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Understanding the function of the nasal vasculature in homeostasis and pathogenesis of common nasal diseases is important. Here we describe an extensive network of venous sinusoids (VSs) in mouse and human nasal mucosa. The endothelium of the VSs expressed Prox1 (considered to be a constitutive marker of lymphatic endothelium) and high levels of VCAM-1 and exhibited unusual cell-to-cell junctions. VSs are supported by circular smooth muscle cells (SMCs) and surrounded by immune cells. The nasal mucosa also showed a rich supply of lymphatic vessels with distinctive features, such as the absence of the lymphatic marker LYVE1 and sharp-ended capillaries. In mouse models of allergic rhinitis or acute Coronavirus Disease 2019 (COVID-19) infection, Prox1+ VSs were regressed or compromised. However, in aged mice, the VSs lost the SMC support and were expanded and enlarged. Our findings demonstrate three-dimensional morphological and molecular heterogeneities of the nasal vasculature and offer insights into their associations with nasal inflammation, infection and aging.

Chronic viral infections are often established by the exploitation of immune-regulatory mechanisms that result in nonfunctional T cell responses. Viruses that establish persistent infections remain a serious threat to human health. Sphingosine kinase 2 (SphK2) generates sphingosine 1-phosphate, which is a molecule known to regulate multiple cellular processes. However, little is known about SphK2’s role during the host immune responses to viral infection. Here, we demonstrate that SphK2 functions during lymphocytic choriomeningitis virus Cl 13 (LCMV Cl 13) infection to limit T cell immune pathology, which subsequently aids in the establishment of virus-induced immunosuppression and the resultant viral persistence. The infection of Sphk2-deficient (Sphk2(–/–)) mice with LCMV Cl 13 led to the development of nephropathy and mortality via T cell–mediated immunopathology. Following LCMV infection, Sphk2(–/–) CD4(+) T cells displayed increased activity and proliferation, and these cells promoted overactive LCMV Cl 13–specific CD8(+) T cell responses. Notably, oral instillation of an SphK2-selective inhibitor promoted protective T cell responses and accelerated the termination of LCMV Cl 13 persistence in mice. Thus, SphK2 is indicated as an immunotherapeutic target for the control of persistent viral infections.

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP‐competitive mitotic kinesin KIF18A inhibitor BTB‐1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB‐1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran‐binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB‐1 greatly improved the viability of IAV‐infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.

Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases., Graphical abstract, We found that non-invasive intratracheal administration of AAV2/8 targets pulmonary parenchymal cells, including AT2 cells. We used this system for the delivery of hACE2 to the lungs of various immune function-relevant gene KO mice and identified type I interferon signaling to create a protective effect against SARS-CoV-2 pathogenesis.

Highlights • RNA adjuvant was developed from the CrPV intergenic region IRES. • The RNA adjuvant functioned as an adjuvant with protein-based vaccines. • The RNA adjuvant increased vaccine efficacy and induced balanced Th1/Th2 response. • The RNA adjuvant enhanced APC chemotaxis., An ideal adjuvant should increase vaccine efficacy through balanced Th1/Th2 responses and be safe to use. Recombinant protein-based vaccines are usually formulated with aluminum (alum)-based adjuvants to ensure an adequate immune response. However, use of alum triggers a Th2-biased immune induction, and hence is not optimal. Although the adjuvanticity of RNA has been reported, a systematic and overall investigation on its efficacy is lacking. We found that single strand RNA (termed RNA adjuvant) derived from cricket paralysis virus intergenic region internal ribosome entry site induced the expression of various adjuvant-function-related genes, such as type 1 and 2 interferon (IFN) and toll-like receptor (TLR), T cell activation, and leukocyte chemotaxis in human peripheral blood mononuclear cells; furthermore, its innate and IFN transcriptome profile patterns were similar to those of a live-attenuated yellow fever vaccine. This suggests that protein-based vaccines formulated using RNA adjuvant function as live-attenuated vaccines. Application of the RNA adjuvant in mouse enhanced the efficacy of Middle East respiratory syndrome spike protein, a protein-subunit vaccine and human papillomavirus L1 protein, a virus-like particle vaccine, by activating innate immune response through TLR7 and enhancing pAPC chemotaxis, leading to a balanced Th1/Th2 responses. Moreover, the combination of alum and the RNA adjuvant synergistically induced humoral and cellular immune responses and endowed long-term immunity. Therefore, RNA adjuvants have broad applicability and can be used with all conventional vaccines to improve vaccine efficacy qualitatively and quantitively.

Dendrobium plants are the most important orchids used in horticultural industries and oriental medicine. Recently, several Dendrobium mutant genotypes with improved horticultural traits have been developed using various mutagens such as gamma irradiation, somaclonal variation, and aerospace mutagenesis. This study investigated genetic diversity and variations among 7 Dendrobium mutant genotypes and 11 commercial Dendrobium cultivars using single nucleotide polymorphism (SNP) markers generated from genotyping-by-sequencing (GBS) analysis. In addition, the SNPs were converted into a competitive allele-specific PCR (KASP) assay to discriminate the Dendrobium genotypes. A total of 67,669,394 clean data reads were generated, with 3.7 million reads per genotype on average, and 38,168,915 (56.4%) mapped reads. A total of 517,660 SNPs were detected, which included 443,305 homozygous and 74,355 heterozygous loci. The frequency of transition substitutions was shown to be higher than that of transversions, and the transition:transversion ratio is 1.34. A set of 37,721 filtered SNPs was used to perform a phylogenetic analysis, which showed that there were clear differences among the Dendrobium genotypes based on their species. A total of 18 SNPs were used for the development of KASP assay sets, of which 10 were successfully applied to distinguish among Dendrobium genotypes. This study demonstrated that the SNPs and KASP assay sets are an economically efficient tool for mutant screening and for selection of elite genotypes in Dendrobium breeding programs.

Most recently, severe acute respiratory syndrome coronavirus-2 has triggered a global pandemic without successful therapeutics. The goal of the present study was to define the antiviral effect and therapeutic action of blue light irradiation in SARS-CoV-2-infected cells. Vero cells were infected with SARS-CoV-2 (NCCP43326) or mock inoculum at 50 pfu/well. After blue light irradiation, the inhibitory effect was assessed by qPCR and plaque reduction assay. When Vero cells were irradiated to blue light ranging from 1.6 to 10 J cm-2 , SARS-CoV-2 replication was inhibited by up to 80%. The antiviral effect of blue light irradiation was associated with translation suppression via the phosphorylation of eIF2α by prolonging endoplasmic reticulum (ER) stress. The levels of LC3A/B and Beclin-1, which are key markers of autophagy, and the levels of PERK and PDI for ER stress were highly increased, whereas caspase-3 cleavage was inhibited after blue light irradiation in the later stage of infection. Our data revealed that blue light irradiation exerted antiviral and photo-biogoverning activities by prolonging ER stress and stimulating autophagy progression during viral infection. The findings increase our understanding of how photo-energy acts on viral progression and have implications for use in therapeutic strategies against COVID-19.

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120–159 mmHg or diastolic blood pressure 80–99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants’ diastolic blood pressure (−9.92 mmHg, p &lt, 0.001) and systolic blood pressure (−10.34 mmHg, 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.

Objectives: The present study was undertaken to investigate the relationship between acupuncture therapy and surgery rate. Design: Matched, retrospective cohort study. Materials and Methods: From nationwide health insurance data (2002–2013 cohort data published by the National Health Insurance Service of Korea), patients with new cases of knee osteoarthritis that occurred between January 1, 2004 and December 31, 2010 were analyzed. Patients were divided into an acupuncture group (AG) and a control group (CG), based on records of acupuncture therapy. Propensity scores were calculated by using gender, age, income level, and Charlson comorbidity index (CCI), with the groups matched at a ratio of 1:3 (AG:CG). The final analysis period was 2 years after the first acupuncture therapy for AG and 2 years after initial diagnosis for CG; surgery rates were compared between the two groups. Stratified analyses were performed based on age, gender, and income level; sensitivity analyses were performed based on the frequency and duration of acupuncture therapy. Results: Propensity score-matched AG and CG included 8,605 and 25,815 subjects, respectively. Post-matching surgery rates were 0.26 and 0.93% in AG and CG, respectively. For all age groups, AG showed a lower surgery rate than CG. In the analysis based on gender, the female group showed a significantly lower hazard ratio of 0.225. In analysis based on income level, the results of the entire group were significant, with the lower income group showing the lowest hazard ratio. In sensitivity analyses, AG tended to show a lower surgery rate than CG. Conclusions: The present study demonstrated that acupuncture therapy is associated with a low rate of surgery for knee osteoarthritis. Additional studies are needed to support this conclusion.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

Anthropomorphic animal face masking is the process where human characteristics are plotted on the animal kinds. The term anthropomorphic derived from anthropomorphism, which means displaying animals, gods, and other objects as if they are human in appearance, character, or behavior. In this research, we are proposing a compact automatic Control Point selection system based morphing process. Our compact system contains the Viola-Jones algorithm based Control Point selection system that detects facial features for the human face and takes the Control Points automatically. In addition, for the animal face Control Points, we made a predefined animal face set containing their corresponding Control Points. The whole process is done by firstly finding the Control Points and secondly, doing triangulation based morphing between the particular human face and the animal face. The simulation results demonstrate that the proposed morphing method produces less deformation and at the same time manages to complete the morphing process without any human assistance.

Background: Hypertension is a major cause of cardiovascular disease and associated mortality, and postmenopausal women are at a high risk of hypertension. We aim to investigate the hypotensive effect and safety of acupuncture, focusing on postmenopausal women with prehypertension and stage 1 hypertension. In addition, we aim to investigate whether the effect of acupuncture treatment differed, depending on Sasang Constitution and cold–heat pattern. Methods: This study is designed as an intervention cohort study. Two hundred postmenopausal women aged

Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine-induced humoral and cell-mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine-induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC-/- ) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine-immunized ASC-/- mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC-/- mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T-lymphocyte response against influenza vaccine was not induced in ASC-/- mice. Therefore, vaccinated ASC-/- mice did not show effective protection against viral challenge. ASC-/- mice immunized with alum-formulated HPV vaccine showed similar antibody titers and T-cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV-specific antibody titers in ASC-/- mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC-deficient condition.

An efficient protocol for asymbiotic seed germination and multiple shoot production of Thrixspermum japonicum has been established. Seeds were cultured on MSB (Murashige and Skoog, (MS) macro- and micro-nutrients, 0.1% (w/v) activated charcoal (AC), and 3.0% (w/v) sucrose) medium fortified with different concentrations of coconut water (CW), indole-3-acetic acid (IAA), or α-naphthaleneacetic acid (NAA), and gibberellic acid (GA3) to promote seed germination. The highest seed germination percentage (88.1%) was observed on MSB medium fortified with 0.2% (v/v) CW, 0.2 mg L−1 NAA and 0.5 mg L−1 GA3. Optimized shoot induction (94.3%) and maximum shoot numbers (8.3) were obtained on protocorm cultured on MS medium amended with 0.1% (w/v) AC, 3.0% (w/v) banana pulp, 2.0% (w/v) potato homogenate, 0.3 mg L−1 KN, 0.2 mg L−1 NAA, and 0.5 mg L−1 GA3. Rooting of the shoots was best achieved on MS medium supplemented with 0.1% (w/v) AC, 3.0% (w/v) banana pulp and 2.0% (w/v) potato homogenate, and 0.8 mg L−1 indole-3-butyric acid. Plantlets were acclimatized in the greenhouse with 88.1% survival rates. The protocol proposed in this study could be useful for conservation of S. japonicus, an important and rare epiphytic orchid.

The influence of 2,4-dichlorophenoxyacetic acid (2,4-D), benzyladenine (BA), and thidiazuron (TDZ) on direct rhizome induction and shoot formation from rhizome explants of Cymbidium goeringii was explored. Rhizome segments obtained from in vitro seed cultures of C. goeringii were placed on Murashige and Skoog (MS) medium incorporated with 5, 10, 20, or 40 µM 2,4-D and 1, 2, 4, or 8 µM BA or TDZ alone or in combination with 20 µM 2,4-D. The explants developed only rhizomes on MS medium with or without 2,4-D. The highest percent of rhizome formation (100%) was obtained on MS medium incorporated with 20 μM of 2,4-D. The morphology and number of rhizomes varied with the level of 2,4-D in the medium. Direct adventitious shoot formation was achieved on medium incorporated with BA or TDZ. The adventitious shoots produced per explant significantly increased with the supplementation of 2,4-D to cytokinin-containing medium. The highest mean of 21.8 ± 1.8 shoot buds per rhizome segment was obtained in medium fortified with 20 μM 2,4-D and 2 μM TDZ. The greatest percent of root induction (100%) and the mean of 5.3 ± 1.1 roots per shoot were achieved on ½ MS medium incorporated with 2 μM of α-naphthaleneacetic acid. About 97% of the in vitro-produced plantlets acclimatized in the greenhouse. An efficient in vitro propagation protocol was thus developed for C. goeringii using rhizome explants.

Graphical abstract, Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-β-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.

Object tracking is one of the well-known topic in Computer Vision sphere with challenging and problematic tasks that frames come with problems like overlapping, camera motion blur, changing object appearance, environmental variations and so on. Using OpenCV based CSRT (Channel and Spatial Reliability Tracking) tracker itself, without integration object detection part may face problems which mentioned above. To overcome that challenges we integrated deep learning based object detection with CSRT tracker and got better tracking results.

Objective: Surgical treatment of neck pain often entails high costs and adverse events. The present cohort study investigated whether utilisation of acupuncture in neck pain patients is associated with a reduced rate of cervical surgery. Methods: The Korean National Health Insurance Service National Sample Cohort (NHIS-NSC) database was retrospectively analysed to identify the 2 year incidence of cervical surgery in Korean patients suffering neck pain from 2004 to 2010. The incidence was calculated and compared between patients receiving and not receiving acupuncture treatment using Cox proportional hazards models. Cumulative survival rates were compared using Kaplan-Meier survival analysis. Results: The acupuncture and control groups included 50 171 and 128 556 neck pain patients, respectively. A total of 50 161 patients were selected in each group following propensity score matching with regard to sex, age, income and Charlson comorbidity index. The hazard ratio (HR) for surgery within 2 years was significantly lower in the acupuncture group compared with the control group (HR 0.397, 95% CI 0.299 to 0.527). In addition, subgroup analyses according to gender, age and income revealed consistent results for both men (HR 0.337, 95% CI 0.234 to 0.485) and women (HR 0.529, 95% CI 0.334 to 0.836); the results were consistently observed across all age and income strata. Sensitivity analysis with varying numbers of acupuncture treatments and treatment course duration also consistently indicated lower HRs for surgery within 2 years in the acupuncture group compared with the control group. Conclusions: A significantly lower HR for cervical surgery was observed in neck pain patients following acupuncture treatment. Acupuncture treatment may therefore be an effective method for managing neck pain, and has the potential to mitigate unnecessary surgery. These findings need to be confirmed by prospective studies.

The CDMA service coverage is split into different cells. If the available resource in a cell is not sufficient to supply the user's requirement, that cell becomes a hot-spot. As a result, the call will be clogged. The hot-spot causes the high blocking probability. Therefore, various methods including channel borrowing, cell overlaying, adaptive cell sectorization and so on, have been mentioned in many papers. In this paper, we proposed a beam reassignment method (BR) to diminish the call-blocking probability of one hot-beam and multi-service CDMA. A simulation result shows the effectiveness of the BR method in a hot-spot in two and three service-classes.

A total of 13,000 individuals of Dendrobium moniliforme (L.) Sw. artificially propagated in laboratories and greenhouses were restored in their natural habitat of Bogildo Island, Wandogun, in the southern part of Korea in June of 2013. The growing conditions of the individuals were monitored for two years. The parental individuals for the restoration were obtained from a wild population in southern Korea, from which seeds were produced via artificial crossings. These seeds were germinated and cultivated in growing media and two-year-old plants were then grown in greenhouse beds. The genetic diversity among the propagated individuals was confirmed by examining DNA sequences of five regions of the chloroplast genome and the nuclear ITS region. The diversity values were as high as the average values of natural populations. All propagated individuals were transplanted into two different sites on Bogildo by research teams with local residents and national park rangers. After restoration, we counted and measured the surviving individuals, vegetative propagated stems, and growth rates in June of both 2014 and 2015. There was no human interference, and 97% of the individuals survived. The number of propagules increased by 227% in two years. In contrast, the average length of the stems decreased during the period. In addition, different survival and propagation rates were recorded depending on the host plants and the restored sites. The shaded sides of rock cliffs and the bark of Quercus salicina showed the best propagation rates, followed by the bark of Camellia japonica. A few individuals of D. moniliforme successfully flowered, pollinated, and fruited after restoration. Overall, our monitoring data over two years indicate that the restored individuals were well adapted and vigorously propagated at the restored sites. In order to prevent human disturbance of the restored sites, a CCTV monitoring system powered by a solar panel was installed after the restoration. In addition, a human surveillance system is operated by national park rangers with local residents.

Background The two most common skin cancers are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The purpose of this study was to describe the detailed clinical behavior of BCC and SCC in the head and neck region over 19 years at a single institution. Methods A retrospective analysis was performed for all patients with non-melanoma skin cancer who had undergone surgical resection over an 18-year period. Patient charts were reviewed for demographic information, tumor size, onset-to-diagnosis, anatomic location, clinical subtype, histologic differentiation, method of surgical treatment, and recurrence. Results The review identified 265 cases of either BCC or SCC in 226 patients. Of the 226 patients, 80 (35.4%) were men and 146 (64.6%) were women. BCC (n=138, 55.9%) was more frequent than SCC (109, 44.1%). The most frequent age group was 70-to-79 year olds (45 patients, 35.2%) for BCC and 80-to-89 year olds (41 patients, 41.8%) for SCC. By aesthetic units of the face, the most common location was the nasal unit (44 cases, 31.9%) for BCC and the buccal unit (23 cases, 21.1%) for SCC. The most common clinical subtype of BCC was the nodular type (80 cases, 58.0%). Local flaps were most commonly used to cover surgical defects (136 cases, 55.1%). Recurrent rates were 2.2% for BCC and 5.5% for SCC. Conclusion In our study, many characteristics of BCC and SCC were compared to previously published reports were generally similar, except the ratio of BCC to SCC. Further study can help to establish the characteristics of BCC and SCC.

Segmentation of red blood cells (RBCs) and white blood cells (WBCs) in peripheral blood smear images plays an important role in the evaluation and diagnosis a vast of disorders, including infection, leukemia, and some types of cancer. Generally, various image processing techniques are used to enhance the quality of images before the segmentation step. Therefore, the segmentation of blood cells is still a challenge. However, in this research, deep learning semantic segmentation - cutting-edge technology is applied for segmentation red blood cells and white blood cells in blood smear images. The experiment result shows that the global accuracy of our model yielded 89.45%. Besides, the accuracy of the segmentation of white blood cells, red blood cells, and the background of blood smear image reached 94.93%, 91.11%, and 87.32%, respectively.

Cell counting remains a challenging task especially because of the extreme variation of the size and shape of the microscopy data. Conventional counting methods are mostly based on the utilization of the segmentation masks as the prior information for estimating the number of the cells in the image. We propose in this work a novel cell counting scheme that uses the features provided by a deep convolutional autoencoder (DCAE) as the inputs of a shallow regressor network, instead of using the segmentation masks. First, the cellular image is given to the DCAE whose task is to reconstruct the original input image with an encodingdecoding scheme. The latent representations located in the middle of the DCAE are extracted and used as the final feature representation of the images. The second step consists of using these features as the inputs of a neural network based regressor whose outputs will represent the number of the cells in the image. The results demonstrate how the proposed scheme really manages to recognize the exact number of the cells even in the case of significant overlapping situations, exactly where most of the state-of-the-art cell counting methods fail.

Background Traumatic brain injury(TBI) is one of the major causes of death and disability in children. Understanding epidemiologic characteristics of TBI in children is the first step for developing preventative strategies, optimizing care systems and rehabilitation of injury. Aims We aimed to describe and compare epidemiologic features and outcomes among children with TBI according to aged groups. Methods This is a cross-sessional study based on the date of the Emergency Department(ED)–based Injury In-depth Surveillance (EDIIS) in Korea. EDIIS is a prospective injury registry and total 23 EDs in tertiary hospital participate in it. We identified children (aged 0 to 18) with TBI in EDs between Jan. 2011 and Dec. 2015. We classified children into two aged categories: pre-school group (under 7 years old) and school-aged group (7 years old and over). Results During the study period (5 years), a total of 30 866 children with TBI were included in the analysis. There were 19 231 patients (62.3%) in pre-school group and 11 635 patients (37.7%) in school-aged group. TBI in school-aged group occurred more in male, road and school/educational facilities, recreational and educational activities, daytime and weekday compared with pre-school group (all p value Discussion and conclusions The epidemiological characteristics of TBI in school-aged group are differentiated from pre-school group and rate of mortality and intracranial injuries in school-aged group were higher. It is necessary to develop differentiated preventative strategies and treatment systems according to aged groups in children.

El titanio es ampliamente utilizado como implante dental dado que es bioinerte y osteointegrable. Sin embargo, dado que este material no puede inducir el crecimiento de hueso desde su superficie, es usual que se le realicen distintos tratamientos superficiales para desarrollar recubrimientos bioactivos. El tratamiento alcalino tiene por objetivo formar un gel de titanato de sodio amorfo, el cual se puede estabilizar, por medio de un tratamiento térmico posterior. Durante este último, el hidrogel se deshidrata y se densifica para formar una capa de titanato de sodio estable y parcialmente cristalizado. En el presente trabajo se analizaron los efectos producidos por diferentes tratamientos térmicos posteriores al alcalino, sobre superficies de titanio cp con tratamiento superficial de blastinizado y APQ (anodizado por plasma químico). Para cada caso se caracterizó la superficie con el fin de optimizar la condición de aplicación. Las temperaturas de los tratamientos térmicos fueron 400, 600 y 800 ºC, dado que en este rango el titanato varía su proporción de fase amorfa y cristalina y por ende sus propiedades. La evaluación de los resultados se realizó mediante ensayos de adhesión Rockwell C, medición del ángulo de contacto inicial por goniometría, difracción de rayos x, SBF y microscopia electrónica de barrido. Caracterizadas las probetas post tratamiento térmico se pudo observar que, las muestras tratadas a 800 ºC presentaron una estructura superficial cristalina, mala adhesión y no indujeron crecimiento de apatita sobre su superficie. No obstante presentaron una superficie hidrofilica. Por otro lado, las muestras tratadas a 400 y 600 ºC presentaron superficialmente una fase parcialmente cristalizada, con buena adherencia y buena hidrofilicidad. Mediante SEM-EDS, se observó sobre sus superficies la formación de una capa de apatita homogénea., Titanium is widely used as dental implant since it is bio-inert and osseointegratable. However, provided that this material cannot induce bone growth from its surface, it is usual to carry out different surface treatments in order to develop bioactive coatings that increase both the initial rate of bone development and the biological anchorage of implant attachment to the host bone. The aim of the alkaline treatment is to form an amorphous gel of sodium titanate, which can be stabilized by means of a subsequent thermal treatment. During this, the hydro gel is dehydrated and thickened to form a layer of stable and partially crystallized sodium titanate. In the present work it was analyzed the effects produced by different thermal treatments after the alkaline one, on surfaces of cp titanium with surface treatment of blasting and MAO (micro-arc oxidation pro-cess). For each case the surface was characterized in order to enhance the application condition. The temper-ature of the thermal treatments was 400, 600 and 800 ºC, since titanate varies its ratio of amorphous and crys-talline phase in this range and therefore its properties. The assessment of results was carried out by means of Rockwell-C adhesion standard test, measurement of the initial contact angle by goniometry, X-ray diffraction and analytic scanning electronic microscopy. Characterized post thermal treatment samples, it was observed that the samples treated to 800 ºC presented a crystalline superficial structure, bad adherence and did not develop apatite growth on its surface. Neverthe-less, they presented sufficiently surface hydrophilic. On the contrary, the samples treated at 400 and 600 ° C presented superficially a partially crystallized phase, with good adhesion and good hydrophilicity. Through SEM-EDS, the formation of a homogeneous apatite layer was observed on their surfaces., Facultad de Ingeniería, Comisión de Investigaciones Científicas de la provincia de Buenos Aires

Recently, the public has developed a growing interest in aesthetic surgery. Middle-aged individuals in Northeastern Asia have have shown particular interest in undergoing blepharoplasty to reduce bulging eyelid fat. However, those who present for aesthetic surgery usually have not considered the possibility of an eyelid tumor, and thus, have not taken time to undergo evaluation for this possibility. Here, the authors describe a case of mucosaassociated lymphoid tissue (MALT) lymphoma that was diagnosed by a thorough physical examination in a man requesting lower blepharoplasty. A 58-year-old man visited out aesthetic center to alleviate bulging of both lower eyelids, which had begun approximately 5 years previously. The patient had no underlying disease at presentation, and chest X-ray and electrocardiography findings were normal. Physical examination confirmed bulging of both lower eyelids to a similar extent, and the unidentified tumor was palpated on the left side (Fig. 1). A biopsy was recommended for evaluation purposes, but the patient requested cosmetic surgery only, and thus, we began lower blepharoplasty after informing the patient that a biopsy might be needed during surgery and that if so, additional treatment might be required. Initially, we elevated a musculocutaneous flap by subciliary incision, and then began dissection to the extent of the inferior orbital rim. After exposing the preseptal space, an incision was performed on the orbital septum to expose the orbital fat for removal and transposition. However, we encountered a pinkish, hard, highly vascularized mass-like lesion between the orbital septum and orbital fat, which is not normally found during lower blepharoplasty. After resecting the 1.8 cm × 1.5 cm × 1.2 cm mass, lower blepharoplasty was performed in the usual manner (Fig. 2). The pathologic examination result indicated MALT lymphoma with an immunoprofile of CD20 (+), bcl-2 (+), CD3 (–), CD10 (–), CD38 (–), and CD138 (–) (Fig. 3). The patient was sent to another hospital for a systematic workup, and subsequent orbital computed tomography (CT) and positron emission tomography (PET)-CT indicated a possibility of residual lymphoma localized in the extraocular area (Fig. 4). As a result, he was treated using involved-field radiation therapy at the origin of the lymphoma at 2 Gy for 20 days based on a 1AE Ann Arbor staging. Orbital CT and PET-CT at 6 months postoperatively revealed no evidence of lymphoma and a good cosmetic outcome was achieved at 6 months after surgery (Fig. 5). The patient was very satisfied with the discovery of the mass at an early stage and the sufficient biopsy.

We investigated whether the lack of galactosyltransferase (α-Gal) expression in bone tissue is associated with reduced immune response of human peripheral blood mononuclear cells (PBMCs) against pig bone tissue. When human PBMC obtained from heparinized blood of healthy volunteers was stimulated with bone extracts of pigs withα-1,3-galactosyltransferase knock out (α-Gal KO), the proliferation of human PBMCs and production of proinflammatory cytokines such as TNF-αand IL-1βwere significantly reduced compared to those stimulated with bone extracts of wild type (WT) pigs. In addition, activation of CD4+helper T cells and production of IL-2, IFN-γ, and IL-17 were reduced upon stimulation with bone tissue extracts fromα-Gal KO pigs. This is possibly due to the lowered activities of the NF-κB, p38, ERK, and JNK signaling pathways. Our findings can be used to evaluate the compatibility of bone tissues fromα-Gal KO pigs with human bone grafting as novel natural biomaterials, thereby increasing the feasibility of future clinical applications.

Highlights • Immunization with MERS spike protein nanoparticles induced only Th2-biased response. • Heterologous prime-boost immunization induced both Th1 and Th2-biased responses. • Our vaccination strategy showed the protective effect against MERS-CoV., The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime–boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime–boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime–boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime–boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime–boost regimens did not. Thus, heterologous prime–boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime–boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

El presente trabajo de tesis se enmarca en el estudio de biomateriales implantables de titanio y acero inoxidable con diferentes tratamientos superficiales con el propósito de desarrollar métodos y estrategias de caracterización superficial, analizando los parámetros que caracterizan cada tratamiento o conjunto de tratamientos a través de técnicas espectroscópicas y microscopía electrónica de barrido. Los resultados obtenidos fueron correlacionados con ensayos de microdureza, adhesión y/o polarización potenciodinámica cíclica. Vale destacar que la mejor combinación de técnicas para caracterizar un biomaterial implantable dependerá del tipo de material, del tratamiento superficial que tenga y de la función que cumplirá como implante. Contar con métodos confiables para caracterizar daños por corrosión y/o tribocorrosión en diversos tipos de componentes y especialmente en implantes ortopédicos, resulta imprescindible para mejorar la calidad y asegurar la integridad de los mismos. Por ello, resulta de gran utilidad disponer de una herramienta de caracterización confiable de pits de corrosión mediante microscopía electrónica de barrido (SEM), ya que la corrosión por picado es un mecanismo de daño muy común y pernicioso en biomateriales y el SEM es una técnica hoy día muy versátil y accesible para el estudio de biomateriales. En este sentido, se evaluaron los errores en las mediciones topográficas en muestras de acero inoxidable 316LVM (Low Vacuum Melting) (ASTM F138 y F139/ISO 5832-1) con diferentes tratamientos superficiales, como el blastinizado (en inglés, blasting) y el pasivado químico, mediante el uso de pares estéreos de imágenes de microscopio electrónico; y los resultados fueron cotejados con mediciones electroquímicas. La caracterización de la topografía superficial es fundamental en los biomateriales ya que determina el desempeño de los implantes, sobre todo de los dentales. Una de las maneras ampliamente utilizadas para caracterizar la topografía es a partir de la rugosidad. La rugosidad de una superficie se describe apelando a distintos conjuntos de parámetros, entre los cuales se encuentran los funcionales y los de amplitud. La utilidad de cada parámetro es motivo de estudio en el abordaje de una nueva aplicación y la correcta elección de los parámetros más significativos depende de las características del tratamiento superficial utilizado y del objetivo del estudio realizado. De acuerdo con lo expresado, se estudiaron superficies de aceros inoxidables 316LVM (Low Vacuum Melting) (ASTM F138 y F139/ISO 5832-1) y de titanio c.p. ASTM Grado 4 sometidas a diversos tipos de tratamientos -dentro de los cuales se encuentran el mecanizado, blastinizado, anodizado por plasma químico y pasivado químico. Estos estudios se realizaron a partir del análisis de los parámetros de rugosidad obtenidos mediante la técnica de pares estéreos de imágenes de microscopía electrónica de barrido, en combinación con ensayos de microdureza, adhesión y polarización potenciodinámica cíclica. Finalmente, debido a que los implantes de titanio y sus aleaciones presentan diferentes capas superficiales de óxidos que pueden optimizar el desempeño de estos biomateriales, se desarrolló un método para determinar espesores de óxido de titanio en el intervalo de interés de los implantes dentales y ortopédicos a partir de espectros de rayos X obtenidos mediante la técnica de microanálisis con sonda de electrones. Para el estudio de las capas de óxido generadas mediante anodizado, la intensidad de la línea característica Kα del oxígeno fue relacionada con el espesor correspondiente. Debido a una alteración local del material causada por el haz de electrones, fue necesario efectuar una recalibración mediante la técnica de espectroscopía de retrodispersión de Rutherford., Facultad de Ingeniería

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; 1 × 10⁸ CFU/mouse) or high dosage (JW15-H; 1 × 10⁹ CFU/mouse), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Twomonth- old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-γ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.

Thin film thickness can be readily associated to the X-ray intensities emitted under electron bombardment. The aim of this work is to develop a method for measuring titanium oxide thicknesses in biomaterials from the X-ray spectra induced in a scanning electron microscope. The oxide layers studied were generated with different anodizing voltages applied in phosphoric and boric acid solution (H3PO4/H3BO3). The oxygen Kα intensity was registered for each sample and related to the corresponding thickness. In order to account for local material alterations, a recalibration is shown to be necessary; Rutherford backscattering spectroscopy was used at this stage. The method is useful for TiO2 thicknesses in the range of interest for dental and orthopedic implants (10–100 nm), and it could be extended to greater thicknesses by adequately selecting the electron beam energy. Fil: Kang, Kyung Won. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina Fil: Limandri, Silvina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Castellano, Gustavo Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Suarez, Sergio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Trincavelli, Jorge Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina