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Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the persistent fraction of infectivity at maximum neutralization, which may also influence preventive efficacy of active or passive immunization and the therapeutic outcome of the latter. Many NAbs neutralize HIV-1 CZA97.012, a clone of a Clade-C isolate, to ~100%. But here NAb PGT151, directed to a fusion-peptide epitope, left a persistent fraction of 15%. NAb PGT145, ligating the Env-trimer apex, left no detectable persistent fraction. The divergence in persistent fractions was further analyzed by depletion of pseudoviral populations of the most PGT151- and PGT145-reactive virions. Thereby, neutralization by the non-depleting NAb increased, whereas neutralization by the depleting NAb decreased. Furthermore, depletion by PGT151 increased sensitivity to autologous neutralization by sera from rabbits immunized with soluble native-like CZA97.012 trimer: substantial persistent fractions were reduced. NAbs in these sera target epitopes comprising residue D411 at the V4-β19 transition in a defect of the glycan shield on CZA97.012 Env. NAb binding to affinity-fractionated soluble native-like CZA97.012 trimer differed commensurately with neutralization in analyses by ELISA and surface plasmon resonance. Glycan differences between PGT151- and PGT145-purified trimer fractions were then demonstrated by mass spectrometry, providing one explanation for the differential antigenicity. These differences were interpreted in relation to a new structure at 3.4-Å resolution of the soluble CZA97.012 trimer determined by cryo-electron microscopy. The trimer adopted a closed conformation, refuting apex opening as the cause of reduced PGT145 binding to the PGT151-purified form. The evidence suggests that differences in binding and neutralization after trimer purification or pseudovirus depletion with PGT145 or PGT151 are caused by variation in glycosylation, and that some glycan variants affect antigenicity through direct effects on antibody contacts, whereas others act allosterically.

Abstract Introduction This study aimed to examine the reliability and validity of the Korean version of the Utrecht Grief Rumination Scale (UGRS) among healthcare workers who witnessed patient deaths. We also examined whether grief rumination may impact the cognitive‐behavioral model of hypochondriasis. Methods This study was conducted via an anonymous online survey targeting healthcare workers who had worked at a tertiary hospital and had witnessed patient deaths over the previous 2 years. Demographic data and responses to the UGRS, the Pandemic Grief Scale (PGS) for healthcare workers, the Stress and Anxiety to Viral Epidemic‐9 (SAVE‐9), the Obsession with COVID‐19 Scale (OCS), and the Coronavirus Reassurance‐Seeking Behaviors Scale (CRBS) were collected by requesting participants to recall their emotional state during the 2 weeks after witnessing a patient's death. Results The Korean version of the UGRS is reliable (Cronbach's alpha = 0.941) and valid (comparative fit index = 0.920, Tucker–Lewis index = 0.900, root‐mean‐square‐error of approximation = 0.102, standardized root‐mean‐square residual = 0.050) for measuring grief rumination in healthcare workers. The OCS was predicted by CRBS (β = 0.19, p

With the arrival of the era of big data, the conventional von Neumann architecture is now insufficient owing to its high latency and energy consumption that originate from its separated computing and memory units. Neuromorphic computing, which imitates biological neurons and processes data through parallel procedures between artificial neurons, is now regarded as a promising solution to address these restrictions. Therefore, a device with analog switching for weight update is required to implement neuromorphic computing. Resistive random access memory (RRAM) devices are one of the most promising candidates owing to their fast-switching speed and scalability. RRAM is a non-volatile memory device and operates via resistance changes in its insulating layer. Many RRAM devices exhibiting exceptional performance have been reported. However, these devices only excel in one property. Devices that exhibit excellent performance in all aspects have been rarely proposed. In this Research Update, we summarize five requirements for RRAM devices and discuss the enhancement methods for each aspect. Finally, we suggest directions for the advancement of neuromorphic electronics.

Introduction: Poor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown. Methods: We conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis. Results: A total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73–0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14–6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13–2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23–5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization. Conclusion: Several clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.

Purpose The aim of this study was to assess the diagnostic role of fine-needle aspiration cytology (FNAC) and analyze factors associated with false-negative FNAC results in patients with parathyroid incidentaloma who were referred for ultrasonography (US)-guided fine-needle aspiration (FNA) of thyroid nodules. Methods In this study, 121 patients with suspected parathyroid lesions were enrolled. The patients underwent US-guided FNAC with measurements of washout parathyroid hormone (PTH) between January 2015 and May 2020. The diagnostic performance of FNAC for the diagnosis of parathyroid lesions was assessed using surgical results and elevated washout PTH as a reference standard. The clinical and radiologic features associated with false-negative results on FNAC for the diagnosis of parathyroid lesions were evaluated. Results Among the 121 nodules assessed, 38 were parathyroid lesions (31.4%), and 83 were non-parathyroid lesions (68.6%). The diagnostic performance of FNAC for parathyroid incidentaloma showed a sensitivity of 31.6% (12/38), specificity of 100% (83/83), positive predictive values of 100% (12/12), negative predictive values of 76.1% (83/109), and accuracy of 78.5% (95/121). The FNAC results of non-parathyroid lesions included thyroid nodules, lymph nodes, neurogenic tumors, and fat tissue. True-positive results on FNAC were significantly associated with performing FNA twice (58.3% vs. 23.1%, P=0.043). Conclusion Considering the low sensitivity of FNAC, measuring washout PTH in addition to FNAC may help accurately diagnose parathyroid incidentaloma on thyroid US. Further, the falsenegative rate for FNAC can be reduced by obtaining two or more FNA samples.

Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

Abstract Auscultation is an important diagnostic method for lung diseases. However, it is a subjective modality and requires a high degree of expertise. To overcome this constraint, artificial intelligence models are being developed. However, these models require performance improvements and do not reflect the actual clinical situation. We aimed to develop an improved deep-learning model learning to detect wheezing in children, based on data from real clinical practice. In this prospective study, pediatric pulmonologists recorded and verified respiratory sounds in 76 pediatric patients who visited a university hospital in South Korea. In addition, structured data, such as sex, age, and auscultation location, were collected. Using our dataset, we implemented an optimal model by transforming it based on the convolutional neural network model. Finally, we proposed a model using a 34-layer residual network with the convolutional block attention module for audio data and multilayer perceptron layers for tabular data. The proposed model had an accuracy of 91.2%, area under the curve of 89.1%, precision of 94.4%, recall of 81%, and F1-score of 87.2%. The deep-learning model proposed had a high accuracy for detecting wheeze sounds. This high-performance model will be helpful for the accurate diagnosis of respiratory diseases in actual clinical practice.

Background To assess the effects of radiofrequency ablation (RFA) using an internally-cooled wet (ICW) electrode in ex vivo bovine liver and evaluate the feasibility of the ICW electrode for benign thyroid nodules.Methods We developed an 18-gauge ICW electrode with a microhole at the distal tip for tissue infusion of chilled (0 − 4 °C) isotonic saline (rate = 1.5 ml/min). RFA using ICW and IC electrodes were performed in bovine livers (40 pairs, 1-cm active tip, 50 W, 1-min). We compared the morphological characteristics of ablation zones and presence of carbonization. Twenty patients with benign thyroid nodules larger than 5 ml were prospectively enrolled in a clinical study and underwent ultrasound-guided RFA with ICW electrodes. Ultrasound examinations, laboratory data, and symptom and cosmetic scores were evaluated preprocedure and 1 and 6 months after the procedure.Results In the ex vivo study, the ICW achieved significantly larger ablation zones than the IC (p

In an effort to discover novel scaffolds of non-nucleotide-derived Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors to stimulate the Stimulator of Interferon Genes (STING) pathway, we designed and synthesised pyrrolopyrimidine and pyrrolopyridine derivatives and performed structure-activity relationship (SAR) study. We found 18p possessed high potency (IC50 = 25.0 nM) against ENPP1, and activated STING pathway in a concentration dependent manner. Also, in response to STING pathway activation, cytokines such as IFN-β and IP-10 were induced by 18p in a concentration dependent manner. Finally, we discovered that 18p causes inhibition of tumour growth in 4T1 syngeneic mouse model. This study provides new insight into the designing of novel ENPP1 inhibitors and warrants further development of small molecule immune modulators for cancer immunotherapy.

An optimum route to synthesis the W-based composite powders with homogeneous dispersion of oxide nanoparticles was investigated. The La2O3 dispersed W powder was synthesized by ultrasonic spray pyrolysis using ammonium metatungstate hydrate and lanthanum nitrate. The dispersion of Y2O3 nanoparticles in W- La2O3 powder was carried out by a polymer addition solution method using yttrium nitrate. XPS and TEM analyses for the composite powder showed that the nano-sized La2O3 and Y2O3 particles were well distributed in W powder. This study suggests that the combination processing of ultrasonic spray pyrolysis and polymeric additive solution is a promising way to synthesis W-based composite powders.

Background: The osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available β-tricalcium phosphate (β-TCP) regarding their potential to accelerate bone formation in defective rat tibias. Methods: The specimens with OCP composite were manufactured into 5 ​mm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 ​mm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation. Results: In the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of β-TCP. However, differences were observed in the residual graft materials. Most β-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the β-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. β-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the β-TCP group. Conclusions: In this study, OCP/Alg was equivalent to β-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings. The Translational Potential of this Article: In our research, we compared our various manufactured OCP composites to commercially available β-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to β-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.

Background/purpose: Oral wound healing undergoes a dynamic process of oral environment. This study aimed to investigate the effects of hyaluronic acid (HA) film on oral wound healing in a rat model. Materials and methods: A total of 60 rats with tongue wounds (5 mm in diameter) were randomly divided into control (n = 20), HA gel (n = 20), and HA film groups (n = 20). The animals were sacrificed on either 3 or 7 days after the experiment. Clinical, histological, and quantitative reverse transcriptase-polymerase chain reaction analysis were performed to evaluate the healing rate, inflammation, re-epithelialization, and gene expression of wound healing biomarkers. Results: The healing rates of HA gel (84.4 ± 9.2%) and HA film (74.0 ± 15.0%) were significantly higher than that of the control (51.7 ± 16.9%) on day 7 (P

Abstract Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.

Recently, clinical trials of adeno-associated virus-mediated replacement therapy have suggested long-term therapeutic effects for several genetic diseases of the liver, including hemophilia. However, there remain concerns regarding decreased therapeutic effects when the liver is regenerated or when physiological proliferation occurs. Although genome editing using the clustered regularly interspaced short palindromic repeats/Cas9 system provides an opportunity to solve this problem, low knock-in efficiency may limit its application for therapeutically relevant expression. Here, we identified a novel gene, APOC3, in which a strong promoter facilitated the expression of knocked-in genes in hepatocytes. We also investigated the effects of APOC3 editing using a small Cas9 protein derived from Campylobacter jejuni (CjCas9) in a hemophilic model. We demonstrated that adeno-associated virus-mediated delivery of CjCas9 and donor led to moderate levels of human factor 9 expression in APOC3-humanized mice. Moreover, knock-in-driven expression induced substantial recovery of clotting function in mice with hemophilia B. There was no evidence of off-target editing in vitro or in vivo. Collectively, our findings demonstrated therapeutically relevant expression using a precise and efficient APOC3-editing platform, providing insights into the development of further long-term therapeutics for diverse monogenic liver diseases.

Presumed idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure with unknown etiology, and 10% of cases occur secondarily to cerebral venous sinus thrombosis (CVST). CVST may be underestimated when findings of IIH are missed in a normal-weight patient without risk factors of coagulopathy. Here, we present a case of CVST that mimics a neurogenic tumor in the hypoglossal canal in a normal-weight patient without risk factors of coagulopathy.

A granular cell tumor (GCT) is a rare soft tissue tumor that usually arises from the striated muscle of the tongue. Few literatures have reported pectoral muscle involvement of the GCT. Herein, we report a rare case of a GCT originating from the pectoral muscle below the breast with multimodal imaging appearance.

Abstract Hydrogen evolution reaction (HER) is a promising clean and sustainable energy source with zero carbon emissions. Numerous studies have been conducted with versatile low dimensional materials, and the development of highly active electrochemical catalysts for HER is one of the most important applications of the materials in these studies. Despite such extensive research, the physical origin of the active catalytic performance of low dimensional materials remains unclear, and is distinguished from that of classical transition metal‐based catalysts. Here, recent studies on the intrinsic catalytic activity of 2D semimetals are reviewed, particularly among transition metal dichalcogenides (TMDs), highlighting promising strategies for the design of materials to further enhance their catalytic performance. One attractive approach for active HER involves fabricating single‐atom catalysts in the framework of TMDs. The electrochemical reaction at a catalytic atom for hydrogen evolution has typically been described by the Sabatier principle. Recent studies have focused on optimizing the Gibbs free energy for hydrogen adsorption via down‐sizing, alloying, hybridizing, hetero‐structuring, and phase boundary engineering, mostly with TMDs. The unique advantages of TMDs and their derivatives for HER are summarized, suggesting promising research directions for the design of low dimensional electrochemical catalysts for efficient HER and their energy applications.

Abstract In the upcoming ubiquitous era, wearable/flexible electronics are spotlighted to get various types of numerous information in real time. Several researchers have investigated flexible materials, and developed diverse thin‐film transfer methods. However, there are some limitations of the intrinsic material unstabilities, and low production yield. Here, light‐induced thin‐film transfer methods are reported by using new transfer mechanism of phase transition in sacrificial materials. Lift‐off conditions with high‐energy laser are delicately optimized by theoretical calculations and experiments to minimize mechanical/thermal damages of the upper thin‐film devices. The selected sacrificial materials of GeSbTe (GST) and indium tin oxide (ITO) with the 300 nm thickness are delaminated from a transparent and rigid glass substrate by irradiating the excimer laser to the surface of the sacrificial layer. The laser‐based exfoliation mechanism of GST and ITO films are comprehended by various material surface analyses. Eventually, flexible oxide thin‐film transistors (TFTs) are successfully demonstrated through light‐induced exfoliation process, showing the usability of the developed transfer technique to future practical applications.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.

Chiral plasmonic nanoparticles are of great interest in nanotechnology. Here, the authors demonstrate chiral shape guidance by single-stranded oligonucleotides during particle growth based on sequence-specific hydrogen bonding within the strand.

Although differentiated thyroid cancer has an excellent prognosis and low mortality, its recurrence rate has been reported to be very high. While surgery is recommended as the standard treatment for recurrent thyroid cancer, reoperation may increase the incidence of complications due to fibrosis and anatomical distortion. In patients with high surgical risk or those who refuse repeated surgery, ultrasonography-guided ablation techniques including radiofrequency ablation, ethanol ablation, and laser ablation are suggested as alternative treatments. In this manuscript, we introduce an anatomy-based management concept for radiofrequency ablation for recurrent thyroid cancer, and present a review of the relevant literature, including indications, basic techniques, clinical outcomes, and complications.

A selective sequencing method, termed SeeN-Seq, is presented to link morphological phenotypes to single-cell RNAseq using UV laser patterning of hydrogel porosity.

Abstract Developing bioelectronics that retains their long‐term functionalities in the human body during daily activities is a current critical issue. To accomplish this, robust tissue adaptability and biointerfacing of bioelectronics should be achieved. Hydrogels have emerged as promising materials for bioelectronics that can softly adapt to and interface with tissues. However, hydrogels lack toughness, requisite electrical properties, and fabrication methodologies. Additionally, the water‐swellable property of hydrogels weakens their mechanical properties. In this work, an intrinsically nonswellable multifunctional hydrogel exhibiting tissue‐like moduli ranging from 10 to 100 kPa, toughness (400–873 J m−3), stretchability (≈1000% strain), and rapid self‐healing ability (within 5 min), is developed. The incorporation of carboxyl‐ and hydroxyl‐functionalized carbon nanotubes (fCNTs) ensures high conductivity of the hydrogel (≈40 S m−1), which can be maintained and recovered even after stretching or rupture. After a simple chemical modification, the hydrogel shows tissue‐adhesive properties (≈50 kPa) against the target tissues. Moreover, the hydrogel can be 3D printed with a high resolution (≈100 µm) through heat treatment owing to its shear‐thinning capacity, endowing it with fabrication versatility. The hydrogel is successfully applied to underwater electromyography (EMG) detection and ex vivo bladder expansion monitoring, demonstrating its potential for practical bioelectronics.

IntroductionDuring the COVID-19 pandemic, healthcare workers (HCWs) have been exposed to higher levels of anxiety and psychological stress than the general population. Nurses who cared for COVID patients could not avoid repeated mourning as they witnessed the deaths of their patients. Therefore, tools are needed to evaluate whether there is adequate support for the grieving process of HCWs in both qualitative and quantitative manners.MethodsData from 229 nurses who witnessed the deaths of COVID-19 inpatients were analyzed using an online survey of nurses working in three tertiary hospitals. Factor analysis was conducted to validate the 10-item Korean version of Grief Support in Healthcare Scale (GSHCS). Stress and Anxiety to Viral Epidemics-9 was used to measure stress and anxiety caused by coronavirus, Generalized Anxiety Disorder-7 was used to measure overall anxiety, and Patient Health Questionnaire-9 was used for depression. Convergent validity correlation analysis was also performed with GSHCS.ResultsThe two-factor model showed a good fit for the 10-item GSHCS (χ2 = 35.233, df = 34, p = 0.410, CFI = 0.999, TLI = 0.990, RMSEA = 0.013, SRMR = 0.064). Cronbach’s alpha is 0.918 and McDonald’s omega is 0.913, suggesting that the 10-item version of the GSHCS is reliable for determining psychometric properties.ConclusionAccording to this study, the 10-item Korean version of the GSHCS is a reliable and valid measure of psychological support for grief among frontline nursing professionals who have witnessed the deaths of patients they cared for while working in COVID-19 inpatient wards. A two-factor model of the GSHCS has a good model fit and good convergent validity with other rating scales that measure viral anxiety, depression, and general anxiety.

IntroductionNurses have been repeatedly exposed to unexpected death and grief during COVID-19 pandemic, and it is necessary to provide grief support for the nurses who have experienced the loss of patients to COVID-19. We aimed to explore the reliability and validity of the Pandemic Grief Scale (PGS) for Healthcare Workers among frontline nursing professionals working in COVID-19 inpatient wards whose patients may have died.MethodsAn anonymous online survey was performed among frontline nursing professionals working in COVID-19 wards in three tertiary-level general hospitals in Korea between April 7 and 26, 2021. In total, 229 from participants who confirmed they had witnessed death of patients were employed for the statistical analysis. The survey included demographic characteristics and rating scales, including the Korean version of the PGS for Healthcare Workers, the Fear of COVID-19 scale, the Generalized Anxiety Disorder-7 items, and the Patient Health Questionnaire-9 items.ResultsThe single-factor structure of the Korean version of the PGS for Healthcare Workers showed good fits for the model. The scale had good internal consistency and convergent validity with other anxiety and depression scales.ConclusionThe Korean version of the PGS of Healthcare Workers was valid and reliable for measuring grief reactions among nursing professionals facing the pandemic. It will be helpful in evaluating the grief reaction of the healthcare workers and providing them with a psychological support system.

The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies (mAbs) and catalyze rational vaccine development. Traditional mAb discovery is a costly and labor-intensive process, although recent advances in single-cell genomics using emulsion microfluidics allow simultaneous processing of thousands of individual cells. Here we present a streamlined method for isolation and analysis of large numbers of antigen-specific B cells, including next generation antigen barcoding and an integrated computational framework for B cell multi-omics. We demonstrate the power of this approach by recovering thousands of antigen-specific mAbs, including the efficient isolation of extremely rare precursors of VRC01-class and IOMA-class broadly neutralizing HIV mAbs.

PURPOSE Performing a warm-up prior to a sports competition is essential for preventing injuries and maximizing subsequent performance. Passive warming has therefore received attention because it can effectively maintain an elevated muscle temperature (T m) after a warm-up. The present study aimed to investigate the effects of local passive warming (LPW) administered during the transition phase between active warm-up and isokinetic exercises. METHODS Eleven healthy men participated in this randomized crossover study. During the 30-minute transition period, a customized water-perfused warming pad was placed on the anterior thighs of the dominant legs (+3°C or +6°C based on the baseline skin temperature) or no intervention for the control group (CON). Subsequently, the total work, peak torque, and average power during isokinetic knee extensions (10 repetitions at a speed of 60°/sce) were measured. Using surface electromyography (EMG), the root mean square and mean frequency from the rectus femoris during knee extension were measured to assess neuromuscular activity. RESULTS Total work (+6°C 1,289.8±389.3 vs. CON 1,437.3±408.2 Nm, p =.042), peak torque (+6°C 146.0±33.3 vs. CON 162.9±37.9 Nm, p=.022), and average power (+6°C 77.7±19.8 vs. CON 90.2±25.3 W, p=.012) were lower in the LPW +6°C group than in the CON group. EMG RMS was lower in the LPW +6°C group than in the CON group (+6°C 58.4±22.3 vs. CON 78.6±33.0 % MVC, p =.005). MF was higher in the LPW +6°C group than in the CON group (+6°C 87.5±12.4 vs. CON 81.4±11.0 Hz, p=.016). CONCLUSIONS Local passive warming administered during the transition phase was not an appropriate strategy for boosting the performance of subsequent isokinetic exercises. Accordingly, the application of passive warming should be carefully chosen before exercise commences.

Background Intraoperative pulmonary aspiration is a rare but potentially fatal complication associated with various risk factors. Preoperative recognition of these risk factors can prevent aspiration events during general anesthesia or facilitate prompt corrective measures in patients experiencing this complication. Case A 70-year-old female patient with hypertension underwent bilateral total knee arthroplasty under general anesthesia. Despite using a midnight nothing-per-oral (NPO) protocol, an unpredictable intraoperative aspiration event occurred during anesthesia induction. A detailed evaluation of the patient’s medical history and subsequent diagnostic imaging examinations indicated achalasia. She was treated for aspiration pneumonia for 2 weeks. After 2 months, rescheduled total knee arthroplasty was performed under spinal anesthesia without any complications. Conclusions Obtaining the patient’s medical history and assessing the risk factors are important to prevent unpredictable intraoperative pulmonary aspiration. High-risk patients should undergo adequate preoperative fasting and regional anesthesia or rapid-sequence intubation should be considered for safe induction of general anesthesia.

Abstract We aimed to confirm the reliability of the results of bi-parametric magnetic resolution imaging-ultrasound fusion targeted and systematic biopsies (bpMRI-US transperineal FTSB) compared to prostatectomy specimens. We retrospectively analyzed the records of 80 men who underwent bpMRI-US transperineal FTSB with region of interest (ROI) and subsequent robot-assisted radical prostatectomy. Changes in the grade group determined by MRI and biopsy versus surgical specimens were analyzed. Thirty-five patients with insignificant prostate cancer and 45 with significant cancer were diagnosed using bpMRI-US transperineal FTSB. Among those with insignificant PCa, 25 (71.4%) were upgraded to significant PCa in prostatectomy specimens: 9/12 (75.0%) with Prostate Imaging Reporting and Data System (PI-RADS) 3, 12/16 (75.0%) with PI-RADS 4, and 4/7 (57.1%) with PI-RADS 5. In the PI-RADS 3 group, the upgraded group showed higher prostate specific antigen (PSA) and PSA density (PSAD) than the concordance group; PSA 8.34(2.73) vs. 5.31(2.46) (p = 0.035) and PSAD 0.29(0.11) vs. 0.18(0.09) (p = 0.025). The results of prostate biopsy and prostatectomy specimens were inconsistent and underestimated in patients with MRI-visible lesions. Therefore, for precise and individualized treatment strategies for PCa with MRI-visible lesions, careful interpretation of biopsy result is required.

Metallic and dielectric nanoscatterers are optical pigments that offer rich resonating coloration in the subwavelength regime with prolonged material consistency. Recent advances in responsive materials, whose mechanical shapes and optical properties can change in response to stimuli, expand the scope of scattering-based colorations from static to active. Thus, active color-changing pixels are achieved with extremely high spatial resolution, in conjunction with various responsive polymers and phase-change materials. This review discusses recent progress in developing such responsive photonic nanopixels, ranging from electrochromic to other color-changing concepts. We describe what parameters permit modulation of the scattering colors and highlight superior functional devices. Potential fields of application focusing on imaging devices, including active full-color printing and flexible displays, information encryption, anticounterfeiting, and active holograms, are also discussed.

Abstract Anti-dementia medications are widely prescribed to patients with Alzheimer’s dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format—the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009–2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-d-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

This study aimed to discover the quantitative trait loci (QTL) associated with a high seed protein content in soybean and unravel the potential candidate genes. We developed two recombinant inbred line populations: YS and SI, by crossing Saedanbaek (high protein) with YS2035-B-91-1-B-1 (low protein) and Saedanbaek with Ilmi (low protein), respectively, and evaluated the protein content for three consecutive years. Using single-nucleotide polymorphism (SNP)-marker-based linkage maps, four QTLs were located on chromosomes 15, 18, and 20 with high logarithm of odds values (5.9–55.0), contributing 5.5–66.0% phenotypic variance. In all three experimental years, qPSD20-1 and qPSD20-2 were stable and identified in overlapping positions in the YS and SI populations, respectively. Additionally, novel QTLs were identified on chromosomes 15 and 18. Considering the allelic sequence variation between parental lines, 28 annotated genes related to soybean seed protein—including starch, lipid, and fatty acid biosynthesis-related genes—were identified within the QTL regions. These genes could potentially affect protein accumulation during seed development, as well as sucrose and oil metabolism. Overall, this study offers insights into the genetic mechanisms underlying a high soybean protein content. The identified potential candidate genes can aid marker-assisted selection for developing soybean lines with an increased protein content.

To dynamically identify malicious behaviors of millions of Windows malware, anti-virus vendors have widely been using sandbox-based analyzers. However, the sandbox-based analysis has a critical limitation that anti-analysis techniques (i.e., Anti-sandbox and Anti-VM techniques) can easily detect analyzers and evade from being analyzed. In this work, we study on anti-analysis techniques used in real-world malware. First off, to measure how many Windows malware exhibits anti-analysis techniques, we collect anti-analysis techniques used in malware. We, then, design and implement an automated system, named EvDetector, that detects malware which employ anti-analysis techniques. EvDetector finds if malware uses an anti-analysis technique and monitors whether the malware changes its execution paths based on the result of the anti-analysis technique. By using EvDetector, we analyzed 763,985 real-world malware that emerged from 2017 to 2020. Our evaluation results show that 16.21% of malware use anti-analysis techniques on average. Also, we check the effectiveness of the analysis result by comparing EvDetector and static analysis. EvDetector analyzes up to 49.88% of malware detected by static analysis did not use anti-analysis techniques. In addition, we analyze that only up to 3.75% of the packed malware used anti-analysis techniques. Finally, we analyze the evasive malware trend through familial analysis and behavioral analysis. Our work implies that the research community needs to put more effort on defeating such anti-analysis techniques to automatically analyze emerging malware and respond with them.

Purpose Radiofrequency ablation (RFA) and ethanol ablation (EA) are effective and safe for benign symptomatic thyroid nodules (BSTNs). However, relatively little is known about the effects of these procedures on patients’ quality of life (QoL). This prospective, multicenter study evaluated the effects of RFA and EA on changes in thyroid-specific QoL in patients with BSTNs and assessed the volume reduction and safety of these procedures. Methods Eighty-six consecutive patients with 86 BSTNs were prospectively included from two medical centers. RFA was performed for 55 BSTNs with solidity ≥50% and EA was performed for 31 BSTNs with solidity

To handle relentlessly emerging Android malware, deep learning has been widely adopted in the research community. Prior work proposed deep learning-based approaches that use different features of malware, and reported a high accuracy in malware detection, i.e., classifying malware from benign applications. However, familial analysis of real-world Android malware has not been extensively studied yet. Familial analysis refers to the process of classifying a given malware into a family (or a set of families), which can greatly accelerate malware analysis as the analysis gives their fine-grained behavioral characteristics. In this work, we shed light on deep learning-based familial analysis by studying different features of Android malware and how effectively they can represent their (malicious) behaviors. We focus on string features of Android malware, namely the Abstract Syntax Trees (AST) of all functions extracted from each malware, which faithfully represent all string features of Android malware. We thoroughly study how different string features, such as how security-sensitive APIs are used in malware, affect the performance of our deep learning-based familial analysis model. A convolutional neural network was trained and tested in various configurations on 28,179 real-world malware dataset appeared in the wild from 2018 to 2020, where each malware has one or more labels assigned based on their behaviors. Our evaluation reveals how different features contribute to the performance of familial analysis. Notably, with all features combined, we were able to produce up to an accuracy of 98% and a micro F1-score of 0.82, a result on par with the state-of-the-art.

Objective This study aimed to clarify the relative prognostic value of each History, Electrocardiography, Age, Risk Factors, and Troponin (HEART) score component for major adverse cardiac events (MACE) within 3 months and validate the modified HEART (mHEART) score. Methods This study evaluated the HEART score components for patients with chest symptoms visiting the emergency department from November 19, 2018 to November 19, 2019. All components were evaluated using logistic regression analysis and the scores for HEART, mHEART, and Thrombolysis in Myocardial Infarction (TIMI) were determined using the receiver operating characteristics curve. Results The patients were divided into a derivation (809 patients) and a validation group (298 patients). In multivariate analysis, age did not show statistical significance in the detection of MACE within 3 months and the mHEART score was calculated after omitting the age component. The areas under the receiver operating characteristics curves for HEART, mHEART and TIMI scores in the prediction of MACE within 3 months were 0.88, 0.91, and 0.83, respectively, in the derivation group; and 0.88, 0.91, and 0.81, respectively, in the validation group. When the cutoff value for each scoring system was determined for the maintenance of a negative predictive value for a MACE rate >99%, the mHEART score showed the highest sensitivity, specificity, positive predictive value, and negative predictive value (97.4%, 54.2%, 23.7%, and 99.3%, respectively). Conclusion Our study showed that the mHEART score better detects short-term MACE in high-risk patients and ensures the safe disposition of low-risk patients than the HEART and TIMI scores.

Abstract Neonatal jaundice is a very common disease in newborns and can lead to brain damage or death in severe cases. Phototherapy with light‐emitting diode (LED) arrays is widely used as the easiest and fastest way to relieve jaundice in newborns, but it has distinct disadvantages such as loss of water in the patient, damage to the retina, and separation from parents. In this paper, a novel light source‐based phototherapy for neonatal jaundice is proposed using a textile‐based wearable organic light‐emitting diode (OLED) platform that can move flexibly and conform to the curvature of the human body. The soft and flexible textile‐based blue OLED platform is designed to have a peak wavelength of 470 nm, suitable for jaundice treatment, and shows performance (>20 µW cm−2 nm−1) suitable for intensive jaundice treatment even at low voltage (

Abstract Background To evaluate the current status of emotional exhaustion and peritraumatic distress of healthcare workers (HCWs) in the COVID-19 pandemic, and identify factors associated with their mental health status. Methods An online survey involving 1068 of consented HCWs that included nurses, physicians, and public health officers was conducted in May 2020. Descriptive statistics and multivariate regression analyses were performed on the collected data. Results Although no significant difference in peritraumatic distress was observed among the surveyed HCWs, the workers’ experience of emotional exhaustion varied according to work characteristics. Respondents who were female, older, living with a spouse, and/or full-time workers reported higher levels of emotional exhaustion. Public health officers and other medical personnel who did not have direct contact with confirmed patients and full-time workers had a higher level of peritraumatic distress. Forced involvement in work related to COVID-19, worry about stigma, worry about becoming infected, and perceived sufficiency of organizational support negatively predict emotional exhaustion and peritraumatic distress. Conclusions Job-related and emotional stress of HCWs should not be neglected. Evidence-based interventions and supports are required to protect HCWs from mental illness and to promote mental health of those involved in the response to the COVID-19 pandemic.

Purpose: Androgens are steroid hormones that are very important in the sexual development and the maintenance of male reproductive system, and also have diverse actions in non-reproductive tissues, including potent antioxidant capacity. Type 2 diabetes mellitus is caused by tissue insulin resistance and insufficient insulin secretion from the pancreatic β-cells. The progressive decline of pancreatic β-cells in diabetes is closely related with the severity of disease. We wanted to know whether dihydrotestosterone (DHT) can protect insulin secreting pancreatic β-cells from apoptosis and accelerated senescence induced by oxidative stress. Materials and Methods: Cultured INS-1 cells were used. Various concentrations of H2O2 were applied to exert oxidative stresses. The degrees of apoptosis, accelerated senescence, and the changes of the expressions of related signaling molecules after the application of DHT were analyzed by CCK-8, p16 expression, SA-β-Gal staining, reverse transcription polymerase chain reactions and Western blots. Results: The application of H2O2 significantly increased (p

Abstract Background The aim of this study was to investigate the effect of combining immunohistochemical profiles and metabolic information to characterize breast cancer subtypes. Methods This retrospective study included 289 breast tumors from 284 patients who underwent preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). Molecular subtypes of breast cancer were classified as Hormonal, HER2, Dual (a combination of both Hormonal and HER2 features), and triple-negative (TN). Histopathologic findings and immunohistochemical results for Ki-67, EGFR, CK 5/6, and p53 were also analyzed. The maximum standardized uptake value (SUV) measured from FDG PET/CT was used to evaluate tumoral glucose metabolism. Results Overall, 182, 24, 47, and 36 tumors were classified as Hormonal, HER2, Dual, and TN subtypes, respectively. Molecular profiles of tumor aggressiveness and the tumor SUV revealed a gradual increase from the Hormonal to the TN type. The tumor SUV was significantly correlated with tumor size, expression levels of p53, Ki-67, and EGFR, and nuclear grade (all p

Abstract A successful HIV vaccine eliciting broadly neutralizing antibodies (bnAbs) must overcome the hurdle of being able to activate naive precursor B cells encoding features within their germline B cell receptors (BCR) that allow recognition of broadly neutralizing epitopes. Knowledge of whether bnAb precursor B cells are circulating at sufficient frequencies within individuals in communities heavily impacted by HIV may be important. Using a germline-targeting eOD-GT8 immunogen and high-throughput droplet-based single-cell BCR sequencing, we demonstrate that large numbers of paired BCR sequences from multiple donors can be efficiently screened to elucidate precursor frequencies of rare, naive VRC01-class B cells. Further, we analyzed IGHV1-2 allelic usage among three different cohorts; we find that IGHV1-2 alleles traditionally thought to be incompatible with VRC01-class responses are relatively common in various human populations and that germline variation within IGHV1-2 associates with gene usage frequencies in the naive BCR repertoire.

The nitrogen-vacancy (NV) centers in diamond have the ability to sense alternating-current (AC) magnetic fields with high spatial resolution. However, the frequency range of AC sensing protocols based on dynamical decoupling (DD) sequences has not been thoroughly explored experimentally. In this work, we aimed to determine the sensitivity of the ac magnetic field as a function of frequency using the sequential readout method. The upper limit at high frequency is clearly determined by Rabi frequency, in line with the expected effect of finite DD-pulse width. In contrast, the lower frequency limit is primarily governed by the duration of optical repolarization rather than the decoherence time (T2) of NV spins. This becomes particularly crucial when the repetition (dwell) time of the sequential readout is fixed to maintain the acquisition bandwidth. The equation we provide successfully describes the tendency in the frequency dependence. In addition, at the near-optimal frequency of 1 MHz, we reached a maximum sensitivity of 229 pT/Hz by employing the XY4-(4) DD sequence.

Heavy metal ions (HMIs) are exceedingly hazardous to both humans and the environment, and the necessity to eliminate them from aqueous systems prompted the development of novel materials. In this study, tris(2-benzimidazolylmethyl)amine (NTB) was impregnated into MIL-101-(Cr) metal-organic framework using an incipient wetness impregnation approach, and the ability of the composite material to adsorb Hg2+ ions from the water was examined. The synthesized materials were analyzed with several physico-chemical techniques such as powder X-ray diffraction, elemental analysis, scanning electron microscopy, thermogravimetric analysis, nitrogen sorption isotherms at 77 K, and X-ray photoelectron spectrometry. MIL-101-NTB quickly adsorbs 93.9% of Hg2+ ions within 10 min from a 10.0 ppm single ion solution. A better fit of the kinetic data to a pseudo-second-order model validated the chemisorption of Hg2+ ions on MIL-101-NTB. The experimental data fitted well with the Langmuir isotherm model, and the maximum adsorption capacity obtained at 125 ppm initial concentration was 111.03 mg/g. Despite the presence of other competing ions (Cu2+, Pb2+, and Cd2+), high Hg2+ ions removal efficiency (99.6%, 1.0 ppm initial concentration) was maintained in the diverse ion batch adsorption studies. A 0.2 M EDTA solution could desorb the Hg2+ ions, and cyclic Hg2+ ions sorption studies indicated that MIL-101-NTB might have a high Hg2+ ions removal efficiency for at least five consecutive cycles. Based on the FTIR and XPS analyses, Hg2+ ions chelation by NTB molecules and electrostatic interactions between Hg2+ ions and carboxylate groups in MIL-101-NTB are plausible mechanisms for Hg2+ ions adsorption.