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Abstract In this work, we study the end-of-the-world (EOW) branes anchored to the boundaries of BCFT $${}_2$$ 2 dual to the BTZ black hole. First, we explore the thermodynamics of the boundary system consisting of the conformal boundary and two EOW branes. This thermodynamics is extended by the tension appearing as the effective cosmological constant of JT black holes on the EOW branes. The tension contribution is identified with the shadow entropy equivalent to the boundary entropy of the BCFT $${}_2$$ 2 . The thermodynamics of the JT black holes and the bulk of BCFT $${}_2$$ 2 can be combined into a novel grafted thermodynamics based on the first law. Second, we focus on the observer’s view of the EOW branes by lowering the temperature. We show that the EOW branes generate a scale called “reefs” inside the horizon. This scale also appears in the grafted thermodynamics. At high temperatures, observers on the EOW branes see their respective event horizons. The reef starts to grow relatively to the horizon size at the temperature, $$T_{grow}$$ T grow . As the temperature cools down the reef area fills the entire interior of the JT black holes at the temperature $$T_{out}$$ T out . Then, the observers recognize their horizons disappear and see the large density of the energy flux. At this temperature, the two JT regions become causally connected. This connected spacetime has two asymptotic $$AdS_2$$ A d S 2 boundaries with a conformal matter. Also, we comment on the grafted thermodynamics to higher dimensions in Appendix B.

The extensive use of β-lactam antibiotics has led to significant resistance, primarily due to hydrolysis by β-lactamases. OXA class D β-lactamases can hydrolyze a wide range of β-lactam antibiotics, rendering many treatments ineffective. We investigated the effects of single amino acid substitutions in OXA-10 on its substrate spectrum. Broad-spectrum variants with point mutations were searched and biochemically verified. Three key residues, G157D, A124T, and N73S, were confirmed in the variants, and their crystal structures were determined. Based on an enzyme kinetics study, the hydrolytic activity against broad-spectrum cephalosporins, particularly ceftazidime, was significantly enhanced by the G157D mutation in loop 2. The A124T or N73S mutation close to loop 2 also resulted in higher ceftazidime activity. All structures of variants with point mutations in loop 2 or nearby exhibited increased loop 2 flexibility, which facilitated the binding of ceftazidime. These results highlight the effect of a single amino acid substitution in OXA-10 on broad-spectrum drug resistance. Structure–activity relationship studies will help us understand the drug resistance spectrum of β-lactamases, enhance the effectiveness of existing β-lactam antibiotics, and develop new drugs.

AbstractThe urgent demand for effective countermeasures against metallo-β-lactamases (MBLs) necessitates development of novel metallo-β-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Purpose We aimed to analyze the clinical characteristics, recurrence, neurological outcomes, and the impact of coronavirus disease 2019 pandemic in children who visited 2 emergency departments (EDs) with febrile seizure (FS). Methods We retrospectively reviewed medical records of 3,172 episodes, involving 2,510 children aged 6-60 months whose diagnoses were FSs at the EDs in 2 hospitals from 2013 through 2022. Through the review, we analyzed clinical characteristics and associated factors for the recurrence of FS. As a sub-analysis, the variables were compared between before (2017-2019) and during (2020-2022) the pandemic. Results A total of 3,172 FS-related visits to the EDs were found in 2,510 children. Of these, 890 children (35.5%) underwent recurrences of FS. The recurrence of FS was associated with boys (63.3% vs. 57.8%; P = 0.007), seizures lasting longer than 5 minutes (16.6% vs. 12.7%; P = 0.007), family history of FS (23.7% vs. 16.2%; P < 0.001), complex FS (13.3% vs. 8.0%; P < 0.001), and epilepsy diagnosed thereafter (9.1% vs. 3.0%; P < 0.001). During the pandemic, we noted a decrease in the number of FS-related visits to the EDs (from 1,274 to 383), an increase in the percentage of complex FS (9.3% vs. 13.8%; P = 0.012), and a decrease in the percentage of recurrent FS (49.4% vs. 33.4%; P < 0.001), compared to before the pandemic. Conclusion Our study identified factors associated with recurrence of FS, and confirmed the increase in complex FS with the decrease in the recurrence during the coronavirus disease 2019 pandemic. These findings could be helpful when caring for children with FS in EDs.

Background Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short‐term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. Methods and Results A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no‐flow and low‐flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. Conclusions Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.

A unified diagnostic criterion has yet to be established for sarcopenia. Therefore, we analyzed the reliability and validity of sarcopenia diagnosis using bioelectrical impedance analysis (BIA) compared with the gold standard, dual-energy X-ray absorptiometry (DEXA), and evaluated the predictive accuracy of BIA for diagnosis. The clinical trial, involving a total of 239 participants, was conducted between December 2018 and September 2019 on healthy volunteers without significant medical histories. The participants underwent health assessments, followed by sequential DEXA and BIA measurements. In both the low and normal appendicular skeletal muscle (ASM) groups, there were significant differences in the right arm, left arm, right leg, left leg, ASM, and ASM index (ASMI) between DEXA and BIA across all age groups (p < 0.05). BIA tended to overestimate compared to DEXA, but ASMI values for males and females were consistent with the criteria for sarcopenia. Bland–Altman analysis showed that each segment in both the low and normal ASM groups fell within the limits of agreement (LOA). The diagnosis of sarcopenia using BIA was significantly different from that using DEXA. However, it exhibited a significantly high correlation, fell within the LOA, and demonstrated high predictive accuracy. BIA can be considered an effective tool for diagnosing sarcopenia.

The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007–5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition.

Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.

The measurement of skeletal muscle mass is essential for the diagnosis of sarcopenia. Muscle ultrasonography has emerged as a useful tool for evaluating sarcopenia because it can be used to assess muscle quality and quantity. This study investigated whether muscle ultrasonography is effective for estimating appendicular skeletal muscle mass (ASM) and screening for sarcopenia. This study prospectively enrolled 212 healthy volunteers aged 40-80 years. ASM was measured using the bioelectrical impedance analysis. Muscle thickness (MT) and echo-intensity (EI) were measured in four muscles (biceps brachii, BB; triceps brachii, TB; rectus femoris, RF; biceps femoris, BF) on the dominant hand. A hold-out cross-validation method was used to develop and validate the ASM prediction equation. In the model development group, the ASM prediction equations were deduced as follows: estimated ASM for men (kg) = 0.167 × weight (kg) + 0.228 × height (cm) + 0.143 × MT of BF (mm)- 0.822 × EI to MT ratio of BB- 28.187 (R2 = 0.830) and estimated ASM for women (kg) = 0.115 × weight + 0.215 × height (cm) + 0.139 × MT of RF-0.638 × EI to MT ratio of BB- 23.502 (R2 = 0.859). In the cross-validation group, the estimated ASM did not significantly differ from the measured ASM in both men (p = 0.775; intraclass correlation coefficient [ICC] = 0.948) and women (p = 0.516; ICC = 0.973). In addition, multiple logistic regression analysis revealed that the ratios of EI to MT in the BF and RF muscles in men and MT in the BB muscle in women could be valuable parameters for sarcopenia screening. Therefore, our study suggests that muscle ultrasound could be an effective tool for estimating ASM and screening sarcopenia.

Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.

The aim of this study was to introduce the implemented MEDBIZ platform based on the internet of medical things (IoMT) supporting real-time digital health services for precision medicine. In addition, we demonstrated four empirical studies of the digital health ecosystem that could provide real-time healthcare services based on IoMT using real-world data from in-hospital and out-hospital patients. Implemented MEDBIZ platform based on the IoMT devices and big data to provide digital healthcare services to the enterprise and users. The big data platform is consisting of four main components: IoMT, core, analytics, and services. Among the implemented MEDBIZ platform, we performed four clinical trials that designed monitoring services related to chronic obstructive pulmonary disease, metabolic syndrome, arrhythmia, and diabetes mellitus. Of the four empirical studies on monitoring services, two had been completed and the rest were still in progress. In the metabolic syndrome monitoring service, two studies were reported. One was reported that intervention components, especially wearable devices and mobile apps, made systolic blood pressure, diastolic blood pressure, waist circumference, and glycosylated hemoglobin decrease after 6 months. Another one was presented that increasing high-density lipoprotein cholesterol and triglyceride levels were prevented in participants with the pre-metabolic syndrome. Also, self-care using healthcare devices might help prevent and manage metabolic syndrome. In the arrhythmia monitoring service, during the real-time monitoring of vital signs remotely at the monitoring center, 318 (15.9%) general hikers found abnormal signals, and 296 (93.1%) people were recommended for treatment. We demonstrated the implemented MEDBIZ platform based on IoMT supporting digital healthcare services by acquiring real-world data for getting real-world evidence. And then through this platform, we were developing software as a medical device, digital therapeutics, and digital healthcare services, and contributing to the development of the digital health ecosystem.

In this study, we investigated the gas-sensing mechanism in bottom-gate organic field-effect transistors (OFETs) using poly(triarylamine) (PTAA). A comparison of different device architectures revealed that the top-contact structure exhibited superior gas-sensing performance in terms of field-effect mobility and sensitivity. The thickness of the active layer played a critical role in enhancing these parameters in the top-contact structure. Moreover, the distance and pathway for charge carriers to reach the active channel were found to significantly influence the gas response. Additionally, the surface treatment of the SiO2 dielectric with hydrophobic self-assembled mono-layers led to further improvement in the performance of the OFETs and gas sensors by effectively passivating the silanol groups. Under optimal conditions, our PTAA-based gas sensors achieved an exceptionally high response (>200%/ppm) towards NO2. These findings highlight the importance of device and interface engineering for optimizing gas-sensing properties in amorphous polymer semiconductors, offering valuable insights for the design of advanced gas sensors.

BackgroundHyperkalemia monitoring is very important in patients with chronic kidney disease (CKD) in emergency medicine. Currently, blood testing is regarded as the standard way to diagnose hyperkalemia (ie, using serum potassium levels). Therefore, an alternative and noninvasive method is required for real-time monitoring of hyperkalemia in the emergency medicine department. ObjectiveThis study aimed to propose a novel method for noninvasive screening of hyperkalemia using a single-lead electrocardiogram (ECG) based on a deep learning model. MethodsFor this study, 2958 patients with hyperkalemia events from July 2009 to June 2019 were enrolled at 1 regional emergency center, of which 1790 were diagnosed with chronic renal failure before hyperkalemic events. Patients who did not have biochemical electrolyte tests corresponding to the original 12-lead ECG signal were excluded. We used data from 855 patients (555 patients with CKD, and 300 patients without CKD). The 12-lead ECG signal was collected at the time of the hyperkalemic event, prior to the event, and after the event for each patient. All 12-lead ECG signals were matched with an electrolyte test within 2 hours of each ECG to form a data set. We then analyzed the ECG signals with a duration of 2 seconds and a segment composed of 1400 samples. The data set was randomly divided into the training set, validation set, and test set according to the ratio of 6:2:2 percent. The proposed noninvasive screening tool used a deep learning model that can express the complex and cyclic rhythm of cardiac activity. The deep learning model consists of convolutional and pooling layers for noninvasive screening of the serum potassium level from an ECG signal. To extract an optimal single-lead ECG, we evaluated the performances of the proposed deep learning model for each lead including lead I, II, and V1-V6. ResultsThe proposed noninvasive screening tool using a single-lead ECG shows high performances with F1 scores of 100%, 96%, and 95% for the training set, validation set, and test set, respectively. The lead II signal was shown to have the highest performance among the ECG leads. ConclusionsWe developed a novel method for noninvasive screening of hyperkalemia using a single-lead ECG signal, and it can be used as a helpful tool in emergency medicine.

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Abstract We holographically study the finite-size scaling effects on macroscopic and microscopic quantum correlations deformed by excitation and condensation. The excitation (condensation) increases (decreases) the entanglement entropy of the system. We also investigate the two-point correlation function of local operators by calculating the geodesic length connecting two local operators. As opposed to the entanglement entropy case, the excitation (condensation) decreases (increases) the two-point function. This is because the screening effect becomes strong in the background with the large entanglement entropy. We further show that the holographic renormalization leads to the qualitatively same two-point function as the one obtained from the geodesic length.

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Abstract We investigate the time-dependent entanglement entropy in the AdS space with a dS boundary which represents an expanding spacetime. On this time-dependent spacetime, we show that the Ryu–Takayanagi formula, which is usually valid in the static spacetime, provides a leading contribution to the time-dependent entanglement entropy. We also study the leading behavior of the entanglement entropy between the visible and invisible universes in an inflationary cosmology. The result shows that the quantum entanglement monotonically decreases with time and finally saturates a constant value inversely proportional to the square of the Hubble constant. Intriguingly, we find that even in the expanding universes, the time-dependent entanglement entropy still satisfies the area law determined by the physical distance.

Objective: We aimed to present our initial experience with robotic single-port surgery performed using the da Vinci® SP surgical system for benign gynecologic diseases. Materials and methods: This retrospective cohort study was performed at an academic tertiary care hospital From December 2018 to January 2019. Thirty-one women with benign gynecologic diseases underwent robotic single-port surgery performed using the da Vinci® SP surgical system. Results: During the study period, hysterectomy, myomectomy, adnexectomy, and sacrocolpopexy were performed in seven, twelve, five, and seven women, respectively. The mean age and body mass index of patients, respectively, were 47.7 ± 12.8 years and 22.7 ± 3.1 kg/m2. In terms of operative outcomes, the mean docking time, operating time, estimated blood loss, and hospitalization time were 2.2 ± 2.1 min, 126.3 ± 61.6 min, 93.9 ± 76.9 mL, and 4.6 ± 0.7 days. There was no laparoconversion or major complication. Conclusion: Robotic single-port laparoscopy using the da Vinci® SP surgical system might be a suitable alternative surgical technique for various benign gynecologic diseases. However, further studies are required to clarify the feasibility and safety of the application of this novel robot surgical system. Keywords: Gynecology, Laparoscopy, Robotic surgery, Single-port surgery

In this paper, we analyze the effects of textile weaving and finishing processes on the performance of textile-based wearable antennas. Several textile-based patch antennas operating at 2.4 GHz were designed and fabricated for evaluation. All of them had the same geometry comprising a 1-mm-thick felt substrate in the middle, and silver ink screen-printed polyester fabric as the ground and patch at the bottom and on top. However, polyester fabric, the bare textile material for the conductive ground and patch was subjected to different weaving and finishing (tentering, scouring, and calendering) processes. It was observed that the antenna resonant frequency, bandwidth, radiation efficiency, and peak gain were varied by these processes, although the antenna geometry and screen-printing method were identical to each other. The best antenna exhibits a peak gain of 5.2 dBi and a radiation efficiency of 42.4%, while the worst shows corresponding values of 4.17 dBi and 34.8%. This implies that the weaving and finishing processes considerably impact textile-based wearable antenna performances.

BackgroundResearch on whether wearable devices and app-based interventions can effectively prevent metabolic syndrome (MetS) by increasing physical activity (PA) among middle-aged people living in the rural areas of South Korea remains insufficient. ObjectiveThe aim of this study was to determine whether mobile and wearable device interventions can improve health indicators, including PA, in MetS risk groups in rural South Korea. MethodsIn this clinical trial, performed from December 2019 to June 2020, participants were asked to use a wearable device (GalaxyWatch Active1) alone (standard intervention) or the wearable device and mobile app (Yonsei Health Korea) (enhanced intervention). Clinical measures and International Physical Activity Questionnaire (IPAQ) scores were evaluated initially and after 6 months. The number of steps was monitored through the website. The primary outcome was the difference in PA and clinical measures between the enhanced intervention and standard intervention groups. The secondary outcome was the decrease in MetS factors related to the change in PA. ResultsA total of 267 participants were randomly selected, 221 of whom completed the 6-month study. Among the 221 participants, 113 were allocated to the enhanced intervention group and 108 were allocated to the standard intervention group. After 6 months, the body weight and BMI for the enhanced intervention group decreased by 0.6 (SD 1.87) and 0.21 (SD 0.76), respectively (P

Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems; however, no effective inhibitors are currently clinically available. MBLs are classified into three subclasses: B1, B2, and B3. Although the amino acid sequences of MBLs are varied, their overall scaffold is well conserved. In this study, we systematically studied the primary sequences and crystal structures of all subclasses of MBLs, especially the core scaffold, the zinc-coordinating residues in the active site, and the substrate-binding pocket. We presented the conserved structural features of MBLs in the same subclass and the characteristics of MBLs of each subclass. The catalytic zinc ions are bound with four loops from the two central β-sheets in the conserved αβ/βα sandwich fold of MBLs. The three external loops cover the zinc site(s) from the outside and simultaneously form a substrate-binding pocket. In the overall structure, B1 and B2 MBLs are more closely related to each other than they are to B3 MBLs. However, B1 and B3 MBLs have two zinc ions in the active site, while B2 MBLs have one. The substrate-binding pocket is different among all three subclasses, which is especially important for substrate specificity and drug resistance. Thus far, various classes of β-lactam antibiotics have been developed to have modified ring structures and substituted R groups. Currently available structures of β-lactam-bound MBLs show that the binding of β-lactams is well conserved according to the overall chemical structure in the substrate-binding pocket. Besides β-lactam substrates, B1 and cross-class MBL inhibitors also have distinguished differences in the chemical structure, which fit well to the substrate-binding pocket of MBLs within their inhibitory spectrum. The systematic structural comparison among B1, B2, and B3 MBLs provides in-depth insight into their substrate specificity, which will be useful for developing a clinical inhibitor targeting MBLs.

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To date, the current COVID-19 pandemic caused by SARS-CoV-2 has infected 99.2 million while killed 2.2 million people throughout the world and is still spreading widely. The unavailability of potential therapeutics against this virus urges to search and develop new drugs. SARS-CoV-2 enters human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptor expressed on human cell surface through utilizing receptor-binding domain (RBD) of its spike glycoprotein. The RBD is highly conserved and is also a potential target for blocking its interaction with human cell surface receptor. We designed short peptides on the basis of our previously reported truncated ACE2 (tACE2) for increasing the binding affinity as well as the binding interaction network with RBD. These peptides can selectively bind to RBD with much higher affinities than the cell surface receptor. Thus, these can block all the binding residues required for binding to cell surface receptor. We used selected amino acid regions (21–40 and 65–75) of ACE2 as scaffold for the de novo peptide design. Our designed peptide Pep1 showed interactions with RBD covering almost all of its binding residues with significantly higher binding affinity (−13.2 kcal mol−1) than the cell surface receptor. The molecular dynamics (MD) simulation results showed that designed peptides form a stabilized complex with RBD. We suggest that blocking the RBD through de novo designed peptides can serve as a potential candidate for COVID-19 treatment after further clinical investigations.

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Abstract We studied the holographic entanglement entropy for a strip and sharp wedge entangling regions in momentum relaxation systems. In the case of strips, we found analytic and numerical results for the entanglement entropy and examined the effect of the electric field on the entanglement entropy. We also studied the entanglement entropy of wedges and confirmed that there is a linear change due to the electric field. In this case, we showed that the entanglement entropy change is interestingly proportional to the thermoelectric conductivity which is a measurable quantity. Also, we discussed comparable calculations with ABJM theory and we suggested an experiment for our result.

ABSTRACTResistance to β-lactams is one of the most serious problems associated with Gram-negative infections. β-Lactamases are able to hydrolyze β-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-β-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.

Microstructural control during the solution processing of small-molecule semiconductors (namely, soluble acene) is important for enhancing the performance of field-effect transistors (FET) and sensors. This focused review introduces strategies to enhance the gas-sensing properties (sensitivity, recovery, selectivity, and stability) of soluble acene FET sensors by considering their sensing mechanism. Defects, such as grain boundaries and crystal edges, provide diffusion pathways for target gas molecules to reach the semiconductor-dielectric interface, thereby enhancing sensitivity and recovery. Representative studies on grain boundary engineering, patterning, and pore generation in the formation of soluble acene crystals are reviewed. The phase separation and microstructure of soluble acene/polymer blends for enhancing gas-sensing performance are also reviewed. Finally, flexible gas sensors using soluble acenes and soluble acene/polymer blends are introduced, and future research perspectives in this field are suggested.

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Hutchinson–Gilford progeria syndrome (HGPS) is a rare, fatal, and genetic disorder in the LMNA gene encoding for prelamin A. Normally, prelamin A is processed to become lamin A protein. In HGPS patients, there is a heterozygous mutation in LMNA gene, in which there is a deletion of genetic codes responsible for 50 amino acids at the C-terminus of prelamin A. The processing of the abnormal prelamin A results in abnormal lamin A protein, called progerin, causing symptoms of accelerated early aging, probably due to the inflammaging process. It is well known that adipose tissue-derived mesenchymal stem cells (MSCs) have anti-inflammatory effects by modulating inflammatory cytokines and by extracellular vesicles. Here, we present a case of an HGPS patient who responded positively to injections of allogeneic haploidentical adipose tissue-derived stromal vascular fractions containing MSCs by showing rapid height and weight growth along with increased blood level of insulin-like growth factor 1.

Abstract Background With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan. Methods This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n = 208), Cambodia (n = 60), and Uzbekistan (n = 161) who had access to the Internet and were living abroad for at least 6 months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine. Results We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions > 3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks. Conclusions Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

Abstract We holographically investigate the renormalization group flow in a two-dimensional conformal field theory deformed by a relevant operator. If the relevant operator allows another fixed point, the UV conformal field theory smoothly flows to a new IR conformal field theory. From the holographic point of view, such a renormalization group flow can be realized as a dual geometry interpolating two different AdS boundaries. On this interpolating geometry, we investigate how the c-function of the entanglement entropy behaves along the RG flow analytically and numerically, which reproduces the expected central charges of UV and IR. We also show that the c-function monotonically decreases from UV to IR without any phase transition.

Abstract Background Glycerol is a major byproduct of the biodiesel industry and can be converted to 1,3-propanediol (1,3-PDO) by microorganisms through a two-step enzymatic reaction. The production of 1,3-PDO from glycerol using microorganisms is accompanied by formation of unwanted byproducts, including lactate and 2,3-butanediol, resulting in a low-conversion yield. Results Klebsiella pneumoniae was metabolically engineered to produce high-molar yield of 1,3-PDO from glycerol. First, the pathway genes for byproduct formation were deleted in K. pneumoniae. Then, glycerol assimilation pathways were eliminated and mannitol was co-fed to the medium. Finally, transcriptional regulation of the dha operon were genetically modified for enhancing 1,3-propanediol production. The batch fermentation of the engineered strain with co-feeding of a small amount of mannitol yielded 0.76 mol 1,3-PDO from 1 mol glycerol. Conclusions Klebsiella pneumoniae is useful microorganism for producing 1,3-PDO from glycerol. Implemented engineering in this study successfully improved 1,3-PDO production yield, which is significantly higher than those reported in previous studies.

Background: To describe the surgical technique and our initial experience of single-port laparoscopic neosalpingostomy (SP-LN) for treatment of hydrosalpinx. Materials and methods: This prospective observational study was carried out at University teaching hospitals. Ten women underwent SP-LN for hydrosalpinx between November 2012 and December 2015. Results: The mean (range) age and body mass index were 29.3 (21–36) years and 22.2 (17.7–27.1) kg/m2, respectively. Six women had a history of previous abdominal surgery; laparoscopic unilateral salpingectomy for tubal pregnancy in two, laparoscopic appendectomy in three, and laparotomy appendectomy in one. Six women underwent unilateral SP-LN and nine women underwent bilateral SP-LN. The mean (range) operating time, hemoglobin change, return of bowel activity, and length of hospital stay were 91.5 (70–120) minutes, 0.7 (0.1–1.6) g/dL, 19.9 (7.1–25.4) hours, and 3.7 (3–4) days, respectively. There was no conversion to multiport laparoscopy or laparotomy. There were no surgical or wound complications in any patient. Conclusion: SP-LN might be a feasible and safe alternative in women with hydrosalpinx. However, further study is needed to confirm this preliminary result and to explore the obstetric outcomes following SP-LN.

This study aimed to analyze long-term performance of JPCP (jointed plain concrete pavement) according to changes in standard mix design using evaluation of concrete properties based on Korea HPMS (highway pavement management system) and Korea LTPP (long-term pavement performance) data accumulated for over 15 years. The concrete pavements built in the 2010s by the specification of a durability-based mix design adopted in 2010 were found to have better performance with much fewer surface distresses than the concrete pavements built before 2010 by the specification of a classical strength-based mix design. Also, in order to realize long-life concrete pavement, experimental construction was carried out for high-durability concrete mix design. The performance monitoring data for the construction site implied that the high-durability mix design can make it possible to lead a long-life concrete pavement.

The purpose of this study is to prove the concept of the performance monitoring system of container terminals. PoC (Proof of Concept) is a realization of a certain method or idea in order to demonstrate its feasibility. The port authorities, such as government or local authority, are continually checking the performance of the terminals they invested in and want to reflect it in the development policy. They also want to increase competitiveness by checking performance levels, such as port handling volume, calling ships, resource utilization, and congestion. PPI (Port performance indicators) are classified into four categories: output (production), productivity, utilization, and service. In this study, 15 monitoring indicators for each stage by dividing the process from the ship’s entry to departure are defined. Four indicators, such as ship waiting ratio at anchorage, berth occupancy, storage occupancy, and truck turnaround time, are selected as PoC of monitoring platform. In addition, a method of collecting, processing, and expressing data on these four indicators in real time is presented. There are three steps to create PPI on monitoring platform. The information required for PPI is to be collected from the Port-MIS (Management Information System) and TOS (Terminal Operating System) databases. Second, the collected data from external entities are stored into the database after verification and classification. Third, descriptive PPI, predictive PPI are generated based on the input data. This study provides a 4-tier framework from the conceptual platform with the key elements of data presentation, data process and data interface and middleware. As a result of the study, it is proved to select monitoring indicators, define external entities, define internal elements of the system, develop systems, and present indicator results. However, in the process of collecting data outside the system, we have found there is confidential data of individual terminals. To this end, it is important to establish a mutual cooperation system for data collection.

The increasing incidence of community- and hospital-acquired infections with multidrug-resistant (MDR) bacteria poses a critical threat to public health and the healthcare system. Although β-lactam antibiotics are effective against most bacterial infections, some bacteria are resistant to β-lactam antibiotics by producing β-lactamases. Among β-lactamases, metallo-β-lactamases (MBLs) are especially worrisome as only a few inhibitors have been developed against them. In MBLs, the metal ions play an important role as they coordinate a catalytic water molecule that hydrolyzes β-lactam rings. We determined the crystal structures of different variants of PNGM-1, an ancient MBL with additional tRNase Z activity. The variants were generated by site-directed mutagenesis targeting metal-coordinating residues. In PNGM-1, both zinc ions are coordinated by six coordination partners in an octahedral geometry, and the zinc-centered octahedrons share a common face. Structures of the PNGM-1 variants confirm that the substitution of a metal-coordinating residue causes the loss of metal binding and β-lactamase activity. Compared with PNGM-1, subclass B3 MBLs lack one metal-coordinating residue, leading to a shift in the metal-coordination geometry from an octahedral to tetrahedral geometry. Our results imply that a subtle change in the metal-binding site of MBLs can markedly change their metal-coordination geometry and catalytic activity.

Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity.

Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

Military conflict has been a major challenge in the detection and control of emerging infectious diseases such as malaria. It poses issues associated with enhancing emergence and transmission of infectious diseases by destroying infrastructure and collapsing healthcare systems. The Orakzai agency in Pakistan has witnessed a series of intense violence and destruction. Military conflicts and instability in Afghanistan have resulted in the migration of refugees into the area and possible introduction of many infectious disease epidemics. Due to the ongoing violence and Talibanization, it has been a challenge to conduct an epidemiological study.All patients were sampled within the transmission season. After a detailed clinical investigation of patients, data were recorded. Baseline venous blood samples were taken for microscopy and nested polymerase chain reaction (nPCR) analysis. Plasmodium species were detected using nested PCR (nPCR) and amplification of the small subunit ribosomal ribonucleic acid (ssrRNA) genes using the primer pairs. We report a clinical assessment of the epidemic situation of malaria caused by Plasmodium vivax (86.5%) and Plasmodium falciparum (11.79%) infections with analysis of complications in patients such as decompensated shock (41%), anemia (8.98%), hypoglycaemia (7.3%), multiple convulsions (6.7%), hyperpyrexia (6.17%), jaundice (5%), and hyperparasitaemia (4.49%).This overlooked distribution of P. vivax should be considered by malaria control strategy makers in the world and by the Government of Pakistan. In our study, children were the most susceptible population to malaria infection while they were the least expected to use satisfactory prevention strategies in such a war-torn deprived region. Local health authorities should initiate malaria awareness programs in schools and malaria-related education should be further promoted at the local level reaching out to both children and parents.

BackgroundThis article presents long-term outcomes after correcting secondary bilateral cleft lip nasal deformities using a refined reverse-U incision and V-Y plasty or in combination with a composite graft in order to elongate the short columella.MethodsA total of forty-six patients underwent surgery between September 1996 and December 2008. The age of the patients ranged from 3 to 19 years of age. A bilateral reverse-U incision and V-Y plasty were used in 24 patients. A composite graft from the helical root was combined with a bilateral reverse-U incision in the 22 patients who possessed a severely shortened columella. The follow-up period ranged between 2 and 10 years.ResultsA total of 32 patients out of 46 were evaluated postoperatively. The average columella length was significantly improved from an average of 3.7 mm preoperatively to 8.5 mm postoperatively. The average ratio of the columella height to the alar base width was 0.18 preoperatively and 0.29 postoperatively. The postoperative basal and lateral views revealed a better shape of the nostrils and columella. The elongated columella, combined with a composite graft, presented good maintenance of the corrected position with no growth disturbance. A composite graft showed color mismatching in several patients. Twenty-six patients demonstrated no alar-columella web deformity and satisfactory symmetry of the nostrils. Four patients experienced a drooping and overhanging of the corrected alar-columella web.ConclusionsA bilateral reverse-U incision with V-Y plasty or in combination with a composite graft was effective in correcting secondary bilateral cleft lip nasal deformity.

The synchondrosis between the sixth and seventh costal cartilage is usually used for the base frame in autogenous ear reconstruction. If the synchondrosis is loose, a variety of modifications can be devised. This report introduces new methods for these problems. In cases of incomplete synchondrosis, only the surface of the base block margin was smoothly tapered without carving for the removal of the conchal deepening. The secure fixation of the two segments (helix and antihelix) to the base block using fine wire sutures gave stability to the unstable basal frame. After confirming that all the segments were assembled in one stable piece, the remaining conchal deepening of the basal framework was removed, and the outer lower portion of the basal cartilage was trimmed along its whole length. A total of 10 consecutive patients with microtia, ranging from 8 to 13 years old, were treated from 2008 to 2009. The follow-up period was 6 months to 2 years. Despite incomplete synchondrosis, the stable frameworks were constructed using the authors' method and aesthetically acceptable results were achieved. The proposed method can provide an easy way to make a stable cartilage framework regardless of the variable conditions of synchondrosis.

PurposeMitochondrial dysfunction can present with various symptoms depending on the organ it has affected. This research tried to analyze the ophthalmologic symptoms and ophthalmologic examination (OE) results in patients with mitochondrial disease (MD).MethodsSeventy-four patients diagnosed with mitochondrial respiratory chain complex defect with biochemical enzyme assay were included in the study. They were divided into 2 groups based on the OE results by funduscopy and were analyzed on the basis of their clinical features, biochemical test results, morphological analysis, and neuroimaging findings.ResultsThirty-seven (50%) of the 74 MD patients developed ophthalmologic symptoms. Abnormal findings were observed in 36 (48.6%) patients during an OE, and 16 (21.6%) of them had no ocular symptoms. Significantly higher rates of prematurity, clinical history of epilepsy or frequent apnea events, abnormal light microscopic findings in muscle pathology, diffuse cerebral atrophy in magnetic resonance imaging, and brainstem hyperintensity and lactate peaks in magnetic resonance spectroscopy were noted in the group with abnormal OE results.ConclusionAlthough the ophthalmologic symptoms are not very remarkable in MD patients, an OE is required. When the risk factors mentioned above are observed, a more active approach should be taken in the OE because a higher frequency of ocular involvement can be expected.

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified methods of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration.

Background: In East Asian countries, a prominent, long, and squared contour of the lower third of the face is considered unattractive, strong, and masculine. To change such a facial contour into an ovular contour, correction of the chin area is essential to accomplish the overall curve in the mandibuloplasty, and various methods for the horizontal reduction of the chin area have been suggested. The horizontal osteotomy and central strip resection technique, which is the most widely used method, has comparatively little effect and some restrictions. To improve these points, the authors introduced an effective method for simultaneously reducing the width and height of the chin without additional procedures. Methods: From March 2010 to May 2013, 432 women and 117 men underwent mandibular contouring surgery. Of these patients, 321 needed correction of the chin shape with simultaneous mandibular contouring surgery. Narrowing and vertical reduction genioplasty was performed for these patients using an inverted V-shaped osteotomy with central bony segment resection. Results: Narrowing and vertical reduction genioplasty was successfully performed in all cases. No severe complications were observed. Transient sensory changes of the skin around the chin were observed in 87 patients, but all recovered within 3 months. All of the patients were satisfied with the results. Conclusions: The method that we introduce in this article is a simple and more effective method for simultaneous reduction of the width and height of the chin without additional procedures. The square and long face was effectively and easily reshaped into a slender ovular contour, and the shape of the chin was changed from square to slender.