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We investigated the association between obesity and cardiovascular disease risk factors (CVDRFs) in adolescents. We performed a cross-sectional study using the data from 8149 adolescents, aged 10–18 years, included in the Korean National Health and Nutrition Examination Survey (2011–2020). Using the body mass index, we defined “overweight” (≥85th to

Perianal fistulizing diseases, namely perianal fistulas and/or abscesses, are well-known complications of Crohn's disease (CD). These are known to develop more frequently in Asian children with CD, especially in the early stages of the disease course. Approximately half of the pediatric CD cases in Korea present with perianal fistulizing diseases at diagnosis. We report a rare case of a 12-year-old boy with CD with an incidental discovery of a perianal abscess on pelvic magnetic resonance imaging during CD diagnosis. No symptoms or signs of perianal fistulizing disease were identified. The early diagnosis of the perianal abscess enabled timely and effective treatment. Considering the high incidence of concomitant perianal CD in Korean children at diagnosis, perianal imaging may be useful and should be considered during diagnostic evaluation, even in patients with no subjective or objective findings indicating perianal CD.

Objectives: Pneumothorax and pneumomediastinum are associated with high mortality in invasively ventilated coronavirus disease 2019 (COVID-19) patients; however, the mortality rates among non-intubated patients remain unknown. We aimed to analyze the clinical features of COVID-19-associated pneumothorax/pneumomediastinum in non-intubated patients and identify risk factors for mortality. Methods: We searched PubMed Scopus and Embase from January 2020 to December 2021. We performed a pooled analysis of 151 patients with no invasive mechanical ventilation history from 17 case series and 87 case reports. Subsequently, we developed a novel scoring system to predict in-hospital mortality; the system was further validated in multinational cohorts from ten countries (n = 133). Results: Clinical scenarios included pneumothorax/pneumomediastinum at presentation (n = 68), pneumothorax/pneumomediastinum onset during hospitalization (n = 65), and pneumothorax/pneumomediastinum development after recent COVID-19 treatment (n = 18). Significant differences were not observed in clinical outcomes between patients with pneumomediastinum and pneumothorax (±pneumomediastinum). The overall mortality rate of pneumothorax/pneumomediastinum was 23.2%. Risk factor analysis revealed that comorbidities bilateral pneumothorax and fever at pneumothorax/pneumomediastinum presentation were predictors for mortality. In the new scoring system, i.e., the CoBiF system, the area under the curve which was used to assess the predictability of mortality was 0.887. External validation results were also promising (area under the curve: 0.709). Conclusions: The presence of comorbidity bilateral pneumothorax and fever on presentation are significantly associated with poor prognosis in COVID-19 patients with spontaneous pneumothorax/pneumomediastinum. The CoBiF score can predict mortality in clinical settings as well as simplify the identification and appropriate management of patients at high risk.

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(−) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(−) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499–15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT.

We previously reported the potent antiviral effect of the 2-aminoquinazolin-4-(3H)-one 1, which shows significant activity (IC50 = 0.23 μM) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with no cytotoxicity. However, it is necessary to improve the in vivo pharmacokinetics of compound 1 because its area under the curve (AUC) and maximum plasma concentration are low. Here, we designed and synthesized N-substituted quinazolinone derivatives that had good pharmacokinetics and that retained their inhibitory activity against SARS-CoV-2. These compounds were conveniently prepared on a large scale through a one-pot reaction using Dimroth rearrangement as a key step. The synthesized compounds showed potent inhibitory activity, low binding to hERG channels, and good microsomal stability. In vivo pharmacokinetic studies showed that compound 2b had the highest exposure (AUC24h = 41.57 μg∙h/mL) of the synthesized compounds. An in vivo single-dose toxicity evaluation of compound 2b at 250 and 500 mg/kg in rats resulted in no deaths and an approximate lethal dose greater than 500 mg/kg. This study shows that N-acetyl 2-aminoquinazolin-4-(3H)-one 2b is a promising lead compound for developing anti-SARS-CoV-2 agents.

Sound event localization and detection (SELD) is a joint task that unifies sound event detection (SED) and direction-of-arrival estimation (DOAE). The task has become such a popular topic that it was introduced into the challenge on Detection and Classification of Acoustic Scenes and Events (DCASE) Task3 in 2019. In this paper, we propose a method based on dual cross-modal attention (DCMA) and parameter sharing to simultaneously detect and localize sound events. In particular, the DCMA-based decoder commonly used for multiple predictions efficiently learns the associations between SED and DOAE features by exchanging SED and DOAE information in the process of attention, in addition to the encoder with parameter sharing. Furthermore, acoustic features that have not been usually used in the SELD task are additionally adopted to improve the performance, and data augmentation techniques of the mixup to simulate polyphonic events and channel rotation for spatial augmentation are conducted for this task. Experimental results demonstrate that our efficient model using one common decoder block based on the DCMA to predict multiple events in the track-wise output format is effective for the SELD task with up to three overlapping events.

Buoyancy-aided unmanned aerial vehicle (UAV) has a powerful advantage in terms of flight time and safety, compared to conventional multirotors. However, previously developed platforms showed limited flight maneuverability (i.e. omnidirectional translation) and posture transition (i.e. omniorientational rotation) owing to lack of number of actuators or limit of design specifications. As a solution, this study presents a symmetric torus blimp, which is pierced in the middle of envelope and surrounded by four tiltable actuator. All flight-aid electric parts are located in the center of the hole to match center of buoyancy with center of mass. And four motors mounted along the edge of the hull can be tilted by each linked servo. Owing to symmetric design and sufficient number and allocation of actuators, stable independent omniorientational and omnidirectional motion during flight that standard blimp or multirotors hard to do can be easily performed. This performance can be achieved by simple feedback control algorithm based on aerodynamic model. Also, a novel control allocation based on a fully-actuated system is described for independent orientation and position control. The result of various angle tracking orientation control and stabilization control experiments performed are presented. In addition, omnidirectional control with manual control keeping orientation independently is validated. Finally, narrow space passing and omnidirectional wall interaction results are described to demonstrate the advantages of the specification of this platform.

The rhizome of Dryopteris crassirhizoma Nakai. (Dryopteridaceae) has been used in traditional medicine in East Asia and has recently been reported to have anticancer, anti-inflammation, and antibacterial activity as well as antiviral activity. Natural phloroglucinols from D. crassirhizoma, dryocrassin ABBA and filixic acid ABA were reported to inhibit influenza virus infection with an inhibitory activity on neuraminidase. In this study, we found that dryocrassin ABBA and filixic acid ABA have an inhibitory activity against the main protease of SARS-CoV-2. Therefore, dryocrassin ABBA and filixic acid ABA exhibited inhibitory activity against SARS-CoV-2 infection in Vero cells dose-dependently using the immunofluorescence-based antiviral assays. Moreover, these compounds inhibited SARS-CoV and MERS-CoV infection, suggesting their broad-spectrum anticoronaviral activity. In addition, a 5-day repeated-dose toxicity study of dryocrassin ABBA and filixic acid ABA suggested that an approximately lethal dose of these compounds in mice was >10 mg/kg. Pharmacokinetic studies of dryocrassin ABBA showed good microsomal stability, low hERG inhibition, and low CYP450 inhibition. In vivo pharmacokinetic properties of dryocrassin ABBA showed a long half-life (5.5–12.6 h) and high plasma exposure (AUC 19.3–65 μg·h/mL). Therefore, dryocrassin ABBA has therapeutic potential against emerging coronavirus infections, including COVID-19.

Background: Radiographic modalities have been commonly used to evaluate pectus carinatum (PC), and compressive orthotic bracing is the most widely accepted treatment method. The aim of this study was to determine the efficacy of 3-dimensional (3D) body surface scanning as an alternative modality for the evaluation of PC.Methods: The medical records of 63 patients with PC who were treated with compres-sive orthotic bracing therapy between July 2017 and February 2019 were retrospectively analyzed. Using both 2-view chest radiography (posteroanterior and lateral view) and 3D body scanning, the height of maximal protrusion of the chest wall was measured both be-fore and after 2 weeks of bracing therapy. The difference between the pre- and post-treat-ment measurements was calculated for both modalities, and these differences were com-pared and analyzed.Results: Based on the comparison between the pre- and post-treatment radiographs, bracing therapy produced favorable outcomes in all patients (p

The highly engineerable scattering properties of resonant optical antennas underpin the operation of metasurface-based flat optics. Thus far, the choice of antenna has been limited to shaped metallic and high-index semiconductor nanostructures that support geometrical plasmonic or Mie resonances. Whereas these resonant elements offer strong light–matter interaction and excellent control over the scattering phase and amplitude, their electrical tunability has proven to be quite limited. Here, we demonstrate how excitonic resonances in atomically thin semiconductors can be harnessed as a different, third type of resonance to create mutable, flat optics. These strong materials-based resonances are unmatched in their tunability with various external stimuli. To illustrate the concept, we first demonstrate how excitons can enhance the focusing efficiency of a millimetre-scale, patterned WS2 zone plate lens. We also show how electrical gating can completely turn on and off the exciton resonance and thereby modulate the focusing efficiency by 33%. By harnessing the excitonic resonances of a monolayer of WS2 in the visible spectral range, large-area, actively tunable and atomically thin optical lenses can be realized.

Objective The National Early Warning Score (NEWS), based on the patients’ vital signs, detects clinical deterioration in critically ill patients and is used to reduce the incidence of in-hospital cardiac arrest. However, although mortality prediction based on vital signs may be difficult in older patients, the effectiveness of the NEWS has not yet been evaluated in this population. This study aimed to test the hypothesis that an elevated NEWS at admission increases the mortality risk in older patients admitted to the emergency department (ED). Methods We conducted a single-center retrospective study, including patients admitted to the ED between November 2016 and February 2017. We included patients aged >65 years who were admitted to the ED for any medical problem. The NEWS was calculated at the time of ED admission. The primary outcome was in-hospital mortality. Results In total, 3,169 patients were included in this study. Median age was 75 years (interquartile range [IQR], 70 to 80 years), and 1,557 (49.1%) patients were male. The in-hospital mortality rate was 5.1% (161 patients). Median NEWS was higher in non-survivors than in survivors (5 [IQR, 3–8] vs. 1 [IQR, 0–3], P65 years.

Background and Aim: There is paucity of data regarding the epidemiology of pediatric IBD in Asia compared to that of Western countries. We aimed to investigate the incidence and prevalence trends of pediatric inflammatory bowel disease (IBD) in the Daegu-Kyungpook province of South Korea from 2017 to 2020.Methods: This study was a multicenter, retrospective study conducted in eight IBD referral centers located in the Daegu-Kyungpook province. Children and adolescents of ≤18 years who were initially diagnosed with IBD between 2017 and 2020 were included. The annual number of children and adolescents newly diagnosed with IBD and the annual resident population of children and adolescents ≤18 years of age in the Daegu-Kyungpook province were investigated to calculate the annual incidence and prevalence in the region.Results: A total 304 children and adolescents that had been diagnosed with IBD were included in this study. Among these patients, 71.4% had been diagnosed with Crohn's disease (CD), and 28.6% with ulcerative colitis (UC). The population based annual incidences of IBD from 2017 to 2020 were each 7.24, 6.82, 10.27, and 13.33 per 100,000, respectively (P for trend P for trend P for trend = 0.174).Conclusion: Pediatric IBD, especially CD has significantly increased recently in the Daegu-Kyungpook province. Epidemiology studies from other regions of Asia are required to better elucidate this trend of increase in Asia.

Objectives: To date, there is no consensual definition of what constitutes a postoperative recurrence of primary spontaneous pneumothorax (PSP), despite there being many studies reporting a high incidence of recurrence. This study aims to describe the long-term recurrence rates of pneumothorax and to suggest a possible way to differentiate recurrence events based on temporal patterns. Methods: This single-center study retrospectively evaluated all postoperative recurrence of PSP from January 2007 to May 2019. Patients’ demographics, history of pneumothorax, radiologic data, surgical technique, and the time between operation and recurrence were analyzed. Univariate and multivariable analyses were conducted to find potential risk factors related to long-term recurrence. Results: Of the 77 postoperative recurrent cases of pneumothorax, 21 (27.2%) occurred within 30 days after surgery and, thus, were classified as early recurrences (ER), while the remaining cases were classified as late recurrences (LR). There was no difference in preoperative variables between the two groups. However, the rate of incidence of second recurrence (SR), which represented a long-term prognosis, was significantly higher in the LR group (28.6% vs. 4.8%, p = 0.030). On univariate and multivariable analyses, late recurrence was the only significant factor predicting later recurrence events. Conclusion: Postoperative recurrence (PoR) within 30 days had a lower SR rate. Therefore, it might not be a ‘true’ postoperative recurrence with a favorable prognosis. Further studies investigating postoperative recurrence based on temporal patterns would be warranted to improve the classification of PoR.

Cardiotonic steroids are steroid-like natural compounds known to inhibit Na+/K+-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells. Bufalin, cinobufagin, and telocinobufagin showed high anti-MERS-CoV activities (IC50, 0.017~0.027 μM), bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC50, 0.016~0.019 μM), cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC50, 0.231~1.612 μM). Differentially expressed genes in Calu3 cells treated with cinobufagin, telocinobufagin, or bufalin, which had high antiviral activity during MERS-CoV infection were analyzed using QuantSeq 3′ mRNA-Seq analysis and data showed similar gene expression patterns. Furthermore, the intraperitoneal administration of 10 mg/kg/day bufalin, cinobufagin, or digitoxin induced 100% death after 1, 2, and 4 days in 5-day repeated dose toxicity studies and it indicated that bufalin had the strongest toxicity. Pharmacokinetic studies suggested that telocinobufagin, which had high anti-coronavirus activity and low toxicity, had better microsomal stability, lower CYP inhibition, and better oral bioavailability than cinobufagin. Therefore, telocinobufagin might be the most promising cardiotonic steroid as a therapeutic for emerging coronavirus infections, including COVID-19.

Metasurface-based optical elements typically manipulate light waves by imparting space-variant changes in the amplitude and phase with a dense array of scattering nanostructures. The highly localized and low optical-quality-factor (Q) modes of nanostructures are beneficial for wavefront shaping as they afford quasi-local control over the electromagnetic fields. However, many emerging imaging, sensing, communication, display and nonlinear optics applications instead require flat, high-Q optical elements that provide substantial energy storage and a much higher degree of spectral control over the wavefront. Here, we demonstrate high-Q, non-local metasurfaces with atomically thin metasurface elements that offer notably enhanced light–matter interaction and fully decoupled optical functions at different wavelengths. We illustrate a possible use of such a flat optic in eye tracking for eyewear. Here, a metasurface patterned on a regular pair of eye glasses provides an unperturbed view of the world across the visible spectrum and redirects near-infrared light to a camera to allow imaging of the eye. High optical-quality-factor, non-local metasurfaces enable independent functions across different wavelength bands.

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations on OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p &lt, 0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralization), as well as providing additional space for new bone formation by rapid resorption.

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations of OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p

We address representation learning for large-scale instance-level image retrieval. Apart from backbone, training pipelines and loss functions, popular approaches have focused on different spatial pooling and attention mechanisms, which are at the core of learning a powerful global image representation. There are different forms of attention according to the interaction of elements of the feature tensor (local and global) and the dimensions where it is applied (spatial and channel). Unfortunately, each study addresses only one or two forms of attention and applies it to different problems like classification, detection or retrieval. We present global-local attention module (GLAM), which is attached at the end of a backbone network and incorporates all four forms of attention: local and global, spatial and channel. We obtain a new feature tensor and, by spatial pooling, we learn a powerful embedding for image retrieval. Focusing on global descriptors, we provide empirical evidence of the interaction of all forms of attention and improve the state of the art on standard benchmarks.

Aim: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. Methods: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. Results: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% ( n = 43/77) achieved a clinical response and 18.2% ( n = 14/77) achieved clinical remission. At week 14, 73.2% ( n = 52/71) achieved a clinical response and 39.4% ( n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% ( n = 43/105) and 49.5% ( n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). Conclusions: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

Purpose We assessed the clinical outcomes of a seton procedure combined with early versus late institution of infliximab (IFX) therapy. Methods This retrospective study comprised 76 patients who underwent surgery for perianal fistula associated with Crohn disease between January 2014 and November 2017. All patients underwent loose seton drainage combined with IFX therapy. Patients categorized as the early group (EG, 49 patients) received IFX therapy within 30 days of completion of the seton procedure. Patients categorized as the late group (LG, 27 patients) received IFX therapy >30 days after the seton procedure. IFX therapy was administered as induction and maintenance therapy. Results There were no statistically significant intergroup differences in clinical characteristics of the patients. The mean follow-up was 21.0 ± 11.6 months in the EG and 34.5 ± 18.4 months in the LG (P = 0.001). The mean interval between seton procedure and IFX induction therapy was 12.2 days in the EG and 250.2 days in the LG (P = 0.002). Complete remission was observed in 32 patients (65.3%) in the EG and 17 patients (63.0%) in the LG (P = 0.844). Fistula recurrence was observed in 6 patients (7.9%). All recurrences occurred in a previous perianal fistula tract. Conclusion Patients showed a good response to a seton procedure combined with IFX therapy regardless of the time of initiation of IFX therapy.

Objective Community-acquired pneumonia (CAP) is a major cause of sepsis, and sepsis-related acute organ dysfunction affects patient mortality. Although the quick Sequential Organ Failure Assessment (qSOFA) is a new screening tool for patients with suspected infection, its predictive value for the mortality of patients with CAP has not been validated. Lactate concentration is a valuable biomarker for critically ill patients. Thus, we investigated the predictive value of qSOFA with lactate concentration for in-hospital mortality in patients with CAP in the emergency department (ED). Methods From January 2015 to June 2015, 443 patients, who were diagnosed with CAP in the ED, were retrospectively analyzed. We defined high qSOFA or lactate concentrations as a qSOFA score ≥2 or a lactate concentration >2 mmol/L upon admission at the ED. The primary outcome was all-cause in-hospital mortality. Results Among the 443 patients, 44 (9.9%) died. Based on the receiver operating characteristic (ROC) analysis, the areas under the curves for the prediction of mortality were 0.720, 0.652, and 0.686 for qSOFA, CURB-65 (confusion, urea, respiratory rate, blood pressure, and age), and Pneumonia Severity Index, respectively. The area under the ROC curve of qSOFA was lower than that of SOFA (0.720 vs. 0.845, P=0.004). However, the area under the ROC curve of qSOFA with lactate concentration was not significantly different from that of SOFA (0.828 vs. 0.845, P=0.509). The sensitivity and specificity of qSOFA with lactate concentration were 71.4% and 83.2%, respectively. Conclusion qSOFA with lactate concentration is a useful and practical tool for the early prediction of in-hospital mortality among patients with CAP in the ED.

Purpose Inflammatory bowel disease (IBD) in Korea has been increasing in recent years, but accurate statistics about operations for IBD are lacking. The purpose of this study was to investigate the trends and current status of IBD surgeries in Korea. Methods Using a national database from the Korea Health Insurance Review and Assessment Service, we analyzed data from patients who underwent surgery for Crohn disease and ulcerative colitis from January 2009 to October 2016. Results The mean number of patients who underwent surgery for Crohn disease was 791.8 per year. Colorectal surgery, small bowel surgery, and anal surgery were performed fairly often (31.2%, 29.4%, 39.4%, respectively), and laparoscopic surgery continued to increase, recently exceeding 30%. About 50% of Crohn patients used biologics before and after surgery, and those patients also underwent a relatively high rate of anal surgeries (44.2%). The mean number of patients who underwent surgery for ulcerative colitis was 247.6 per year. Colorectal surgery accounted for more than half of all operations, and laparoscopic surgery has been increasing rapidly, having been performed in about 60% of patients in recent years. The incidence of colorectal cancer in patients with ulcerative colitis was very high and increased rapidly during the study period, reaching about 80%. Conclusion The number of patients undergoing laparoscopic surgery for IBD in Korea has increased significantly. Biologics are actively used by patients with Crohn disease, with a high proportion of anal surgeries required. Many of the surgical indications for ulcerative colitis have shifted into colorectal cancer.

Despite the numerous studies on melatonin and nicotinamide (NAM, the active form of vitamin B3), the linkage between these two biomolecules in the context of signaling pathways regulating preimplantation embryo development has not yet been investigated. In this study, we used bovine oocyte model to elucidate the effect of melatonin on the developmental competence of oocytes under the stress of high NAM concentrations. Results showed that NAM (20 mM) administration during in vitro maturation (IVM) significantly reduced oocyte maturation and actin distribution, while induced reactive oxygen species (ROS) accumulation and mitochondrial dysfunction, the multiple deleterious effects that were alleviated by melatonin (10−7 M). The RT-qPCR and/or immunofluorescence showed upregulation of the apoptosis (Caspase-3, Caspase-9, and BAX), autophagy (Beclin-1, LC3A, LC3B, ATG7, LAMP1, and LAMP2), cell cycle (P21, P27, and P53), and DNA damage (COX2 and 8-OxoG) specific markers in oocytes matured under NAM treatment, compared to NAM-melatonin dual-treated and the untreated ones. In addition, the total cleavage and blastocyst development rate, as well as the total number of cells and the inner cell mass (ICM) per blastocyst, were reduced, while DNA fragmentation was induced, in the group of NAM sole treatment than NAM-melatonin cotreatment and control. Inspecting the underlying mechanisms behind NAM-associated toxicity revealed an increase in transcription pattern of NAM methylation (NNMT and AHCY) genes in NAM-treated oocytes while the opposite profile was observed upon melatonin supplementation. In conclusion, to our knowledge, this is the first study reporting that melatonin can protect oocytes and embryos from NAM-induced injury through its ROS-scavenging activity together with potential interaction with NAM methylation signaling.

The ability of two nearly-touching plasmonic nanoparticles to squeeze light into a nanometer gap has provided a myriad of fundamental insights into light–matter interaction. In this work, we construct a nanoelectromechanical system (NEMS) that capitalizes on the unique, singular behavior that arises at sub-nanometer particle-spacings to create an electro-optical modulator. Using in situ electron energy loss spectroscopy in a transmission electron microscope, we map the spectral and spatial changes in the plasmonic modes as they hybridize and evolve from a weak to a strong coupling regime. In the strongly-coupled regime, we observe a very large mechanical tunability (~250 meV/nm) of the bonding-dipole plasmon resonance of the dimer at ~1 nm gap spacing, right before detrimental quantum effects set in. We leverage our findings to realize a prototype NEMS light-intensity modulator operating at ~10 MHz and with a power consumption of only 4 fJ/bit., Squeezing light into a nanometer gap offers strong light–matter interaction. Here, the authors develop a nanoelectromechanical system to dynamically control the gap of a plasmonic dimer at nanometer scale, enabling the realization of a light-intensity modulator that operates at high speed and with a low power consumption.

The effect of early coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation (STE) is still controversial. It is not known which subgroups of patients without STE are the most likely to benefit. The objective of this study was to evaluate the association between emergency CAG and neurologic outcomes and identify subgroups with improved outcomes when emergency CAG was performed. This prospective, multicenter, observational cohort study was based on data from the Korean Hypothermia Network prospective registry (KORHN-PRO) 1.0. Adult OHCA patients who were treated with targeted temperature management (TTM) without any obvious extracardiac cause were included. Patients were dichotomized into early CAG (&le, 24 h) and no early CAG (&gt, 24 h or not performed) groups. High-risk patients were defined as having the Global Registry of Acute Coronary Events (GRACE) score &gt, 140, time from collapse to return of spontaneous circulation (ROSC) &gt, 30 min, lactate level &gt, 7.0 mmol/L, arterial pH &lt, 7.2, cardiac enzyme elevation and ST deviation. The primary outcome was good neurologic outcome at 6 months after OHCA. Of the 1373 patients from the KORHN-PRO 1.0 database, 678 patients met the inclusion criteria. The early CAG group showed better neurologic outcomes at 6 months after cardiac arrest (CA) (adjusted odds ratio: 2.21 (1.27&ndash, 3.87), p = 0.005). This was maintained even after propensity score matching (adjusted odds ratio: 2.23 (1.39&ndash, 3.58), p &lt, 0.001). In the subgroup analysis, high-risk patients showed a greater benefit from early CAG. In contrast, no significant association was found in low-risk patients. Early CAG was associated with good neurologic outcome at 6 months after CA and should be considered in high-risk patients.

Graphical abstract, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents.

Direct laser writing (DLW) has been shown to render 3D polymeric optical components, including lenses, beam expanders, and mirrors, with submicrometer precision. However, these printed structures are limited to the refractive index and dispersive properties of the photopolymer. Here, we present the subsurface controllable refractive index via beam exposure (SCRIBE) method, a lithographic approach that enables the tuning of the refractive index over a range of greater than 0.3 by performing DLW inside photoresist-filled nanoporous silicon and silica scaffolds. Adjusting the laser exposure during printing enables 3D submicron control of the polymer infilling and thus the refractive index and chromatic dispersion. Combining SCRIBE’s unprecedented index range and 3D writing accuracy has realized the world’s smallest (15 µm diameter) spherical Luneburg lens operating at visible wavelengths. SCRIBE’s ability to tune the chromatic dispersion alongside the refractive index was leveraged to render achromatic doublets in a single printing step, eliminating the need for multiple photoresins and writing sequences. SCRIBE also has the potential to form multicomponent optics by cascading optical elements within a scaffold. As a demonstration, stacked focusing structures that generate photonic nanojets were fabricated inside porous silicon. Finally, an all-pass ring resonator was coupled to a subsurface 3D waveguide. The measured quality factor of 4600 at 1550 nm suggests the possibility of compact photonic systems with optical interconnects that traverse multiple planes. SCRIBE is uniquely suited for constructing such photonic integrated circuits due to its ability to integrate multiple optical components, including lenses and waveguides, without additional printed supports., 3D printing: SCRIBE tunes refractive index within optical elements A 3D printing technique can make a tiny structure with a varying refractive index, opening the door for manufacturing lenses and waveguides with interesting properties. Subsurface controllable refractive index via beam exposure (SCRIBE), developed by Paul V. Braun and colleagues at the University of Illinois at Urbana Champaign, involves changing a laser’s power to variably fill the nanosized pores of a silicon scaffold with photosensitive polymer. This tunes the refractive index within the final, fabricated, submicron-scale structure, causing visible light to bend differently within it according to where it passes. SCRIBE was used to fabricate a 15-micrometer diameter, spherical Luneburg lens in which the refractive index decreases from its core towards the surface. SCRIBE is particularly suited for constructing multiple components, like lenses and waveguides, for photonic integrated circuits, without the need for additionally printed supports.

Highlights • Lycorine inhibited MERS-CoV, SARS-CoV, and SARS-CoV-2 infections. • Lycorine directly inhibited MERS-CoV RdRp activity. • Lycorine interacts with SARS-CoV-2 RdRp through hydrogen bonding. • Lycorine is a non-nucleoside direct-acting antiviral against emerging coronavirus., Graphical abstract Image, graphical abstract, Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function. Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections. Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp. Results: Lycorine efficiently inhibited these CoVs with IC50 values of 2.123±0.053, 1.021±0.025, and 0.878±0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC50 of 1.406 ± 0.260 μM, compared with remdesivir's IC50 value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (−6.2 kcal/mol) were higher than those of remdesivir (−4.7 kcal/mol). Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

Dielectric microcavities with quality factors (Q-factors) in the thousands to billions markedly enhance light–matter interactions, with applications spanning high-efficiency on-chip lasing, frequency comb generation and modulation and sensitive molecular detection. However, as the dimensions of dielectric cavities are reduced to subwavelength scales, their resonant modes begin to scatter light into many spatial channels. Such enhanced scattering is a powerful tool for light manipulation, but also leads to high radiative loss rates and commensurately low Q-factors, generally of order ten. Here, we describe and experimentally demonstrate a strategy for the generation of high Q-factor resonances in subwavelength-thick phase gradient metasurfaces. By including subtle structural perturbations in individual metasurface elements, resonances are created that weakly couple free-space light into otherwise bound and spatially localized modes. Our metasurface can achieve Q-factors >2,500 while beam steering light to particular directions. High-Q beam splitters are also demonstrated. With high-Q metasurfaces, the optical transfer function, near-field intensity and resonant line shape can all be rationally designed, providing a foundation for efficient, free-space-reconfigurable and nonlinear nanophotonics.

The PPARs (peroxisome proliferator-activated receptors) play critical roles in the regulation of lipid and glucose metabolism. PPAR&delta, a member of the PPARs family, is associated with decreased susceptibility to ectopic lipid deposition and is implicated in the regulation of mitochondrial processes. The current study aimed to determine the role of PPAR&delta, in fatty acid &beta, oxidation and its influence on PEPCK for the lipogenic/lipolytic balance during in vitro bovine oocyte maturation and embryo development. Activation of PPAR&delta, by GW501516, but not 2-BP, was indicated by intact embryonic PEPCK (cytosolic) and CPT1 expression and the balance between free fatty acids and mitochondrial &beta, oxidation that reduced ROS and inhibited p-NF-&kappa, B nuclear localization. Genes involved in lipolysis, fatty acid oxidation, and apoptosis showed significant differences after the GW501516 treatment relative to the control- and 2-BP-treated embryos. GSK3787 reversed the PPAR&delta, induced effects by reducing PEPCK and CPT1 expression and the mitochondrial membrane potential, revealing the importance of PPAR&delta, /PEPCK and PPAR&delta, /CPT1 for controlling lipolysis during embryo development. In conclusion, GW501516-activated PPAR&delta, maintained the correlation between lipolysis and lipogenesis by enhancing PEPCK and CPT1 to improve bovine embryo quality.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a very rare disease entity, especially in the esophagus. The diagnosis of GNET is based on histologic, immunohistochemical, and genetic findings. The choice of treatment is complete resection, and further treatment options can be considered. Herein, we describe a case of successful surgical treatment of a 23-year-old man with recurrent malignant esophageal GNET.

Voltage-controlled magnetic anisotropy (VCMA) has attracted great attention as it allows faster switching and lower energy consumption compared to traditional spin-transfer torque-based magnetization switching. In this paper, we evaluate the operating margin and switching probability of VCMA-based magnetic tunnel junctions using realistic material and device parameters. For this paper, we developed a physics-based SPICE model that incorporates various VCMA parameters such as VCMA coefficient, energy barrier, time constant, and external magnetic field. Switching probability of a VCMA device was obtained by running Monte Carlo simulations including thermal fluctuation effects. A design space exploration was performed using the proposed simulation framework. The highest switching probabilities we were able to achieve were 94.9%, 84.8%, and 53.5%, for VCMA coefficient values of 33, 105, and $290\,\,\text {fJ}\cdot \text {V}^{-1}\cdot \text {m}^{-1}$ , respectively. Our study shows that for VCMA devices to become viable, their switching probability must be improved significantly either through new physics or material innovation.

The medial and lateral plantar nerves are branched from the tibial nerve and move to the tip of the toes. A variation of medial plantar nerve was found on the left side of a 78-year-old Korean male cadaver. The tibial nerve was divided into the lateral and medial plantar nerves beneath the plantar flexor. The medial plantar nerve passed deep to plantar aponeurosis and superficial to the flexor digitorum brevis. It gave off a common plantar digital nerve and then divided into three proper plantar digital nerves near the metatarsal bases. In this article, we report a superficial course of the medial plantar nerve and describe its unique morphology and discuss the clinical significance of this variation.