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In a Phase III study, regdanvimab (CT-P59) reduced the risk of hospitalization or death versus placebo in patients with mild-to-moderate coronavirus disease 2019 (COVID-19).We performed a retrospective cohort study of patients with COVID-19 to examine the effect of regdanvimab versus standard of care (SoC) on oxygen saturation.We reviewed patients with mild-to-moderate COVID-19 confirmed by reverse transcription-polymerase chain reaction at a single hospital in the Republic of Korea. The primary efficacy end point was the proportion of patients deteriorating with peripheral capillary oxygen saturation94% on room air up to day 28.A total of 127 patients were treated for COVID-19 with regdanvimab, 190 with SoC. The proportion of patients deteriorating with peripheral capillary oxygen saturation94% on room air up to day 28 was 13.4% with regdanvimab and 39.5% with SoC (This real-world study indicates that regdanvimab can prevent deterioration in patients with mild-to-moderate COVID-19. (

Background Regdanvimab is a monoclonal antibody with activity against SARS-CoV-2. A Phase 2/3 study with two parts is currently ongoing and data up to Day 28 of Part 1 is available while the data from 1315 patients enrolled in Part 2 are expected in June 2021. Methods This phase 2/3, randomized, parallel-group, placebo-controlled, double-blind study with 2 parts is aimed to assess the therapeutic efficacy of regdanvimab in outpatients with mild to moderate COVID-19, not requiring supplemental oxygen therapy. Patients aged >18 with the onset of symptoms within 7 days were eligible to be enrolled. Results In Part 1, 307 patients (101, 103, and 103 patients in the regdanvimab 40 mg/kg, regdanvimab 80 mg/kg, and placebo groups, respectively) were confirmed to have COIVD-19 by RT-qPCR at Day 1 (or Day 2). Regdanvimab significantly reduced the proportion of patients who required hospitalization or supplemental oxygen therapy compared to placebo (8.7% in the placebo vs. 4.0% in the regdanvimab 40 mg/kg). The difference in events rate was even larger in patients who met the high-risk criteria and confirmed a 66.1% reduction in patients receiving regdanvimab 40 mg/kg (Table 1). The median time to clinical recovery was shortened by 2.9 days (7.18 days for regdanvimab 40 mg/kg and 10.03 days for placebo; high-risk). Also, greater reductions from baseline viral load were shown in regdanvimab groups (Figure 1). The safety results confirmed that the regdanvimab was safe and well-tolerated. Occurrence of adverse events (Table 2) and results of other safety assessments were generally comparable among the 3 groups. The overall rate of infusion-related reaction was low and no serious adverse events or deaths were reported. The anti-drug antibody positive rate was low in the regdanvimab groups (1.4% in regdanvimab vs. 4.5% in placebo), and no antibody-dependent enhancement was reported. Conclusion Results from the first part of the study indicate that regdanvimab may lower the rate of hospitalisation or requirement of oxygen supplementation, with the greatest benefit noted in patients at high-risk of progressing to severe COVID-19. The second part of the study remains ongoing and blinded. Therefore, results for the primary endpoint are forthcoming and will be presented at IDWeek. Disclosures Michael G. Ison, MD, MS, Celltrion, Inc. (Consultant) Jin Yong Kim, MD, MPH, Celltrion, Inc. (Scientific Research Study Investigator) Oana Sandulescu, MD, PhD, Algernon Pharmaceuticals (Scientific Research Study Investigator)Atea Pharmaceuticals (Scientific Research Study Investigator)Celltrion, Inc. (Scientific Research Study Investigator)Diffusion Pharmaceuticals (Scientific Research Study Investigator)Regeneron Pharmaceuticals (Scientific Research Study Investigator) Liliana-Lucia Preotescu, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Norma Erendira Rivera Martinez, MD, Celltrion, Inc. (Scientific Research Study Investigator) Marta Dobryanska, MD, Celltrion, Inc. (Scientific Research Study Investigator) Victoria Birlutiu, Assoc. Prof. M.D. Ph.D., Celltrion, Inc. (Scientific Research Study Investigator)Lucian Blaga University of Sibiu, Romania & Hasso Plattner Foundation (Research Grant or Support) Egidia Gabriela Miftode, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Natalia Gaibu, MD, Celltrion, Inc. (Scientific Research Study Investigator) Olga Adriana Caliman-Sturdza, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator)Stefan cel Mare University of Suceava, Romania (Research Grant or Support) Simin-Aysel Florescu, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Anca Streinu-Cercel, MD, PhD, Assoc.Prof. Infectious diseases, Algernon Pharmaceuticals (Scientific Research Study Investigator)Atea Pharmaceuticals (Scientific Research Study Investigator)Celltrion, Inc. (Scientific Research Study Investigator)Diffusion Pharmaceuticals (Scientific Research Study Investigator)Regeneron Pharmaceuticals (Scientific Research Study Investigator) Sang Joon Lee, n/a, Celltrion, Inc. (Employee) Sung Hyun Kim, n/a, Celltrion, Inc. (Employee) Il Sung Chang, n/a, Celltrion, Inc. (Employee) Yun Ju Bae, n/a, Celltrion, Inc. (Employee) Jee Hye Suh, n/a, Celltrion, Inc. (Employee) Mi Rim Kim, n/a, Celltrion, Inc. (Employee) Da Re Chung, n/a, Celltrion, Inc. (Employee) Sun Jung Kim, n/a, Celltrion, Inc. (Employee) Seul Gi Lee, n/a, Celltrion, Inc. (Employee) Ga Hee Park, n/a, Celltrion, Inc. (Employee) Joong Sik Eom, MD, PhD, Celltrion, Inc. (Consultant)

As global warming problem caused by greenhouse gas (GHG) emissions accelerates, many methods to remove carbon dioxide (CO2) have been proposed. In particular, CO2 decomposition has been developed for GHG emission reduction and CO2 upcycling. Our group previously reported on the results of efficient CO2 decomposition using SrFeO3-δ (perovskite-type metal oxide). According to the results of the isothermal test of SrFeO3-δ, reaction for a long time at high temperatures is necessary for effective CO2 decomposition, and this may lead to inefficient energy use. Therefore, in this study, Rh and Ru were impregnated as catalysts to SrFeO3-δ. As a result of CO2 decomposition using these catalysts, CO2 decomposition appeared at a low temperature of ∼200 °C. The maximum produced CO concentration was 3 times higher due to the spillover phenomenon of the precious metal catalysts. The cyclic tests showed catalyst stabilities of Rh- and Ru-SrFeO3-δ as well as the potential for continued and improved CO production. In additions, this study demonstrated that the decomposition of CO2 and the production of CO are performed by reverse Boudouard reactions as well as oxygen vacancies. It is expected that these results will contribute to GHG emission reduction.

Tumor necrosis factor-α has shown potent antitumor effects in preclinical and clinical studies. However, severe side effects at less than therapeutic doses have limited its systemic delivery, prompting the need for a new strategy for targeted delivery of the protein to tumors. Here, we report a fusion protein of mouse tumor necrosis factor (TNF)-α (mTNFα) and a cancer-targeting, high-affinity aptide, and investigate its therapeutic efficacy in tumor-bearing mice. A fusion protein consisting of mTNFα, a linker, and an aptide specific to extra domain B of fibronectin (APTEDB), designated mTNFα-APTEDB, was successfully produced by expression in Escherichia coli. mTNFα-APTEDB retained specificity and affinity for its target, EDB. In mice bearing EDB-overexpressing fibrosarcomas, mTNFα-APTEDB showed greater efficacy in inhibiting tumor growth than mTNFα alone or mTNFα linked to a non-relevant aptide, without causing an appreciable loss in body weight. Moreover, in vivo antitumor efficacy was further significan...

The authors make corrections, improvements and additions to their paper “Right primary and nilary rings and ideals” [J. Algebra 378 (2013) 133–152]. The following definition, results, proofs, and example have been corrected or revised: proof of Lemma 2.7, statement and proof of Theorem 2.8, the definition of irreducible ideal, statement and proof of Theorem 2.15, Example 2.17, Theorem 3.8, statement and proof of Corollary 3.9, statement of Theorem 3.15, and statement and proof of Corollary 3.16. The following items have been added: Definition A, Lemma B, and Example C.

A partial electrolyte (PE) treatment was performed on the Cu(In,Ga)Se 2 (CIGS) absorber layer of thin film solar cells to improve the quality of its interface with the cadmium sulfide (CdS) buffer layer. During the treatment, indium oxides and carbonates were removed and the CIGS surface was effectively doped by cadmium incorporation onto the surface. These effects were confirmed by scanning electron microscopy, x-ray and ultraviolet photoelectron spectroscopy. The surface cleaning and doping substantially improved the quality of the CdS/CIGS interface, which resulted in an order of magnitude lower dark current and the 3.0% enhanced power conversion efficiency of the PE-treated CIGS thin film solar cells, as compared with those of a conventional solar cell fabricated without PE-treatment.

Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress. BRNPs exerted potent antioxidant and anti-apoptotic activity in primary hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species (ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound protective effects against hepatocellular injury by reducing oxidative stress, pro-inflammatory cytokine production, and recruitment of neutrophils. They also preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our findings indicate that BRNP preconditioning provides a simple and safe approach that can be easily monitored in the blood like endogenous bilirubin, and could be a promising strategy to protect against IRI in a clinical setting.

In this study, ultrahigh-molecular-weight (MW) (>107Da) cationic polyacrylamides (C-PAMs), which are water-soluble polymers used in waste water treatment, were characterized using frit-inlet asymmetrical flow field-flow fractionation coupled with multi-angle light scattering and differential refractive detection. C-PAMs copolymerized with acryloxyethyltrimethyl ammonium chloride (DAC) were prepared by varying the feed amount of cationic monomer, polymerization method (solution vs. emulsion), and degree of branching. The MW of the copolymers prepared using emulsion polymerization (107-109Da) was generally larger than that of copolymers prepared using solution polymerization (4×107-108Da). When the amount of cationic monomer was increased from 10 to 55mol% in solution polymerization, hydrophobic contraction of the core induced formation of more compact C-PAMs. The copolymers prepared using emulsion polymerization formed highly aggregated or supercoil structures owing to increased intermolecular hydrophobic interaction when less cationic monomer was used. However, the MW decreased with increased cationic group content. In addition, C-PAMs larger than ∼108Da prepared using the emulsion method were separated by steric/hyperlayer elution mode while those in the 107-108Da range were analyzed in either normal or steric/hyperlayer mode depending on the decay patterns of field programming. Moreover, branched copolymers were found to be resolved with different elution modes under the same field decay pattern depending on the degree of branching: steric/hyperlayer for low-branching and normal for high-branching C-PAMs.

An ensemble statistical forecast scheme with a one-month lead is developed to predict year-to-year variations of Changma rainfall over the Korean peninsula. Spring sea surface temperature (SST) anomalies over the North Atlantic, the North Pacific and the tropical Pacific Ocean have been proposed as useful predictors in a previous study. Through a forward-stepwise regression method, four additional springtime predictors are selected: the northern Indian Ocean (NIO) SST, the North Atlantic SST change (NAC), the snow cover anomaly over the Eurasian continent (EUSC), and the western North Pacific outgoing longwave radiation anomaly (WNP (OLR)). Using these, three new prediction models are developed. A simple arithmetic ensemble mean produces much improved forecast skills compared to the original prediction model of Lee and Seo (2013). Skill scores measured by temporal correlation and MSSS (mean square error skill score) are improved by about 9% and 17%, respectively. The GMSS (Gerrity skill score) and hit rate based on a tercile prediction validation scheme are also enhanced by about 19% and 13%, respectively. The reversed NIO, reversed WNP (OLR), and reversed NAC are all related to the enhancement of a cyclonic circulation anomaly to the south or southwest of the Korean peninsula, which induces southeasterly moisture flux into the peninsula and increasing Changma precipitation. The EUSC predictor induces an enhancement of the Okhotsk Sea high downstream and thus strengthening of Changma front.

Background/Aims There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. Methods This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator`s judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/ disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. Results The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator`s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. Conclusion This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC. (J Neurogastroenterol Motil 2017;23:262-272)

In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.

As the coronavirus disease 2019 (COVID-19) outbreak is ongoing, the number of individuals to be tested for COVID-19 is rapidly increasing. For safe and efficient screening for COVID-19, drive-through (DT) screening centers have been designed and implemented in Korea. Herein, we present the overall concept, advantages, and limitations of the COVID-19 DT screening centers. The steps of the DT centers include registration, examination, specimen collection, and instructions. The entire service takes about 10 minutes for one testee without leaving his or her cars. Increased testing capacity over 100 tests per day and prevention of cross-infection between testees in the waiting space are the major advantages, while protection of staff from the outdoor atmosphere is challenging. It could be implemented in other countries to cope with the global COVID-19 outbreak and transformed according to their own situations., Graphical Abstract

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed., Graphical Abstract

Background and Objective: Since methomyl shows a highly significant toxicity, the clinical outcome of acute methomyl pesticide intoxication is extremely critical. Methomyl is a kind of carbamate poisons. Similar to intoxications with other carbamate insecticides, methomyl intoxication inhibits the activity of acetylcholinesterase, which is contained within synaptic junctions between neurons. Most of the methomyl intoxication cases present with symptoms of cholinergic excess, which provokes respiratory failure, cardiovascular failure, and/or cardiorespiratory failure. Methomyl poisoning in humans has not yet been fully evaluated and most studies have reported sporadic cases or series of intoxication. Methomyl poisoning remains a continuing challenge, because this difficult-to-treat clinical condition is frequently associated with significantly high mortality and morbidity. We evaluated the usefulness of extracorporeal membrane oxygenation in the treatment of methomyl intoxication. Methods: A systematic literature review was conducted using the PRISMA guidelines without language restriction. We searched for scientific publications via PubMed, Embase, Cochrane central register of controlled trial, Google Scholar, the KoreaMed, and the Research Information Sharing Service database. The goal of this study was to report on incidence, associated complications, and morbidity/mortality of methomyl poisoning, and to draw special attention to its management with extracorporeal membrane oxygenation. Results: Only 1 case of a child treated with extracorporeal membrane oxygenation for carbamate or organophosphate intoxication was identified in the literature. After carbamate or organophosphate intoxication, the patient suffered from severe complications including neurological deficits, renal insufficiency, and severe respiratory failure. This child was treated with continuous hemofiltration and extracorporeal membrane oxygenation, but expired after 38 days of extracorporeal membrane oxygenation. In case of our patient, he recovered from the methomyl intoxication after 7 days of VA-ECMO. Conclusions: With only a few exceptions, acute methomyl poisoning is potentially life-threatening and has high incidences of morbidity and mortality. Therefore, physicians should keep in mind the possibility of extracorporeal membrane oxygenation for the quick support of intoxication. Extracorporeal membrane oxygenation support might be an alternative to overcome the cholinergic excess, such as respiratory failure, cardiovascular failure, and/or cardiorespiratory failure, especially in the case of severe acute methomyl intoxication.

Background: We aimed to develop and distribute free artificial intelligence (AI) software for the automatic quantification of coronavirus disease 2019 (COVID-19) pneumonia on computed tomography (CT) images. Methods: We included 150 chest CT scans (17 CT scanners; five vendors) of 105 COVID-19 patients from 13 Korean and Chinese institutions. Two experienced radiologists semi-automatically drew lung opacities in every CT image, preparing 28,580 positive and negative CT slices to develop the 2D U-Net for segmenting pneumonia. The 2D U-Net was distributed as downloadable free software for local use on computers without data privacy concerns. External validation was performed using a Japanese single-institutional dataset and a public Italian dataset. Primary measures for the performance of the network were correlation coefficients for extent (%) and weight (g) of pneumonia. We surveyed user experiences. Findings: In the internal validation dataset, the intraclass correlation coefficients between the 2D U-Net and reference values for the extent and weight were 0·987 and 0·992, respectively. In the Japanese dataset, the Pearson correlation coefficients between the visual CT severity score and 2D U-Net outcomes were 0·906 and 0·916, respectively. In the Italian dataset, the intraclass correlation coefficients between the 2D U-Net and reference values for extent and weight were 0·921 and 0·970, respectively. The median satisfaction score was 9/10 and most respondents replied to use the software willingly. Interpretation: AI software for the automatic quantification of COVID-19 pneumonia on CT images was successfully developed and distributed freely worldwide. Funding Statement: There was no funding source for this study. Declaration of Interests: Sang Joon Park is the CEO of Medical IP. Gin Mo Goo has grants from Infinitt Healthcare, grants from Dongkook Lifescience, outside the submitted work. All the other authors have no potential conflicts of interest to disclose. Ethics Approval Statement: The institutional review board of the participating hospitals approved this retrospective study, and the requirement for patient consent was waived.

GOALS The study aimed to compare the level and characteristics of disease-related knowledge of patients with inflammatory bowel disease (IBD) between the West and the East using an international version of a questionnaire regarding knowledge of inflammatory bowel disease (IBD-KNOW). BACKGROUND The authors recently developed a new questionnaire regarding IBD-KNOW, which showed excellent test characteristics in Korea. STUDY The IBD-KNOW questionnaire was administered to 100 patients with IBD from tertiary referral hospitals in the United States and Korea. Scores were calculated and compared between US and Korean patients, and factors associated with high scores were analyzed. RESULTS A total of 196 (100 US and 96 Korean) patients with IBD completed the questionnaires. Analysis of the baseline characteristics revealed that male sex, smoking status, disease duration, history of IBD-related operations, family history of IBD, and use of corticosteroids or biologics were significantly different between US and Korean patients. The mean IBD-KNOW score was higher in US patients than in Korean patients (14.8 vs. 11.3; P

Background This study aimed to identify the incidence rate of episodes diagnosed with influenza and the effects of age-period-cohort (APC) in Koreans. Methods The 2009–2018 National Health Insurance Research Database was used for analysis. All time-related claims connected relatively short window period in 100 days. The case definition was defined by all codes diagnosed with J09, J10, and J11. Calculation of the incidence rate and APC analysis adjusted income levels by insurance type, metropolitan city was performed to identify the characteristics of episodes diagnosed with influenza. Results Incidence rate by age and cohort gradually increased since 2014. The incidence rate of males aged 0–4 years was 171.02 and that of females was 173.31 in 2015–2016 season. In males, 29.19 in 1963 cohort and 243.79 in 2013 cohort were confirmed as high incidence rates in 2017–2018 season. In the females, a high incidence was confirmed in 1953–1967 cohort and 1978–1987 cohort, and the incidence was 251.38 in 2013–2017 cohort. APC effects showed a high relative risk in the infants, the pandemic influenza season in 2010 (1/7/2009 to 30/6/2010) and the adults of 1978–1987 cohort. Conclusion Since 2014, influenza outbreaks have been increasing every year. The start year of free vaccination decreased the incidence in infants and adults over 65 years of age but the incidence increased from the following year. Because influenza can be primarily prevented by vaccination, reinforcement of vaccination in infants may reduce the disease burden in their parents, and also the risk of infection caused by family transmission. A new vaccination strategy is needed to reduce the incidence and burden of diseases caused by influenza infection., Graphical Abstract

The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy., Hair follicles (HFs) are sensitive to chemotherapy but recover from quiescent HF stem cells, although sometimes chemotherapy results in permanent loss. Here, Kim et al. establish a model of permanent chemotherapy-induced alopecia to uncover the underlying mechanisms depleting human HF stem cells.

Summary Background Antimicrobial stewardship programmes (ASPs) are suggested as a vital strategy to address antimicrobial resistance. Aim To examine the current status of ASPs in Korean hospitals, to identify problems and challenges for the implementation of proper ASPs, and to provide a reference for developing more effective ASP policies. Methods A questionnaire based on the ‘Seven Core Elements of Hospital Antibiotic Stewardship Programs’ from the US Centers for Disease Control and Prevention was developed, modified from the previous questionnaire on ASPs in Korea, 2015. ASP-participating physicians such as infectious disease specialists (IDSs), paediatric IDSs, and directors of infection control departments were targeted. Only one ASP-associated physician per hospital participated in the survey. Findings The survey response rate was 88.4% (84/95). The median number of medical personnel participating in ASPs was 3 (interquartile range (IQR): 1–5), most of whom were IDS (median: 2; IQR: 1–2). Only 6.0% (5/84) of hospitals had full-time workers for ASPs. Whereas restrictive measures for designated antimicrobials were widely implemented among Korean hospitals (88.1%, 74/84), the proportion of hospitals with interventions for inappropriate long-term antimicrobial use and a conversion strategy from parenteral to oral antimicrobial administration was only 9.5% (8/84) and 1.2% (1/84), respectively. Lack of time, personnel, and appropriate compensation was perceived as the major barrier to establishing an ASP in Korean hospitals. Conclusion ASPs in Korean hospitals were primarily carried out by one or two IDSs, and programmes mostly comprised restrictive measures for designated antimicrobials. National-level support to implement appropriate ASPs in Korean hospitals is necessary.

Nav1.2, a voltage-gated sodium channel subunit encoded by the Scn2a gene, has been implicated in various brain disorders, including epilepsy, autism spectrum disorder, intellectual disability, and schizophrenia. Nav1.2 is known to regulate the generation of action potentials in the axon initial segment and their propagation along axonal pathways. Nav1.2 also regulates synaptic integration and plasticity by promoting back-propagation of action potentials to dendrites, but whether Nav1.2 deletion in mice affects neuronal excitability, synaptic transmission, synaptic plasticity, and/or disease-related animal behaviors remains largely unclear. Here, we report that mice heterozygous for the Scn2a gene (Scn2a+/- mice) show decreased neuronal excitability and suppressed excitatory synaptic transmission in the presence of network activity in the hippocampus. In addition, Scn2a+/- mice show suppressed hippocampal long-term potentiation (LTP) in association with impaired spatial learning and memory, but show largely normal locomotor activity, anxiety-like behavior, social interaction, repetitive behavior, and whole-brain excitation. These results suggest that Nav1.2 regulates hippocampal neuronal excitability, excitatory synaptic drive, LTP, and spatial learning and memory in mice.

Background and aim Little is known whether routine prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is needed in patients with inflammatory bowel disease (IBD) on immunosuppression, especially in Asian populations. We, therefore, sought to investigate the incidence and risk factors of PJP in patients with IBD in Korea. Methods We investigated the incidence of PJP in patients with IBD and compared the characteristics of IBD patients with PJP episodes (IBD-PJP group) with those of matched controls (IBD-only group) using a large, well-characterized referral center-based cohort. Results Among the 6803 IBD patients (3171 with Crohn's disease and 3632 with ulcerative colitis) enrolled in the Asan IBD Registry between June 1989 and December 2016, six patients (0.09%) were diagnosed with PJP. During the 57 776.0 patient-years of follow-up (median 7.2 years per patient), the incidence of PJP was 10.4 cases per 100 000 person-years, and none of these patients had received PJP prophylaxis. In case-control analysis, the IBD-PJP group (n = 6) showed significantly higher C-reactive protein level at diagnosis of IBD (P = 0.006), as well as higher exposure to corticosteroids (P = 0.017), than did controls (n = 24). In addition, the IBD-PJP group showed higher rates of double (50% vs 12.5%) or triple (33.3% vs 4.2%) immunosuppression than did controls, although these are not statistically significant. Conclusions Although the incidence of PJP in Korean patients with IBD is low, careful monitoring is necessary for the early detection of PJP. In addition to the patients receiving double or triple immunosuppression, PJP prophylaxis should be considered especially in patients with severe disease activities requiring corticosteroids.

Background and Objective: Massive retroperitoneal hematoma caused by lumbar artery rupture is generally associated with trauma or retroperitoneal malignancy. However, despite recent advances in technologies and tools, spontaneous lumbar artery rupture is a very rare disease entity but remains a challenging problem because it is frequently associated with significantly high mortality and morbidity and is very difficult to make a correct diagnosis. Methods: We evaluated the databases of the PubMed, Embase, Cochrane Central Register of Controlled Trial, Google Scholar, the KoreaMed and the Research Information Sharing Service databases, and a detailed systematic review was performed by searching in PubMed. The initial search was performed on 3 February 2018 and a second search conducted in 29 January 2019. Results: A total of 10 case reports on massive hemoperitoneum caused by spontaneous lumbar artery rupture were identified. Of the 10 case reports involving 14 patients, eight were male and six were female under 62.71 ± 13.93. Of the 14 patients, 9 (64.3%) surviving with transcatheter arterial embolization, three (21.4%) died of multi-organ failure or hypovolemia, and two (14.3%) had no definite records on survival or death. Conclusions: A massive retroperitoneal hematoma caused by lumbar artery rupture should be considered in patients with late-onset shock accompanied by blunt abdominal/pelvic trauma. Furthermore, early detection and urgent embolization would prevent further complications and eliminate the need for surgical interventions.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious clinical disease entities characterized by inflammatory pulmonary edema, which lead to acute hypoxic respiratory failure through various etiologies. According to the studies to date, ALI/ARDS has been recognized as a form of multiorgan failure related to overactive immune response, and overproduction of proinflammatory cytokines released from activated inflammatory cells are considered to play a key role in the development of ALI. Glycyrrhizin (GL) is an extractive component derived from Glycyrrhiza glabra (licorice), which has recently been reported to have various pharmacological effects like anti-inflammatory, anti-tumor, hepato-protective, and anti-viral activities. Nevertheless, the therapeutic effect of GL in ALI is still unclear. The aim of this study was to investigate therapeutic effects of GL on lipopolysaccharide (LPS)-induced ALI in a mouse model and to elucidate explicable mechanisms involved. METHODS: A total of 36 BALB/c mice (6-week-old, 27.7±1.9-gram body weight) were randomly divided into 3 groups: the control group (normal saline was administered intravenously, n=10), the LPS group (LPS 50 mg/kg was intraperitoneally administered, n=13), and the LPS + GL group (GL was administered intravenously immediately and 12 hours after LPS injection, n=13). Mice were sacrificed after 24 hours, and bronchoalveolar lavage fluid (BALF) was collected for the estimation of protein content, inflammatory cell counts, proinflammatory cytokines, myeloperoxidase (MPO) activity, and expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). Then, the lungs were excised for molecular target, histopathological, and immunohistochemical examinations. RESULTS: Compared to the LPS group, GL significantly decreased protein content, inflammatory cell counts, tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-6, MPO activity, and expressions of COX-2, iNOS, and NF-κB in the LPS + GL group. GL attenuated migration and infiltration of inflammatory cells, showing a marked decrease in CD 11b-positive cells (26.77%±0.83% vs. 41.77%±0.81% vs. 23.23%±1.92%, P

Background and Objective: Massive retroperitoneal hematoma caused by lumbar artery rupture is generally associated with trauma or retroperitoneal malignancy. However, despite recent advances in technologies and tools, spontaneous lumbar artery rupture is a very rare disease entity but remains a challenging problem because it is frequently associated with significantly high mortality and morbidity and is very difficult to make a correct diagnosis. Methods: We evaluated the databases of the PubMed, Embase, Cochrane Central Register of Controlled Trial, Google Scholar, the KoreaMed and the Research Information Sharing Service databases, and a detailed systematic review was performed by searching in PubMed. The initial search was performed on 3 February 2018 and a second search conducted in 29 January 2019. Results: A total of 10 case reports on massive hemoperitoneum caused by spontaneous lumbar artery rupture were identified. Of the 10 case reports involving 14 patients, eight were male and six were female under 62.71 ± 13.93. Of the 14 patients, 9 (64.3%) surviving with transcatheter arterial embolization, three (21.4%) died of multi-organ failure or hypovolemia, and two (14.3%) had no definite records on survival or death. Conclusions: A massive retroperitoneal hematoma caused by lumbar artery rupture should be considered in patients with late-onset shock accompanied by blunt abdominal/pelvic trauma. Furthermore, early detection and urgent embolization would prevent further complications and eliminate the need for surgical interventions. How to cite this:Kim JY, Lee SA, Hwang JJ, Park JB, Park SW, Kim YH, et al. Spontaneous lumbar artery rupture and massive retroperitoneal hematoma, successfully treated with arteriographic embolization. Pak J Med Sci. 2019;35(2):569-574. doi: https://doi.org/10.12669/pjms.35.2.639 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This study investigated the flexural behavior of concrete-encased steel angle girders (PSRC girders). Inside the concrete section, high-strength steel angles (Fy = 605 MPa) with unequal legs were used as longitudinal reinforcement, and diagonal and vertical members were bolt-connected to the longitudinal angles as transverse ties. Flexural tests were performed for three PSRC girder specimens with different reinforcement details. The tests showed that the PSRC girders all developed the peak loads exceeding the nominal strengths; however, the ductility was limited as rupture occurred near bolt holes in the longitudinal angles. Overall, the concrete damage and cracking of the PSRC girders were comparable to those in conventional reinforced concrete beams, and cover spalling and bond deterioration along the longitudinal angles were not severe. The strength, stiffness, and ductility estimated in accordance with current design codes were compared with the test results. Given the investigation results, the application and design considerations of PSRC girders were discussed.

Artificial intelligence technologies and robot vision systems are core technologies in smart factories. Currently, there is scholarly interest in automatic data feature extraction in smart factories using deep learning networks. However, sufficient training data are required to train these networks. In addition, barely perceptible noise can affect classification accuracy. Therefore, to increase the amount of training data and achieve robustness against noise attacks, a data augmentation method implemented using the adaptive inverse peak signal-to-noise ratio was developed in this study to consider the influence of the color characteristics of the training images. This method was used to automatically determine the optimal perturbation range of the color perturbation method for generating images using weights based on the characteristics of the training images. The experimental results showed that the proposed method could generate new training images from original images, classify noisy images with greater accuracy, and generally improve the classification accuracy. This demonstrates that the proposed method is effective and robust to noise, even when the training data are deficient.

The kinetic ballooning mode destabilized by the ion magnetic curvature drift resonance in the 2nd ballooning stability regime is shown to be a plausible candidate for the low-k broadband fluctuation recently observed in the wide-pedestal quiescent-H (QH) mode of DIII-D. With its intrinsic real frequency approaching very closely to the ion pressure diamagnetic frequency in the pedestal-like condition with a steep gradient, this mode can be nearly free from the first-order ExB flow shear effect driven by the ion pressure gradient. As a result, it can be sensitive to the next-order one by toroidal rotation, with the possible strong excitation in the low toroidal rotation limit. The frequency in the lab frame and the peak wavenumber spectrum of the mode appear to be in the range similar to those of the observed low-k fluctuation.

Background and Objective Lasers have been successfully used for decades to remove dark hair. However, laser removal of nonpigmented hair is challenging due to the lack of chromophores. The aim of this study was to use photodynamic therapy (PDT) to remove nonpigmented hair. Study Design/Material and Methods We compared the efficacy of permanent hair reduction in white BALB/c and black C57BL/6 mice treated with PDT or an 800-nm diode laser. We collected skin biopsy specimens and investigated post-PDT histologic changes and molecular changes. Results We observed keratin 15 staining in the bulge area and alkaline phosphatase staining in the dermal papilla following PDT. We observed a temporary, catagen-like transformation in nonpigmented hair follicles after PDT. We observed apoptotic cells in the hair matrix after PDT. Irradiation with an 800-nm diode laser did not achieve nonpigmented hair removal. Multiple PDT sessions achieved permanent reduction of nonpigmented hair. Interestingly, removal of black hair using PDT was less efficient. Conclusion Our results suggest that PDT can damage the nonpigmented hair matrix, but not stem cells or dermal papillae. Repeated PDT may impair the hair-regeneration capacity via a bystander effect on bulge stem cells or dermal papillae. In this study, we found it was possible to remove nonpigmented hair using PDT. Lasers Surg. Med. 48:748–762, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: Oligopeptides; 1H iterative Full Spin Analysis (HiFSA); Ecumicin; Computational Iteration; Structure elucidation

While natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (HP)TLC-bioautography-MS/NMR, which combines cutting-edge microbiological, chromatographic, and spectrometric technologies, was developed to accelerate anti-tuberculosis (TB) drug discovery from natural sources by acquiring structural information at a very early stage of the isolation process. Using the avirulent, bioluminescent Mtb strain mc27000 luxABCDE, three variations of bioautography were evaluated and optimized for sensitivity in detecting anti-TB agents, including established clinical agents and new leads with novel mechanisms of action. Several exemplary applications of this approach to microbial extracts demonstrate its potential as a routine method in anti-TB drug discovery from natural sources.

A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

Fast and effective protein digestion is a vital process for mass spectrometry (MS) based protein analysis. This study introduces a porous polymer membrane enzyme reactor (PPMER) coupled to nanoflow liquid chromatography-tandem MS (nLC-ESI-MS/MS) for on-line digestion and analysis of proteins. Poly (styrene-co-maleic anhydride) (PS-co-MAn) was fabricated by the breath figure method to make a porous polymer membrane in which the MAn group was covalently bound to enzyme. Based on this strategy, microscale PPMER (μPPMER) was constructed for on-line connection with the nLC-ESI-MS/MS system. Its capability for enzymatic digestion with bovine serum albumin (BSA) was evaluated with varied digestion periods. The on-line proteolysis of BSA and subsequent analysis with μPPMER-nLC-ESI-MS/MS revealed that peptide sequence coverage increased from 10.3% (digestion time 10 min) to 89.1% (digestion time 30 min). μPPMER can efficiently digest proteins due to the microscopic confinement effect, showing its potential application in fast protein identification and protease immobilization. Applications of on-line digestion using μPPMER with human plasma and urinary proteome samples showed that the developed on-line method yielded equivalent or better performance in protein coverage and identified more membrane proteins than the in-solution method. This may be due to easy accommodation of hydrophobic membrane proteins within membrane pores.

Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium–nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg−1, higher than that of conventional tubular sodium–nickel chloride batteries (280 °C), is obtained for planar sodium–nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium–nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs., Sodium metal halide batteries are attractive technologies for stationary electrical energy storage. Here, the authors report that planar sodium-nickel chloride batteries operated at an intermediate temperature of 190 °C display larger energy densities than tubular batteries operated at higher temperatures.

In the case of structural analysis for building structures, the super-structure and the sub-structure are analyzed by using separate structural models in the field because of time saving, facile result interpretation and easy analysis of dynamic behavior. However this separate structural model violated the compatibility condition of structural analysis and it can not consider the interaction of superand sub- structures. In the present study, the analysis results of this separate model were compared to those of the unified model of super- and sub- structures which can consider the interaction of super- and sub- structures and reflect the realistic boundary conditions. According to the comparison results, the the analysis model using separate models can underestimate the member force and deflection of structural members in the super-structures and overestimate the deflection and member force of sub-structures. Therefore, in the case of high-rise buildings, irregular shaped buildings, buildings which are expected to be affected by large differential settlement and remodeling buildings, the unified structural model for super- and sub- structures was recommended for structural analysis instead of the separate structural model.

The peninsular effect is a geographical phenomenon that explains patterns of species richness. Given that spatial variation in species richness along a peninsular may be driven by multiple processes, we aimed to identify the sources of latitudinal patterns in passerine species richness and test hypotheses regarding (1) recent deterministic processes (climate, primary productivity, forest area, and habitat diversity), (2) anthropogenic processes (habitat fragmentation), and (3) stochastic processes (migration influence) in the Korean peninsula. We used the distribution data of 147 passerine species from 2006 to 2012. Single regression between passerine species richness and latitude supported the existence of the peninsular effect. Mean temperature increased with decreasing latitude, as did habitat diversity but leaf area index and forest area decline. However, mean temperature and forest area only influenced passerine species richness. Although habitat diversity influenced passerine species richness, it was counter to the expectations associated with peninsular effect. The number of habitat patches decreased as latitude increased but it had no effect on passerine species richness. Ratio of migrant species richness showed no significant relationship with leaf area index, forest area, and habitat diversity. However, the ratio of migrant species richness increased with decreasing mean temperature and that contributed to the increase in passerine species. Overall, our finding indicate that the observed species richness pattern in peninsulas with the tip pointing south (in the northern hemisphere) counter to the global latitudinal gradient. These results were caused by the peninsular effect associated with complex mechanism that interact with climate, habitat area, and migrant species inflow.

In the Original publication of the article, the grant number was incorrectly published in the acknowledge section.

A low-noise, wide-bandwidth DNA readout instrument for nanopore applications is presented. Owing to hardware simplicity and reliability, a resistive-feedback transimpedance amplifier (rf-TIA) is adopted as the headstage for the readout instrument. However, to achieve a high gain and low input noise, its high feedback resistance induces a high parasitic capacitance, thus significantly limiting the 3 dB bandwidth. To drastically reduce the parasitic capacitance and widen the bandwidth, a novel rf-TIA architecture is fabricated that utilises a split-resistor technique for the high feedback resistor. This is demonstrated in a benchtop test employing an α-haemolysin nanopore.

We describe a novel approach for angle-resolved spectral reflectometry using a digital light processing (DLP) projector. Here, the DLP generates ring patterned images which are projected on the back focal plane of an objective lens. This way, the proposed method quickly changes the angle of incidence with ease based on the relation between the radius of the back focal plane and the angle of incidence. As a result, a detector captures the intensity of the image plane based on the angular and spectral axis. As the proposed method detects the interesting spot of a sample image, it can easily locate the measurement spot with viewing the full field of view, and the spot size is reduced by adopting the fiber. This method is verified by comparing the measurement output of the thin-film samples with a commercial ellipsometer. The result shows that our the proposed method enables the high accuracy of the thin-film inspection.

Objective: In 2020, the coronavirus disease 2019 (COVID-19) respiratory infection is spreading in Korea. In order to prevent the spread of an infectious disease, infected people must be quickly identified and isolated, and contact with the infected must be blocked early. This study attempted to verify the intervention effects on the spread of an infectious disease by using these measures in a mathematical model. Methods: We used the susceptible-infectious-recovery (SIR) model for a virtual population group connected by a special structured network. In the model, the infected state (I) was divided into I in which the infection is undetected and Ix in which the infection is detected. The probability of transitioning from an I state to Ix can be viewed as the rate at which an infected person is found. We assumed that only those connected to each other in the network can cause infection. In addition, this study attempted to evaluate the effects of isolation by temporarily removing the connection among these people. Results: In Scenario 1, only the infected are isolated; in Scenario 2, those who are connected to an infected person and are also found to be infected are isolated as well. In Scenario 3, everyone connected to an infected person are isolated. In Scenario 3, it was possible to effectively suppress the infectious disease even with a relatively slow rate of diagnosis and relatively high infection rate. Conclusion: During the epidemic, quick identification of the infected is helpful. In addition, it was possible to quantitatively show through a simulation evaluation that the management of infected individuals as well as those who are connected greatly helped to suppress the spread of infectious diseases.

Cytoplasmic FMR1-interacting protein 2 (CYFIP2) is a key component of the WAVE regulatory complex (WRC) which regulates actin polymerization and branching in diverse cellular compartments. Recent whole exome sequencing studies identified de novo hotspot variants in CYFIP2 from patients with early-onset epileptic encephalopathy and microcephaly, suggesting that CYFIP2 may have some functions in embryonic brain development. Although perinatal lethality of Cyfip2-null (Cyfip2−/−) mice was reported, the exact developmental time point and cause of lethality, and whether Cyfip2−/− embryonic mice have brain abnormalities remain unknown. We found that endogenous Cyfip2 is mainly expressed in the brain, spinal cord, and thymus of mice at late embryonic stages. Cyfip2−/− embryos did not show lethality at embryonic day 18.5 (E18.5), but their body size was smaller than that of wild-type (WT) or Cyfip2+/− littermates. Meanwhile, at postnatal day 0, all identified Cyfip2−/− mice were found dead, suggesting early postnatal lethality of the mice. Nevertheless, the brain size and cortical cytoarchitecture were comparable among WT, Cyfip2+/−, and Cyfip2−/− mice at E18.5. Using RNA-sequencing analyses, we identified 98 and 72 differentially expressed genes (DEGs) from the E18.5 cortex of Cyfip2+/− and Cyfip2−/− mice, respectively. Further bioinformatic analyses suggested that extracellular matrix (ECM)-related gene expression changes in Cyfip2−/− embryonic cortex. Together, our results suggest that CYFIP2 is critical for embryonic body growth and for early postnatal survival, and that loss of its expression leads to ECM-related gene expression changes in the embryonic cortex without severe gross morphological defects.

Quantitative opacity mass and three-dimensional opacity volume on CT were quantifiable metrics affecting the visibility of COVID-19–related opacities on chest radiographs.

Recent analyses [for example, see the paper by G.M. Staebler et al., Phys. Plasmas 056113 (2018)] indicate that in DIII-D high poloidal-beta discharges turbulent transport, particularly for ions, are governed by the electromagnetic kinetic ballooning mode (KBM) in most radial region, including the outer core between internal and external transport barriers (ITB and ETB). Considering that in the usual L- or H-mode plasmas turbulent transport is widely believed to be dominated by the electrostatic drift-type modes, such as the ion temperature gradient (ITG) or trapped electron mode (TEM), a modeling study is presented about how this transition of dominant mode can occur. In the ITB region, where there already exist several theoretical models, the focus is put on clarifying the relative role between the Shafranov-shift and linear electromagnetic effects. While these two can play an important role for the transition or ITB formation by stabilizing the electrostatic drift-type modes, a significant difference is found in that the former mainly works on the TEM, while the latter on the ITG. In contrast to the ITB region, in the outer core between ITB and ETB the transition appears to be more relevant to the destabilization of KBM itself, rather than the stabilization of electrostatic modes. A jump of edge plasma beta through pedestal formation is shown to play the critical role in this destabilization by making the KBM threshold temperature gradient smaller than the ITG/TEM one, thus allowing an earlier excitation of KBM when background temperature gradients increase by external heating.