The molecular epidemiology and clinical implication of methicillin-resistant Staphylococcus aureus (MRSA) sequence types in pediatric bacteremia: a restrospective observational study, 2016-2021.

BACKGROUND: While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. METHODS: Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. RESULTS: The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). CONCLUSION: The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.

Characterization of Ceftriaxone-Resistant Haemophilus influenzae Among Korean Children.

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.

Enhancing biosynthesis of 2'-Fucosyllactose in Escherichia coli through engineering lactose operon for lactose transport and α -1,2-Fucosyltransferase for solubility.

2'-Fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and one of the most actively studied human milk oligosaccharides (HMOs). When 2'-FL is produced through biological production using a microorganism, like Escherichia coli, d-lactose is often externally fed as an acceptor substrate for fucosyltransferase (FT). When d-glucose is used as a carbon source for the cell growth and d-lactose is transported by lactose permease (LacY) in lac operon, d-lactose transport is under the control of catabolite repression (CR), limiting the supply of d-lactose for FT reaction in the cell, hence decreasing the production of 2'-FL. In this study, a remarkable increase of 2'-FL production was achieved by relieving the CR from the lac operon of the host E. coli BL21 and introducing adequate site-specific mutations into α-1,2-FT (FutC) for enhancement of catalytic activity and solubility. For the host engineering, the native lac promoter (Plac ) was substituted for tac promoter (Ptac ), so that the lac operon could be turned on, but not subjected to CR by high d-glucose concentration. Next, for protein engineering of FutC, family multiple sequence analysis for conserved amino acid sequences and protein-ligand substrate docking analysis led us to find several mutation sites, which could increase the solubility of FutC and its activity. As a result, a combination of four mutation sites (F40S/Q150H/C151R/Q239S) was identified as the best candidate, and the quadruple mutant of FutC enhanced 2'-FL titer by 2.4-fold. When the above-mentioned E. coli mutant host transformed with the quadruple mutant of futC was subjected to fed-batch culture, 40 g l-1 of 2'-FL titer was achieved with the productivity of 0.55 g l-1 h-1 and the specific 2'-FL yield of 1.0 g g-1 dry cell weight.

Probing twisted intramolecular charge transfer of pyrene derivatives as organic emitters in OLEDs.

Intramolecular charge transfer (ICT) plays a critical role in determining the photophysical properties of organic molecules, including their luminescence efficiencies. Twisted intramolecular charge transfer (TICT) is a process in which structural change accompanies ICT. Herein, we used time-resolved spectroscopy to study TICT in pyrene derivatives that are promising blue organic light emitting diode (OLED) emitter candidates; these derivatives show strong solvent-dependent charge-transfer (CT) behavior with unique fluorescence properties, increased fluorescence intensity in polar solvent. Slight structural changes that do not affect excited state dynamics were observed in nonpolar solvents, while polar solvents were found to affect excited state dynamics and CT characteristics, which affect their unusual fluorescence behavior. The TICT behavior of these pyrene derivatives can be modulated through structural modification. Our study provides valuable guidelines for the control of optical properties, including the luminescence efficiencies of OLED emitters that show TICT characteristics.

Classification of the Sidewalk Condition Using Self-Supervised Transfer Learning for Wheelchair Safety Driving.

The demand for wheelchairs has increased recently as the population of the elderly and patients with disorders increases. However, society still pays less attention to infrastructure that can threaten the wheelchair user, such as sidewalks with cracks/potholes. Although various studies have been proposed to recognize such challenges, they mainly depend on RGB images or IMU sensors, which are sensitive to outdoor conditions such as low illumination, bad weather, and unavoidable vibrations, resulting in unsatisfactory and unstable performance. In this paper, we introduce a novel system based on various convolutional neural networks (CNNs) to automatically classify the condition of sidewalks using images captured with depth and infrared modalities. Moreover, we compare the performance of training CNNs from scratch and the transfer learning approach, where the weights learned from the natural image domain (e.g., ImageNet) are fine-tuned to the depth and infrared image domain. In particular, we propose applying the ResNet-152 model pre-trained with self-supervised learning during transfer learning to leverage better image representations. Performance evaluation on the classification of the sidewalk condition was conducted with 100% and 10% of training data. The experimental results validate the effectiveness and feasibility of the proposed approach and bring future research directions.

Increasing the Energy Gap between Band-Edge and Trap States Slows Down Picosecond Carrier Trapping in Highly Luminescent InP/ZnSe/ZnS Quantum Dots.

Non-toxic InP-based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, compared to Cd-based quantum dots (QDs), for better device efficiency and long-term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state-of-the-art InP-based QD with near-unity luminescence. Here, it is shown that using time-resolved spectroscopic measurements of systematically size-controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band-edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band-edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP-based QDs.

Hidden Charge Order in an Iron Oxide Square-Lattice Compound.

Since the discovery of charge disproportionation in the FeO_{2} square-lattice compound Sr_{3}Fe_{2}O_{7} by Mössbauer spectroscopy more than fifty years ago, the spatial ordering pattern of the disproportionated charges has remained "hidden" to conventional diffraction probes, despite numerous x-ray and neutron scattering studies. We have used neutron Larmor diffraction and Fe K-edge resonant x-ray scattering to demonstrate checkerboard charge order in the FeO_{2} planes that vanishes at a sharp second-order phase transition upon heating above 332 K. Stacking disorder of the checkerboard pattern due to frustrated interlayer interactions broadens the corresponding superstructure reflections and greatly reduces their amplitude, thus explaining the difficulty of detecting them by conventional probes. We discuss the implications of these findings for research on "hidden order" in other materials.

OH molecule-involved formation of point defects in monolayer graphene.

Point defects in freestanding graphene monolayers such as monovacancies (MVs) and divacancies have been investigated at atomic scale with aberration-corrected transmission electron microscopy and theoretical calculations. In general, these defects can be formed simply by the absence of individual carbon atoms and carbon bond reconstructions in the graphene lattice under electron and ion irradiation. However, in this study, we found that oxygen and hydrogen atoms can be involved in the formation of these point defects caused by the simultaneous detachment of oxygen-carbon atoms. Here we report the effect of the oxygen and hydrogen atoms on the graphene surface forming the point defects under electron beam irradiation, and their role of stabilizing other MVs when composed of 13-5 ring pairs. In addition, theoretical analysis using density functional theory calculations demonstrates that the participating atoms can form the point defects in the intermediate states and stabilize 13-5 ring pairs under electron beam irradiation.

Gaze in the Dark: Gaze Estimation in a Low-Light Environment with Generative Adversarial Networks.

In smart interactive environments, such as digital museums or digital exhibition halls, it is important to accurately understand the user's intent to ensure successful and natural interaction with the exhibition. In the context of predicting user intent, gaze estimation technology has been considered one of the most effective indicators among recently developed interaction techniques (e.g., face orientation estimation, body tracking, and gesture recognition). Previous gaze estimation techniques, however, are known to be effective only in a controlled lab environment under normal lighting conditions. In this study, we propose a novel deep learning-based approach to achieve a successful gaze estimation under various low-light conditions, which is anticipated to be more practical for smart interaction scenarios. The proposed approach utilizes a generative adversarial network (GAN) to enhance users' eye images captured under low-light conditions, thereby restoring missing information for gaze estimation. Afterward, the GAN-recovered images are fed into the convolutional neural network architecture as input data to estimate the direction of the user gaze. Our experimental results on the modified MPIIGaze dataset demonstrate that the proposed approach achieves an average performance improvement of 4.53%-8.9% under low and dark light conditions, which is a promising step toward further research.

Double-Spiral Hexagonal Boron Nitride and Shear Strained Coalescence Boundary.

Among the different growth mechanisms for two-dimensional (2D) hexagonal boron nitride (h-BN) synthesized using chemical vapor deposition, spiraling growth of h-BN has not been reported. Here we report the formation of intertwined double-spiral few-layer h-BN that is driven by screw dislocations located at the antiphase boundaries of monolayer domains. The microstructure and stacking configurations were studied using a combination of dark-field and atomic resolution transmission electron microscopy. Distinct from other 2D materials with single-spiral structures, the double-spiral structure enables the intertwined h-BN layers to preserve the most stable AA' stacking configuration. We also found that the occurrence of shear strains at the boundaries of merged spiral islands is dependent on the propagation directions of encountering screw dislocations and presented the strained features by density functional theory calculations and atomic image simulations. This study unveils the double-spiral growth of 2D h-BN multilayers and the creation of a shear strain band at the coalescence boundary of two h-BN spiral clusters.

BAP1 functions as a tumor promoter in prostate cancer cells through EMT regulation.

BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that has long been considered to be a tumor suppressor in various tumors, including renal cell carcinoma, uveal melanoma, mesothelioma, and cutaneous melanoma. However, the involvement of BAP1 in the progression of prostate cancer has not been studied until recently. Herein, we investigated the tumor promoting function of BAP1 in the context of prostate cancer. Analysis of The Cancer Genome Atlas (TCGA) data set showed that prostate cancer patients express high levels of BAP1 mRNA. High BAP1 expression is inversely correlated with disease-free survival in patients with prostate cancer. Among the prostate cell lines tested, BAP1 expression was high in tumorigenic and metastatic cell lines, but was low in normal prostate cell line. Knockdown of BAP1 in PC3 or DU145 cells induced mesenchymal-to-epithelial transition (MET). Further, BAP1-knockdown resulted in decreased migration and invasion of PC3 and DU145 cells. Conversely, overexpression of BAP1 in RWPE1, a normal prostate cell line, induced the migratory and invasive properties. Collectively, our findings identified that BAP1 has a tumor promoting function in prostate cancer cells, and suggest that BAP1 can serve as a potential therapeutic target for prostate cancer.

USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells.

Regulation of target proteins by the ubiquitin-proteasome system (UPS) is common in a wide range of cellular events, including transcriptional regulation, cell cycle progression, differentiation, and tumorigenesis. Ubiquitin-specific protease 7 (USP7) has been implicated in tumor development and metastasis in various malignancies through the regulation of target protein stability. In this study, we found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. In prostate cancer cells, the transcriptional repression function of EZH2 was inhibited by USP7-knockdown. Furthermore, ectopic introduction of EZH2 restored the cell migration, invasion, and sphere-forming potential of prostate cancer cells, which had been decreased by USP7-knockdown. Moreover, combined treatment with the USP7-specific inhibitor P5091 and EZH2 inhibitors, such as GSK126, EPZ6438, and DZNep, induced synergistic inhibitory effects on cell migration, invasion, and sphere-forming potential in prostate cancer cells. Collectively, our findings revealed that the promotion of the malignancy-associated characteristics of prostate cancer cells by USP7 was in part due to EZH2 stabilization. Thus, we suggest that simultaneous treatment with a USP7 inhibitor and an EZH2 inhibitor could be a rational strategy for treating EZH2-dependent cancers.

Green-light-selective organic photodiodes for full-color imaging.

In this work, organic photodiodes (OPDs) based on two newly synthesized p-type dipolar small molecules are reported for application to green-light-selective OPDs. In order to reduce the blue-color absorption induced by the use of C60 as the n-type material in a bulk heterojunction (BHJ), the electron donor:electron acceptor composition ratio is tuned in the BHJ. With this light manipulation approach, the blue-wavelength external quantum efficiency (EQE) is minimized to 18% after reducing the C60 concentration in the center part of the BHJ. The two p-type molecules get a cyanine-like character with intense and sharp absorption in the green color by adjusting the strength of their donating and accepting parts and by choosing a selenophene unit as a π-linker. When combined to C60, the green-wavelength EQE reaches 70% in a complete device composed of two transparent electrodes. Finally, the optical simulation shows the good color-balance performance of hybrid full-color image sensor without an additional filter by using the developed green OPD as the top-layer in stacked device architecture.

Efficacy of forced-air warming and warmed intravenous fluid for prevention of hypothermia and shivering during caesarean delivery under spinal anaesthesia: A randomised controlled trial.

BACKGROUND: Peri-operative hypothermia and shivering are frequent events in patients during caesarean delivery under spinal anaesthesia. OBJECTIVE: We assessed the efficacy of combined pre-anaesthetic forced-air warming in combination with warmed intravenous fluid infusion for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. DESIGN: A randomised controlled study. SETTING: A tertiary care teaching hospital from July 2017 to April 2018. PATIENTS: A total of 50 pregnant women, American Society of Anaesthesiologists physical status 2, aged 20 to 45 years, scheduled for caesarean delivery under spinal anaesthesia. INTERVENTION: Patients were enrolled and randomised into two groups: an active warming group (n = 25), which received combined pre-anaesthetic whole body forced-air warming for 15 min and prewarmed intravenous fluids, and a control group, which received no active warming or warmed fluids (C group; n = 25). Spinal anaesthesia was induced with 10 mg bupivacaine containing fentanyl (10 µg). MAIN OUTCOME MEASURES: Tympanic membrane temperature and shivering severity were measured at baseline and every 10 min during surgery, and then every 10 min for 1 h postoperatively. Neonatal outcomes (tympanic membrane temperature at birth, umbilical venous blood pH, Apgar score) were also recorded. RESULTS: The incidences of peri-operative hypothermia (0 vs. 48%, P < 0.001) and shivering (22 vs. 52%, P = 0.031) were significantly lower in the active warming than in the C group. The maximum temperature change was also significantly lower in the active warming than in the C group. Maternal thermal comfort scores were higher in the active warming than in the C group. Neonatal parameters were not significantly different between the groups. CONCLUSION: The combination of pre-anaesthetic forced-air warming and warmed intravenous fluid infusions appears to be effective for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. TRIAL REGISTRATION: This trial was registered with Clinical Trials.gov (identifier: NCT03256786).

Direct observation of leakage currents in a metal-insulator-metal capacitor using in situ transmission electron microscopy.

With the acceleration of the scaling down of integrated circuits, it has become very challenging to fabricate a metal-insulator-metal (MIM) capacitor with a high capacitance density and low leakage current for nanoscale dynamic random access memory. Yttria-stabilized-zirconia (YSZ) thin films, one of the insulators in the constitution of MIM capacitors, have been reported to have various crystal structures from the monoclinic phase to the cubic phase according to different Y doping levels. The electrical characteristics depend on the crystal structure of the YSZ thin film. Here, we report the local crystallization of YSZ thin films via Joule heating and the leakage current induced during in situ transmission electron microscopy biasing tests. We studied the crystallization process and the increase in the leakage current using experimental and simulation results. It is important to understand the relationship between the crystallinity and electrical properties of YSZ thin films in MIM capacitors.

RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer.

Wnt family members play diverse roles in development and disease. Noncanonical Wnt ligands can inhibit canonical Wnt signaling depending on the cellular context; however, the underlying mechanism of this antagonism remains poorly understood. Here we identify a specific mechanism of orphan nuclear receptor RORalpha-mediated inhibition of canonical Wnt signaling in colon cancer. Wnt5a/PKCalpha-dependent phosphorylation on serine residue 35 of RORalpha is crucial to link RORalpha to Wnt/beta-catenin signaling, which exerts inhibitory function of the expression of Wnt/beta-catenin target genes. Intriguingly, there is a significant correlation of reduction of RORalpha phosphorylation in colorectal tumor cases compared to their normal counterpart, providing the clinical relevance of the findings. Our data provide evidence for a role of RORalpha, functioning at the crossroads between the canonical and the noncanonical Wnt signaling pathways, in mediating transrepression of the Wnt/beta-catenin target genes, thereby providing new approaches for the development of therapeutic agents for human cancers.

Negative regulation of hypoxic responses via induced Reptin methylation.

Lysine methylation within histones is crucial for transcriptional regulation and thus links chromatin states to biological outcomes. Although recent studies have extended lysine methylation to nonhistone proteins, underlying molecular mechanisms such as the upstream signaling cascade that induces lysine methylation and downstream target genes modulated by this modification have not been elucidated. Here, we show that Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. Methylated Reptin binds to the promoters of a subset of hypoxia-responsive genes and negatively regulates transcription of these genes to modulate cellular responses to hypoxia.

Effect of pre-warming on perioperative hypothermia during holmium laser enucleation of the prostate under spinal anesthesia: a prospective randomized controlled trial.

BACKGROUND: The purpose of this study is to assess whether the application of preoperative forced air warming set to high temperature (> 43 °C) for brief period can increase temperature on admission to the postanesthesia care unit (PACU) and prevent hypothermia or shivering during holmium laser enucleation of the prostate performed under spinal anesthesia. METHODS: Fifty patients were enrolled were assigned randomly to receive passive insulation (control group, n = 25) or forced-air skin surface warming for 20 min before spinal anesthesia (pre-warming group, n = 25). The primary outcome was temperature at PACU admission. RESULTS: The pre-warming group had a significantly higher temperature on admission to the PACU than the control group (35.9 °C [0.1] vs 35.6 °C [0.1], P = 0.023; 95% confidence interval of mean difference, 0.1 °C-0.5 °C). The trend of decreasing core temperature intraoperatively was not different between groups (P = 0.237), but intraoperative core temperature remained approximately 0.2 °C higher in the pre-warming group (P = 0.005). The incidence of hypothermia on admission to the PACU was significantly lower in the pre-warming group (56% vs 88%, P = 0.025). Shivering occurred in 14 patients in the control group, and 4 patients in the pre-warming group (P = 0.007). CONCLUSION: Brief pre-warming at 45 °C increased perioperative temperature and decreased the incidence of hypothermia and shivering. However, it was not sufficient to modify the decline of intraoperative core temperature or completely prevent hypothermia and shivering. Continuing pre-warming to immediately before induction of spinal anesthesia or combining pre-warming with intraoperative active warming may be necessary to produce clearer thermal benefits in this surgical population. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov, NCT03184506 , 5th June 2017.

Atomic Scale Study on Growth and Heteroepitaxy of ZnO Monolayer on Graphene.

Atomically thin semiconducting oxide on graphene carries a unique combination of wide band gap, high charge carrier mobility, and optical transparency, which can be widely applied for optoelectronics. However, study on the epitaxial formation and properties of oxide monolayer on graphene remains unexplored due to hydrophobic graphene surface and limits of conventional bulk deposition technique. Here, we report atomic scale study of heteroepitaxial growth and relationship of a single-atom-thick ZnO layer on graphene using atomic layer deposition. We demonstrate atom-by-atom growth of zinc and oxygen at the preferential zigzag edge of a ZnO monolayer on graphene through in situ observation. We experimentally determine that the thinnest ZnO monolayer has a wide band gap (up to 4.0 eV), due to quantum confinement and graphene-like structure, and high optical transparency. This study can lead to a new class of atomically thin two-dimensional heterostructures of semiconducting oxides formed by highly controlled epitaxial growth.