susceptibility to lung fibrosis and ER stress, and PA mediates lung epithelial cell death and ER stress via CD36. These findings demonstrate that lipotoxicity may have a significant impact on the development of lung injury and fibrosis by enhancing pro-death ER stress pathways.

Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix gene expression. Treatment of RA-ILD fibroblasts with the proteoglycan syndecan-2 (SDC2) yielded similar antifibrotic effects through regulation of PAD2 expression, phosphoinositide 3-kinase/Akt signaling, and Sp1 activation in a CD148-dependent manner. Furthermore, SDC2-transgenic mice exposed to bleomycin-induced lung injury in an inflammatory arthritis model expressed lower levels of PAD2 and were protected from the development of pulmonary fibrosis. Together, our results support a SDC2-sensitive profibrotic role for PAD2 in RA-ILD fibroblasts and identify PAD2 as a promising therapeutic target of RA-ILD.

PURPOSE To compare the intaglio surface trueness of obturator prosthesis bases manufactured by traditional compression molding, injection molding, and 3D printing techniques. MATERIALS AND METHODS A complete edentulous master cast with Aramany Class I maxillary defect was selected for this in vitro study. Four study groups (n = 10/group) were included in this study, Group A: Compression Molding, Group B: Injection Molding, and Group C: Cara Print 3D DLP Printer, and Group D: Carbon 3D DLS Printer. All obturator prostheses' intaglio surfaces were scanned with a laboratory scanner (E4; 3Shape Inc, New Providence, NJ) and the dimensional differences between study samples and their corresponding casts were calculated as the root mean square (measured in mm, absolute value) using a surface matching software (Geomagic design X; 3D Systems, Rock Hill, SC). One-way Analysis of variance (ANOVA) and Fisher's least significant difference (LSD) test were used to compare groups differences in RMS (α = 0.05). RESULTS There was a significant effect of manufacturing technique on the RMS values for the 4 conditions [F(3,36) = 5.743, p = 0.003]. Injection Molding (0.070 mm) and Compression Molding groups (0.076 mm) had a lower interquartile range, and the Cara Print 3D-Printer group (0.427 mm) and Carbon 3D-Printer (0.149 mm) groups had a higher interquartile range. The Injection Molding group showed the best and uniform surface matching with the most area in green in the color maps. The Injection Molding group (0.139 ± 0.049 mm) had significantly lower RMS than all other groups (p < 0.001 for all comparisons). Compression Molding (0.269 ± 0.057 mm), Cara Print 3D-Printer (0.409 ± 0.270 mm), and Carbon 3D-Printer (0.291 ± 0.082 mm) groups were not significantly different from each other (Compression Molding versus Carbon 3D-Printer, p = 0.59; Compression Molding versus Cara Print 3D-Printer, p = 0.25; Cara Print 3D-Printer versus Carbon 3D-Printer, p = 0.40). CONCLUSION Obturator prosthesis bases manufactured with injection molding technique showed better intaglio surface trueness than ones made by the compression molding technique and 3D printers. Although obturator prosthesis bases manufactured from different 3D printers showed similar trueness, a DLP 3D printer produced less consistent outcome than a DLS 3D printer.

Introduction Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. The purpose of this study was to investigate the efficacy of Bone Morphogenetic Protein-2 (BMP-2) to heal a critical sized defect (CSD) in two novel porcine SBD models. Materials and Methods Two CSDs were performed in Yucatan Minipigs including a 25.0-mm SBD treated with intramedullary nailing (IMN) and a 40.0-mm SBD treated with dual plating (ORIF). In control animals, the defect was filled with a custom spacer and a bovine collagen sponge impregnated with saline (IMN25 Cont, n = 8; ORIF40 Cont, n = 4). In experimental animals, the SBD was filled with a custom spacer and a bovine collage sponge impregnated with human recombinant BMP-2 (IMN25 BMP, n = 8; ORIF40 BMP, n = 4). Healing was quantified using monthly modified Radiographic Union Score for Tibia Fractures (mRUST) scores, postmortem CT scanning, and torsion testing. Results BMP-2 restored bone healing in all eight IMN25 BMP specimens and three of four ORIF40 BMP specimens. None of the IMN25 Cont or ORIF40 Cont specimens healed. mRUST scores at the time of sacrifice increased from 9.2 (±2.4) in IMN25 Cont to 15.1 (±1.0) in IMN25 BMP specimens (P Conclusions We have developed two porcine CSD models, including fixation with IMN and with dual-plate fixation. Porcine models are particularly relevant for SBD research as the porcine immunologic response to injury closely mimics the human response. BMP-2 restored healing in both CSD models, and the effects were evident within the first month after injury. These findings support the use of both porcine CSD models to investigate new therapies to heal SBDs.

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized. Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF). Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from syndecan-2 was evaluated for its therapeutic potential. Measurements and Main Results: CD148 expression was downregulated in IPF lungs and fibroblasts. In human IPF lung fibroblasts, silencing of CD148 increased extracellular matrix production and resistance to apoptosis, whereas overexpression of CD148 reversed the profibrotic phenotype. CD148 fibroblast-specific knockout mice displayed increased pulmonary fibrosis after bleomycin challenge compared with control mice. CD148-deficient fibroblasts exhibited hyperactivated PI3K/Akt/mTOR signaling, reduced autophagy, and increased p62 accumulation, which induced NF-κB activation and profibrotic gene expression. SDC2-pep reduced pulmonary fibrosis in vivo and inhibited IPF-derived fibroblast activation. In precision-cut lung slices from patients with IPF and control patients, SDC2-pep attenuated profibrotic gene expression in IPF and normal lungs stimulated with profibrotic stimuli. Conclusions: Lung fibroblast CD148 activation reduces p62 accumulation, which exerts antifibrotic effects by inhibiting NF-κB–mediated profibrotic gene expression. Targeting the CD148 phosphatase with activating ligands such as SDC2-pep may represent a potential therapeutic strategy in IPF.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. To identify cell-specific mechanisms underlying COPD pathobiology, we analysed single-cell RNA sequencing (scRNAseq) profiles of explanted lung tissue from subjects with advanced COPD or control lungs. Findings were validated with scRNAseq of lungs from mice exposed to 10 months of cigarette smoke (CS), isolated human alveolar epithelial cells, and immunostaining of human lung tissue samples. We identified a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance, exemplified by decreased expression of the stress-response gene NUPR1. Network analyses identified an important role for inflamed capillary endothelial cells in COPD, particularly through CXCL-motif chemokine signalling. Finally, we detected a metallothionein expressing macrophage subpopulation unique to COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD.

Purpose To use statistical process control for intensity-modulated radiation therapy (IMRT) quality assurance (QA) and improve tolerance limits and action limits. Methods An electronic portal imaging device (EPID) was selected to verify IMRT QA. The I-chart and the exponentially weighted moving averages (EWMA) chart were used to analyze the corresponding results. Results Twenty samples were used to enable the sampling requirements for building the control limits to be met. The I-chart showed that isolated data points beyond the control limits were mainly derived from complex plans. The EWMA made predictions of systematic errors earlier than the I-chart. Systematic errors primarily originated from the dose calibration on the EPID, and recalibrating the EPID could eliminate such errors. Conclusion Statistical process control is an effective tool to detect controllable and can be used in IMRT QA. After calibrating the EPID, the tolerance and action limits all improved and satisfied the requirements/recommended values of the AAPM TG-218 report.

Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce the portal venous pressure and relieve the clinical complications related to portal hypertension. However, hepatic encephalopathy (HE) is still the main complication post TIPS. Studies have shown that patients over 65 years old with liver function reserve in Child-Pugh grade C are the high-HE-risk group post TIPS, and early TIPS treatment can benefit the survival of these high-risk patients. In this study, TIPS was used to treat 60 cases aged65 years old and liver function reserve in Child-Pugh grade C (decompensated liver cirrhosis) with esophagogastric variceal bleeding. The clinical results of 1-year was observed and the porto systemic gradient (PSG) was evaluated. The relationship between the incidence of HE and the PSG of patients with and without HE were compared to evaluate the effect of PSG on the incidence of HE.经颈静脉肝内门-体分流术（TIPS）能有效地降低门静脉压力以及缓解门静脉高压相关的临床并发症。但是肝性脑病（HE）仍是TIPS术后主要并发症。有研究表明年龄65岁、肝功能Child-Pugh C级患者是发生TIPS术后HE的高危人群，且早期TIPS治疗能使这部分高危患者生存获益。对60例年龄65岁和肝功能Child-Pugh C级失代偿期肝硬化合并食管胃底静脉曲张破裂出血患者行TIPS治疗，观察1年的临床结果，评价门静脉压力梯度（PSG）与HE发生率的关系，再将无HE患者的PSG与有HE患者的PSG进行对比分析，评价PSG对HE发生率的影响。.

In this study, we leveraged a combination of single cell RNAseq, cytometry by time of flight (CyTOF), and flow cytometry to study the biology of a unique macrophage population in pulmonary fibrosis. Using the profiling data from 312,928 cells derived from 32 idiopathic pulmonary fibrosis (IPF), 29 healthy control and 18 chronic obstructive pulmonary disease (COPD) lungs, we identified an expanded population of macrophages in IPF that have a unique transcriptional profile associated with pro-fibrotic signature. These macrophages attain a hybrid transitional state between alveolar and interstitial macrophages, are enriched with biological processes of pro-fibrotic immune cells, and express novel surface markers and genes that have not been previously reported. We then applied single cell CyTOF to simultaneously measure 37 markers to precisely phenotype the uniquely expanded macrophage subset in IPF lungs. The SPADE algorithm independently identified an expanded macrophage cluster, and validated CD84 and CD36 as novel surface markers that highly label this cluster. Using a separate validation cohort, we confirmed an increase in CD84++CD36++ macrophage population in IPF compared to control and COPD lungs by flow cytometry. Further, using the signature from the IPF-specific macrophages and the LINCS drug database, we predicted small molecules that could reverse the signature of IPF-specific macrophages, and validated two molecules, CRT and Cucur, using THP-1 derived human macrophages and precision-cut lung slices (PCLS) from IPF patients. Utilizing a multi-dimensional translational approach, our work identified a novel and targetable population of macrophages found in end-stage pulmonary fibrosis.One Sentence SummarySingle cell RNAseq, CyTOF, and flow cytometry reveal the presence of an aberrant macrophage population in pulmonary fibrosis

Objectives This study evaluated the effects of low and moderate concentrations of triple antibiotic paste (TAP) and double antibiotic paste (DAP) loaded into a hydrogel system on crown discoloration and explored whether application of an adhesive bonding agent prevented crown discoloration. Materials and Methods Intact human molars (n = 160) were horizontally sectioned 1 mm apical to the cementoenamel junction. The crowns were randomized into 8 experimental groups (calcium hydroxide, Ca[OH]2; 1, 10, and 1,000 mg/mL TAP and DAP; and no medicament. The pulp chambers in half of the samples were coated with an adhesive bonding agent before receiving the intracanal medicament. Color changes (ΔE) were detected by spectrophotometry after 1 day, 1 week, and 4 weeks, and after 5,000 thermal cycles, with ΔE = 3.7 as a perceptible threshold. The 1-sample t-test was used to determine the significance of color changes relative to 3.7. Analysis of variance was used to evaluate the effects of treatment, adhesive, and time on color change, and the level of significance was p < 0.05. Results Ca(OH)2 and 1 and 10 mg/mL DAP did not cause clinically perceivable tooth discoloration. Adhesive agent use significantly decreased tooth discoloration in the 1,000 mg/mL TAP group up to 4 weeks. However, adhesive use did not significantly improve coronal discoloration after thermocycling when 1,000 mg/mL TAP was used. Conclusions Ca(OH)2 and 1 and 10 mg/mL DAP showed no clinical discoloration. Using an adhesive significantly improved coronal discoloration up to 4 weeks with 1,000 mg/mL TAP.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background and Objective Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD). Methods We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results. Results At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD ± 1.4) in the IMN 25mm YMPs (P Conclusions YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions.