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Rui Tian,1,* Hong Xun Ye,2,* Bao Guo Zhang,3 Dong Ying Gu,3 Bing Wen Zhang,1 Zhi Pan Teng,1 Mao Yong Jin,4 Jin Fei Chen,3 Jian Wei Qi1 1Department of E.N.T., Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, The People’s Hospital of Taixing, Taixing, 3Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 4Department of Technology, Nanjing Delta Biotechnology Co., Ltd., Nanjing, People’s Republic of China *These authors contributed equally to this work Purpose: Taxane-containing induction chemotherapy (IC) regimens in combination with concurrent chemoradiotherapy (CCRT) have been compared with non-taxane-containing IC combined with CCRT in randomized controlled trials (RCTs) in Chinese patients with advanced nasopharyngeal carcinoma (NPC). This meta-analysis aimed to systematically evaluate their clinical efficacy and safety profiling in this ethnic population.Methods: The electronic databases, PubMed, Embase, MEDLINE, and Chinese Biomedical Database, were searched for eligible studies. The outcomes included overall response rate (ORR), 1-year survival rate, and different types of adverse events. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.Results: A total of 12 RCTs (representing 835 patients) were identified. The pooled analysis showed that taxane-containing regimens had a significant improvement in ORR for nasopharyngeal lesion (OR =4.57, 95% CI =1.14–18.30, P=0.032, z=2.15) but not in cervical lymph nodes (OR =1.23, 95% CI =0.65–2.36, P=0.532, z=0.64) and in 1-year survival rates (OR =1.19, 95% CI =0.10–14.82, P=0.893, z=0.13) compared with non-taxane-containing regimens. Regarding the adverse events and toxicities, grade 3–4 leukopenia and neutropenia were significantly different between the two groups (P

Background/Aims: Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. Methods: The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. Results: In total, 676 patients were included, of whom 388 (57.4%) were male, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received

Numerous neuroimmunological disorders present with sleep-related symptoms. The identification of novel autoantibodies introduces new clinical categories in autoimmune diseases of the central nervous system and generates interest in the dynamic interaction between sleep and the immune system. In this review, the complex relationship among sleep, immune regulation, and neuroimmunological disorders was examined with emphasis on the vital role of sleep in modulating immune function and its influence on these conditions, This relationship emphasizes the importance of assessments and management of sleep quality in the treatment approaches for neuroimmunological disorders.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

Abstract Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells.

This paper proposes an ultra-wideband frequency-invariant beamforming (FIB) using a generalized nesting array. To implement ultra-wideband (9:1 bandwidth ratio) FIB with a reduced number of array elements, the target frequency band is divided into subbands. The subarrays have integer multiples of inter-element spacing of half-wavelength at the maximum frequency according to the bandwidth ratio of subbands. Due to this integer multiple relationships, the array elements of the subarrays are superimposed so that the total number of array elements is reduced while maintaining FIB performance over the target frequency band. Then, the FIB weights are derived based on the desired beam pattern using the inverse Fourier transform. A Bartlett beamformer is used to generate FIB patterns of the proposed nesting array. In addition, we investigate the interrelationship between the minimum required number of array elements and design parameters (target bandwidth, beamwidth, and side lobe level). For validation, 21 printed log-periodic dipole array antennas are fabricated and measured. The direction finding performance is evaluated and compared to that of a 35-element uniform linear array. The direction of arrival (DoA) estimation results of the proposed array show a root-mean-square error of less than 2.02° for an incident angle within ±50° when a signal-to-noise ratio is 10 dB. It is demonstrated that the proposed array exhibits ultra-wideband FIB performance similar to a conventional uniform linear array but with much fewer elements.

This paper proposes an optically transparent series-fed microstrip array with small inter-element spacing and stepped feed lines for antenna-on-display applications. In the proposed series-fed array, the inconsistency of resonant frequencies between the input impedance at the edge of the feed line and the consecutive patch element produces multiple resonant frequencies. The small inter-element spacing in the array reduces input impedance variation among multiple resonant frequencies so that they are closely spaced, forming a broad impedance bandwidth. Also, stepped feed lines allow for impedance matching by a gradual decrease in characteristic impedance. Thus, impedance bandwidth and flat gain of the antenna are enhanced as the number of array elements increases. Optical transparency of the antenna is realized by using thin-metal meshes to be implemented on an active area of display panels. To validate the proposed approach, a $5 \times 1$ array antenna is fabricated and measured. The measured results exhibit a -10 dB impedance bandwidth of 14.2% ( $25.08-28.92$ GHz) and 3 dB gain bandwidth of 10.1% ( $26.2-29$ GHz) with 7.02 dBi peak gain at 27.4 GHz. Furthermore, the design is extended to a $5 \times 4$ array with a feeding network, demonstrating the beam scanning properties of ±20° and ±40° at 28 GHz with a bore-sight gain of 11.8 dBi.

Background/Aims: Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea. Methods: We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association. Results: In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method. Conclusions: A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

BackgroundMyelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases.MethodsThe sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9).ResultsIn attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p

Abstract Dynamically controlling friction in micro- and nanoscale devices is possible using applied electrical bias between contacting surfaces, but this can also induce unwanted reactions which can affect device performance. External electric fields provide a way around this limitation by removing the need to apply bias directly between the contacting surfaces. 2D materials are promising candidates for this approach as their properties can be easily tuned by electric fields and they can be straightforwardly used as surface coatings. This work investigates the friction between single layer graphene and an atomic force microscope tip under the influence of external electric fields. While the primary effect in most systems is electrostatically controllable adhesion, graphene in contact with semiconducting tips exhibits a regime of unexpectedly enhanced and highly tunable friction. The origins of this phenomenon are discussed in the context of fundamental frictional dissipation mechanisms considering stick slip behavior, electron-phonon coupling and viscous electronic flow.

Abstract Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the central nervous system (CNS) with similar characteristics. The differential diagnosis between MS and NMOSD is critical for initiating early effective therapy. In this study, we developed a deep learning model to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI) data. The model was based on a modified ResNet18 convolution neural network trained with 5-channel images created by selecting five 2D slices of 3D FLAIR images. The accuracy of the model was 76.1%, with a sensitivity of 77.3% and a specificity of 74.8%. Positive and negative predictive values were 76.9% and 78.6%, respectively, with an area under the curve of 0.85. Application of Grad-CAM to the model revealed that white matter lesions were the major classifier. This compact model may aid in the differential diagnosis of MS and NMOSD in clinical practice.

Abstract 2D van der Waals (vdW) materials are emerging as the next generation platform for optical and electronic devices with their wide coverage of the energy bandgaps. The strong light–matter interactions in 2D vdW layers allow for exploring novel optical and electronic phenomena such as 2D polaritons exhibiting ultrahigh field confinement, defects‐induced new quantum states, and strain‐modulated quantum confinement of 2D excitons. Far‐field optical imaging techniques are extensively used to characterize the 2D vdW materials so far, however, subdiffraction spatial resolution is required for comprehensive investigations of 2D vdW materials of which physical properties are greatly influenced by local defects and strain. This article aims to cover historical advances, fundamental principles, and distinct features of emerging near‐field optical imaging techniques: scattering‐type scanning near‐field optical microscopy, tip‐enhanced Raman spectroscopy, tip‐enhanced photoluminescence techniques, and photo‐induced force microscopy. The recent developments toward spectroscopic analysis of near‐field imaging and applications for unveiling unique properties of 2D polaritons, nanoscale defects, and mechanical strains in 2D vdW materials, are also discussed. This review article provides an understanding of emerging near‐field imaging techniques and suggests prospective applications for exploring 2D vdW materials.

Abstract Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain–Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. In this prospective surveillance study of 38,828,691 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines.

This study evaluates the antibody responses to SARS-CoV-2 vaccines in patients with neuroimmunological disorders (pwNID) who are receiving immunomodulating treatments, compared to healthy individuals. It included 25 pwNID with conditions such as optic neuritis, neuromyelitis optica spectrum disorder, multiple sclerosis, myasthenia gravis, and polymyositis, as well as 56 healthy controls. All participants had completed their full SARS-CoV-2 vaccination schedule, and their blood samples were collected within six months of their last dose. The concentration of anti-SARS-CoV-2 IgG antibodies was measured using an enzyme-linked immunosorbent assay. The results showed that pwNID had significantly lower antibody titers (58.4 ± 49.2 RU/mL) compared to healthy individuals (81.7 ± 47.3 RU/mL). This disparity persisted even after adjusting for age and the interval between the final vaccination and sample collection. A notable correlation was found between the use of immunomodulating treatments and reduced antibody levels, whereas mRNA vaccines were linked to higher antibody concentrations. The conclusion of this study is that immunomodulating treatments may reduce the effectiveness of SARS-CoV-2 vaccines in pwNID. This insight is crucial for healthcare providers in designing vaccination strategies and managing treatment plans for pwNID on immunomodulating therapies, highlighting the need for personalized approaches in this subgroup.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.

Background/Aims Belching and retching tend to cause technical difficulties during endoscopic procedures; however, risk factors associated with belching and retching during endoscopy remain unclear. In this study, we investigated the factors associated with belching and retching during unsedated endoscopy and the effects of belching and retching on the grading of Los Angeles (LA) classification of reflux esophagitis. Materials and Methods This prospective observational study included patients who underwent unsedated esophagogastroduodenoscopy (EGD). We used a predefined grading system to evaluate belching and retching during the endoscopic examination. LA classification grades were compared between the endoscope insertion and withdrawal phases of EGD. Results The study included 327 patients. Age (specifically, young age [

Background/Aims: This study aimed to determine changes in endoscopist-driven sedation practices 5 years after the first nationwide survey in 2014 by the Korean Society of Gastrointestinal Endoscopy (KSGE). Methods: A 59-item survey covering current practices was electronically mailed to all members of the KSGE in 2019. Results: In total, 955 (12.8%) out of 7,486 questionnaires were returned. A total of 738 (77.7%) out of 955 respondents attended dedicated sedation education programs. The American Society of Anesthesiologists class was recorded by 464 (51.2%) out of 907 respondents. The recording rate was higher in respondents who completed sedation education (p=0.014) and worked in general or tertiary hospitals (p

Background Soft tissue defects of the multiple finger present challenges to reconstruction surgeons. Here, we introduce the use of a lateral arm free flap and syndactylization for the coverage of multiple finger soft tissue defects. Methods This retrospective study was conducted based on reviews of the medical records of 13 patients with multiple soft tissue defects of fingers (n = 33) that underwent temporary syndactylization with a microvascular lateral arm flap for temporary syndactylization from January 2010 to December 2020. Surgical and functional outcomes, times of flap division, complications, and demographic data were analyzed. Results Middle fingers were most frequently affected, followed by ring and index fingers. Mean patient age was 43.58 years. The 13 patients had suffered 10 traumas, 2 thermal burns, and 1 scar contracture. Release of temporary syndactyly was performed 3 to 9 weeks after syndactylization. All flaps survived, but partial necrosis occurred in one patient, who required a local transposition flap after syndactylization release. The mean follow-up was 15.8 months. Conclusion Coverage of multiple finger defects by temporary syndactylization using a free lateral arm flap with subsequent division offers an alternative treatment option.

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.

Abstract Background Glioblastoma (GBM) is the most aggressive type of brain tumor with heterogeneity and strong invasive ability. Treatment of GBM has not improved significantly despite the progress of immunotherapy and classical therapy. Epidermal growth factor receptor variant III (EGFRvIII), one of GBM-associated mutants, is regarded as an ideal therapeutic target in EGFRvIII-expressed GBM patients because it is a tumor-specific receptor expressed only in tumors. Flagellin B (FlaB) originated from Vibrio vulnificus, is known as a strong adjuvant that enhances innate and adaptive immunity in various vaccine models. This study investigated whether FlaB synergistically could enhance the anti-tumor effect of EGFRvIII peptide (PEGFRvIII). Methods EGFRvIII-GL261/Fluc cells were used for glioblastoma-bearing mouse brain model. Cell-bearing mice were inoculated with PBS, FlaB alone, PEGFRvIII alone, and PEGFRvIII plus FlaB. Tumor growth based on MRI and the survival rate was investigated. T cell population was examined by flow cytometry analysis. Both cleaved caspase-3 and CD8 + lymphocytes were shown by immunohistochemistry (IHC) staining. Results The PEGFRvIII plus FlaB group showed delayed tumor growth and increased survival rate when compared to other treatment groups. As evidence of apoptosis, cleaved caspase-3 expression and DNA disruption were more increased in the PEGFRvIII plus FlaB group than in other groups. In addition, the PEGFRvIII plus FlaB group showed more increased CD8 + T cells and decreased Treg cells than other treatment groups in the brain. Conclusions FlaB can enhance the anti-tumor effect of PEGFRvIII by increasing CD8 + T cell response in a mouse brain GBM model.

BackgroundThe detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes.MethodsWe conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated.ResultsFifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope.ConclusionWe developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes.

The discovery of novel autoantibodies in neurological disorders contributes to a better understanding of its pathogenesis, improves the accuracy of diagnosis, and leads to new treatment strategies. Advances in techniques for the screening and detection of autoantibodies have enabled the discovery of new antibodies in the central nervous system (CNS) and neuromuscular diseases. Cell-based assays using live or fixed cells overexpressing target antigens are widely used for autoantibody-based diagnosis in clinical practice. Common pathogenic autoantibodies are unknown in most patients with multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Novel pathogenic autoantibodies to aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) have been identified in neuromyelitis optica spectrum disorder and MOG antibody-associated disease, respectively. These diseases have clinical similarities to MS, but with the discovery of pathogenic autoantibodies, they are now recognized as distinct disease entities. Antibodies to paranodal membrane proteins such as neurofascin-155, contactin‑1, contactin‑associated protein‑1 in CIDP and muscle-specific kinase and low-density lipoprotein receptor–related protein 4 in myasthenia gravis were added to the profiles of autoantibodies in neurological disorders. Despite the relatively low frequency of seropositivity, autoantibody detection is currently essential for the clinical diagnosis of CNS and neuromuscular autoimmune disorders, and differential approaches to seropositive patients will contribute to more personalized medicine. We reviewed recent discoveries of autoantibodies and their clinical implications in CNS and neuromuscular disorders.

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Such cardiopulmonary complications are usually temporary, and most patients recover without sequelae. However, these events may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

Abstract A hole‐type vertical structure is adopted to fabricate a vertically stacked resistive switching random access memory (ReRAM) array. The vertical configuration is more advantageous in lowering the process cost and increasing integration density than the horizontal configuration. However, the memory cells constituting the hole‐type vertical‐ReRAM (V‐ReRAM) array can be short‐circuited if a middle electrode is introduced to stack a rectifying element onto the memory layer. Thus, a self‐rectifying Pt/Ta2O5/Al‐doped HfO2/TiN ReRAM is adopted in this study to prevent the sneak‐current and short‐circuit issues for efficient operation in vertical crossbar array configuration. A two‐ or three‐layer stacked V‐ReRAM is fabricated, and its electrical characteristics are evaluated. High switching uniformity and sufficiently large memory window and rectification ratio are acquired. The low operation power and high switching uniformity render this V‐ReRAM array suitable for high‐capacity storage devices. However, the on‐state data retention needs improvement. Detailed investigation of the three‐layer stacked device identifies that lateral charge spreading between neighboring cells in the V‐ReRAM causes such a problem, which can be mitigated by increasing the intercell distance.

Abstract Although fatigue is a major symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), the underlying mechanism remains unclear. We explored the relationship between subcortical structures and fatigue severity to identify neural substrates of fatigue in NMOSD. Clinical characteristics with brain magnetic resonance imaging were evaluated in forty patients with NMOSD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) questionnaire (a higher score indicates less fatigue). We assessed the correlation between subcortical structures and fatigue severity using surface-based shape analysis. Most of the enrolled patients showed fatigue (72.5%; mean FACIT-fatigue score, 34.8 ± 10.8). The FACIT-fatigue score was negatively correlated with Expanded Disability Status Scale and Beck Depression Inventory scores (r = − 0.382, p = 0.016; r = − 0.578, p

Bilateral pectoralis major myocutaneous (PMMC) flaps are commonly used to reconstruct large chest wall defects. We report a case of large chest wall defect reconstruction using bilateral PMMC flaps augmented with axillary V-Y advancement rotation flaps for additional flap advancement. A 74-year-old male patient was operated on for recurrent glottic squamous cell carcinoma. Excision of the tumor resulted in a 10×10 cm defect in the anterior chest wall. Bilateral PMMC flaps were raised to cover the chest wall defect. For further flap advancement, V-Y rotation advancement flaps from both axillae were added to allow complete closure. All flaps survived completely, and postoperative shoulder abduction was not limited (100° on the right side and 92° on the left). Age-related skin redundancy in the axillae enabled the use of V-Y rotation advancement flaps without limitation of shoulder motion. Bilateral PMMC advancement flaps and the additional use of V-Y rotation advancement flaps from both axillae may be a useful reconstructive option for very large chest wall defects in older patients.

Background/Aims: Fever is a common symptom of acute pancreatitis (AP). This study examined the factors associated with fever due to pancreatic inflammation in the early stages of non-biliary AP. Methods: This study analyzed the AP database from Kangwon National University Hospital from January 2018 until April 2021 and identified patients who developed fever within 1 week of hospitalization. Patients with gallstone pancreatitis, pseudocyst, walled-off necrosis, chronic pancreatitis, bacteremia, and other site infections were excluded. The febrile group was compared with the afebrile group. Results: One hundred and fifty-two patients were analyzed, and fever was diagnosed in 79 patients (52.0%). Based on multivariate analysis, fever was positively correlated with hypertriglyceridemia-induced AP (OR 16.8, 95% CI 4.0-70.7, p

Jaundice is a rare symptom of the paraneoplastic syndrome associated with prostate cancer. We report a case of metastatic prostate cancer that presented as jaundice. There was an absence of biliary obstruction and hepatic metastasis; therefore, the paraneoplastic syndrome was suggested as the etiology of cholestasis. Jaundice improved with the treatment of prostate cancer. In the literature, interleukin-6 has been suggested to be associated with paraneoplastic syndrome.

Background and AimCurrent therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling.MethodsTwenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud.ResultsThe alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group.ConclusionOur study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.

This paper proposes four methods and empirical formulas of adjusting characteristic impedances for thin-metal mesh transmission lines. The characteristic impedances are discretely adjusted by changing the number and the size of unit meshes, which provides macro-tuning capability, and the discrete values can be tuned more precisely by varying the thin-metal line width and the aspect ratio of mesh geometry. The validity of proposed methods is confirmed by full-wave numerical simulations, and the simulated impedance variations are well-described by our empirical formulas. For further verifications, 26 distinguished samples of thin-metal mesh transmission lines and a 28-GHz thin-metal mesh antenna are fabricated, and their characteristics are measured in millimeter-wave spectrums. The measured results confirm that the proposed methods and empirical formulas can provide accurate and more flexible design rules for impedance adjustment, which allows potential advances in display-integrated antenna applications.

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

Background/Aims: The utilization of endoscopic retrograde cholangiopancreatography (ERCP) is variable and largely dependent on a patient’s age, sex, and region. Herein we analyzed the publicly available Health Insurance Review and Assessment (HIRA) database with the aim of understanding the current status and trend of ERCP use in Korea. Methods: Between 2013 and 2017, information regarding ERCP was acquired from the HIRA database using the procedural codes of the Korean Standard Classification of Disease. We analyzed the annual number of patients according to age in 10- year increments, sex, type of medical institution, and administrative division. Results: The total number of patients and number of patients undergoing ERCP per 100,000 people increased from 40,516 and 78.6 in 2013 to 47,027 and 91.3 in 2017, respectively those aged 70 years accounted for the highest number, and the increase was the most prominent in those aged 80 years or older. Men underwent more ERCPs than women, except in younger patients (

BackgroundAfter gastrectomy, patients may experience the postgastrectomy syndrome and face difficulties adapting to everyday diet. Recently, human health coaching via a mobile application (app) has been used for obese patients or patients with chronic diseases, with significant improvements in clinical outcomes. The aim of this study is to evaluate and compare the effects of human health coaching via a mobile app and conventional face-to-face counseling in patients who underwent gastrectomy for gastric cancers.MethodsThis study is a single-institution, prospective randomized controlled trial comparing the mobile health and face-to-face counselling groups. After randomization, participants assigned to the mobile health coaching group will receive health coaching via a mobile app for 3 months after discharge, and the assigned coaches will provide personalized advice based on the self-recorded health data. Participants in the face-to-face group will have 1- and 3-months postoperative dietary consultations with a clinical dietitian. The primary endpoint is the food restriction score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-STO22, and secondary endpoints included all other quality of life scale scores and nutritional parameters. The calculated sample size is 180, and the outcomes will be measured until 1-year post-surgery.SignificanceThis study will show the efficacy of human health coaching via a mobile app on dietary adaptation in patients who underwent gastrectomy. A relational approach based on personal data and timely intervention using a mobile platform could reduce patients' trial and error and improve quality of life.Trial registrationClinicalTrials.gov, NCT04394585, Registered 19 May, 2020 -Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT040394585.

Herein, a true random number generator (TRNG) based on a CuxTe1−x diffusive memristor (DM) using its threshold switching (TS) behavior is reported. The intrinsic stochasticity of the TS behavior contributes to the randomness of the TRNG system. The switching behavior is discussed through field‐induced nucleation theory and surface diffusion dynamics. Demonstrating the performance of TRNG as a hardware security application, the DM‐based TRNG passes all 15 National Institute of Standards and Technology randomness tests without any post‐processing step, even in high‐temperature conditions. Moreover, a nonlinear‐feedback shift register is implemented for a high‐speed TRNG, producing the highest rate among the reported volatile‐memristor‐based TRNGs.

BackgroundClear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate.Objective and MethodsPatients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D3 (serum 25(OH)D3) were explored. The impact of 1,25(OH)2D3 stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated.ResultsIn both MS and NMOSD, stimulation of PBMCs with 1,25(OH)2D3 followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19+CD27+ memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)2D3 was negatively correlated with serum 25(OH)D3 in MS (Spearman’s ρ=–0.594, p=0.042), but positively correlated in NMOSD (Pearson’s r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19+CD24+CD38+ regulatory B cells and serum 25(OH)D3 in either MS or NMOSD. In addition, the level of 1,25(OH)2D3-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D3 (for ΔCT, r=0.744, p=0.014) in MS.ConclusionThese findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D3 and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a rare but critical disease with a high mortality rate. The diagnostic dilemma of PPP syndrome is the fact that symptoms occur unexpectedly. A 48-year-old man presented with fever and painful swelling of the left foot that was initially mistaken for cellulitis and gouty arthritis. The diagnosis of PPP syndrome was made based on the abdominal CT findings and elevated pancreatic enzyme levels, lobular panniculitis with ghost cells on a skin biopsy, and polyarthritis on a bone scan. The pancreatitis and panniculitis disappeared spontaneously over time, but the polyarthritis followed its own course espite the use of anti-inflammatory agents. In addition to this case, 30 cases of PPP syndrome in the English literature were reviewed. Most of the patients had initial symptoms other than abdominal pain, leading to misdiagnosis. About one-third of them were finally diagnosed with a pancreatic tumor, of which pancreatic acinar cell carcinoma was the most dominant. They showed a mortality rate of 32.3%, associated mainly with the pancreatic malignancy. Therefore, PPP syndrome should be considered when cutaneous or osteoarticular manifestations occur in patients with pancreatitis. Active investigation and continued observations are needed for patients suspected of PPP syndrome.

Actinomycosis can mask malignant diseases. This paper reports a case of colonic diffuse large B-cell lymphoma (DLBCL), which was misdiagnosed as abdominal actinomycosis. A 76-year-old woman presented with right flank pain and weight loss. Abdominal CT and colonoscopy revealed a huge ascending colon mass. Despite the initial impression of a malignancy, a colonoscopic biopsy revealed no malignant cells, but sulfur granules and a filamentous organism suggesting actinomycosis. Intravenous penicillin G was administered under the impression of abdominal actinomycosis but her condition deteriorated rapidly. Follow up CT showed markedly increased colon mass and new multiple nodular lesions around the ascending colon. Sono-guided percutaneous biopsy of the nodular lesion was performed. The pathological result was DLBCL. The patient was scheduled to undergo chemotherapy but the patient expired due to cancer progression. The diagnosis of gastrointestinal infiltrating tumors is often difficult because a superficial biopsy usually does not provide a confirmative diagnosis. This case highlights the difficulty in making a correct diagnosis of lymphoma due to the concomitant actinomycosis. Malignant conditions must be considered in cases of actinomycosis with no response to antimicrobial therapy.

Pancreatic metastasis from cervical cancer is extremely rare. We report a case of metastatic adenocarcinoma of the pancreas from uterine cervical cancer. A 70-year-old woman was referred because of a pancreatic mass detected by CT. She had been diagnosed with uterine cervical adenocarcinoma 20 months previously. After concurrent chemoradiotherapy, CT showed no evidence of the cervical mass, and follow-up showed no evidence of recurrence. Endoscopic ultrasound-guided fine needle aspiration biopsy of the pancreatic mass resulted in a diagnosis of metastatic adenocarcinoma from uterine cervix.

Biocompatible β-Ca3(PO4)2 and mechanically stable t-ZrO2 composites are currently being combined to overcome the demerits of the individual components. A series of five composites were synthesized using an aqueous precipitation technique. Their structural and mechanical stability was examined through X-ray diffraction, Rietveld refinement, FTIR, Raman spectroscopy, high-resolution scanning electron microscopy, and nanoindentation. The characterization results confirmed the formation of β-Ca3(PO4)2–t-ZrO2 composites at 1100 °C. Heat treatment above 900 °C resulted in the degradation of the composites because of cationic interdiffusion between Ca2+ ions and O−2 vacancy in Zr4+ ions. Sequential thermal treatments correspond to four different fractional phases: calcium-deficient apatite, β-Ca3(PO4)2, t-ZrO2, and m-ZrO2. The morphological features confirm in situ synthesis, which reveals abnormal grain growth with voids caused by the upsurge in ZrO2 content. The mechanical stability data indicate significant variation in Young’s modulus and hardness throughout the composite.

Introduction: Highly pathogenic Asian H5-subtype avian influenza viruses have been found in poultry and wild birds worldwide since they were first detected in southern China in 1996. Extensive control efforts have not eradicated them. Vaccination prevents such viruses infecting poultry and reduces the number lost to compulsory slaughter. The study showed the efficacy of inactivated H5 vaccine from the H5N8 virus against highly pathogenic H5N8 and H5N6 avian influenza viruses in chickens.

In utero exposure to maternal immune activation (MIA) is an environmental risk factor for neurodevelopmental and neuropsychiatric disorders. Animal models provide an opportunity to identify mechanisms driving neuropathology associated with MIA. We performed time-course transcriptional profiling of mouse cortical development following induced MIA via poly(I:C) injection at E12.5. MIA-driven transcriptional changes were validated via protein analysis, and parallel perturbations to cortical neuroanatomy were identified via imaging. MIA-induced acute upregulation of genes associated with hypoxia, immune signaling, and angiogenesis, by 6 hr following exposure. This acute response was followed by changes in proliferation, neuronal and glial specification, and cortical lamination that emerged at E14.5 and peaked at E17.5. Decreased numbers of proliferative cells in germinal zones and alterations in neuronal and glial populations were identified in the MIA-exposed cortex. Overall, paired transcriptomic and neuroanatomical characterization revealed a sequence of perturbations to corticogenesis driven by mid-gestational MIA.

Purpose The composite autonomic symptom scale-31 (COMPASS-31) is a self-rated questionnaire that evaluates diverse autonomic symptoms. In the present study, we developed the Korean version of the COMPASS-31 (K-COMPASS-31) with appropriate translation, and verified its reliability and internal and external validity in patients with Parkinson’s disease (PD). Methods The original COMPASS-31 was translated independently into Korean by two bilingual neurologists. Test-retest reliability was evaluated at a 2-week interval. We investigated the correlations between the K-COMPASS-31, the scale for outcomes in PD-autonomic (SCOPA-AUT), and the results of an autonomic function test (AFT), respectively. Results A total of 90 patients with PD (47 females; mean age, 63.4 ± 10.8 years) were enrolled. The K-COMPASS-31 showed excellent test-retest reliability (intra-class correlation coefficient = 0.874, p < 0.001) and internal validity (Cronbach’s α-coefficient = 0.878). The COMPASS-31 was positively correlated with SCOPA-AUT (r = 0.609, p < 0.001) and the results of the AFT. Conclusions In conclusion, the K-COMPASS-31 showed excellent reliability and validity for the assessment of autonomic symptoms in PD patients. The K-COMPASS-31 is an easy-to-repeat and widely used tool for investigating autonomic dysfunction in various neurologic disorders and enables comparison of autonomic dysfunction among neurologic disorders. We recommend the K-COMPASS-31 as a valid instrument for use in clinical practice for patients with PD.

Despite class A ESBLs carrying substitutions outside catalytic regions, such as Cys69Tyr or Asn136Asp, have emerged as new clinical threats, the molecular mechanisms underlying their acquired antibiotics-hydrolytic activity remains unclear. We discovered that this non-catalytic-region (NCR) mutations induce significant dislocation of β3-β4 strands, conformational changes in critical residues associated with ligand binding to the lid domain, dynamic fluctuation of Ω-loop and β3-β4 elements. Such structural changes increase catalytic regions’ flexibility, enlarge active site, and thereby accommodate third-generation cephalosporin antibiotics, ceftazidime (CAZ). Notably, the electrostatic property around the oxyanion hole of Cys69Tyr ESBL is significantly changed, resulting in possible additional stabilization of the acyl-enzyme intermediate. Interestingly, the NCR mutations are as effective for antibiotic resistance by altering the structure and dynamics in regions mediating substrate recognition and binding as single amino-acid substitutions in the catalytic region of the canonical ESBLs. We believe that our findings are crucial in developing successful therapeutic strategies against diverse class A ESBLs, including the new NCR-ESBLs.

We report a case of acute pancreatitis secondary to pancreatic neuroendocrine tumor. A 46-year old man presented with upper abdominal pain. The serum amylase and lipase were elevated. Abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a 1.7 cm sized mass at the pancreas body with a dilatation of the upstream pancreatic duct and mild infiltrations of peripancreatic fat. An endoscopic ultrasound-guided fine needle biopsy was performed for the pancreatic mass, but only necrotic tissue was observed on the pathologic examination. A chest and neck CT scan revealed anterior mediastinal, paratracheal, and cervical lymph node enlargement, which were indicative of metastasis. An ultrasound-guided core needle biopsy was performed for the enlarged neck lymph node, and pathologic examination revealed a metastatic poorly differentiated carcinoma. Immunohistochemical analysis showed positive staining for synaptophysin, chromogranin A, and CD 56, indicative of a neuroendocrine carcinoma.

This paper proposes a pattern distortion coefficient as a new figure of merit to quantitatively evaluate both mutual coupling and pattern distortions in multi-antenna systems. The proposed coefficient is defined as a cross correlation between unaffected and affected far-field patterns of antennas under test, and the input patterns are weighted using a Gaussian function to consider the target operation angle. The feasibility of the proposed approach is validated using a two-antenna system composed of an inverted-F antenna and a microstrip patch antenna, and the amount of mutual coupling is adjusted by changing the distance between the two antennas. The evaluation is further extended to a single-antenna system with a conducting wall that produces strong platform effects with serious pattern distortions. The results demonstrate that the proposed figure of merit provides quantitative insight into the amplitude and phase distortions of far-field patterns that can be caused by both mutual coupling and platform effects.

Article: Randomised Controlled Trial of Long-term Maintenance Corticosteroid Therapy in Patients with Autoimmune Pancreatitis (Gut 2017;66:487-494)