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Background: Liraglutide, a drug used for the management of obesity, has many known side effects. In this study, we developed a predictive model for the occurrence of liraglutide-related side effects using data from electronic medical records (EMRs).Methods: This study included 237 patients from Seoul St. Mary's Hospital and Eunpyeong St. Mary's Hospital who were prescribed liraglutide. An endocrinologist obtained medical data through an EMR chart review. Model performance was evaluated using the mean of the area under the receiver operating characteristic curve (AUROC) with a 95% confidence interval (CI).Results: A predictive model was developed for patients who were prescribed liraglutide. However, 37.1% to 75.5% of many variables were missing, and the AUROC of the developed predictive model was 0.630 (95% CI, 0.551–0.708). Patients who had previously taken antiobesity medication had significantly fewer side effects than those without previous antiobesity medication use (20.7% vs. 41.4%, P

Supplementary Figure 4 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

Supplementary Figure 1 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

Supplementary Table 1 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

DNA damage stabilizes the p53 tumor suppressor protein that determines the cell fate by either cell cycle arrest or cell death induction. Noxa, the BH3-only Bcl-2 family protein, was shown to be a key player in p53-induced cell death through the mitochondrial dysfunction; however, the molecular mechanism by which Noxa induces the mitochondrial dysfunction to cause cell death in response to genotoxic agents is largely unknown. Here, we show that the mitochondrial-targeting domain (MTD) of Noxa is a prodeath domain. Peptide containing MTD causes massive necrosis in vitro through cytosolic calcium increase; it is released from the mitochondria by opening the mitochondrial permeability transition pore. MTD peptide–induced cell death can be inhibited by calcium chelator BAPTA-AM. Moreover, MTD peptide shows the potent tumor-killing activities in mice by joining with tumor-homing motifs. [Cancer Res 2009;69(21):8356–65]

Supplementary Figure 3 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

Supplementary Methods, Figure Legends 1-4 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

Supplementary Figure 2 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

Background Atelectasis can occur in many clinical practices. One way to prevent this complication is through the alveolar recruitment maneuver (ARM). However, hemodynamic compromise can accompany ARM. This study aims to predict ARM-induced hypotension using a non-invasive method. Methods 94 American Society of Anesthesiologists physical status I–II patients aged 19 to 75 with scheduled spinal surgery were enrolled. After anesthesia, we performed a stepwise ARM. Data on perfusion index, mean arterial pressure, heart rate, pleth variability index, cardiac index, and stroke volume variation was collected before induction of anesthesia (T0), just before ARM (T1), at the start of ARM (T2), 0.5 min (T3), 1 min (T4), 1.5 min (T5, end of ARM), and 2 min after the beginning of ARM (T6). Hypotension was defined as when the mean arterial pressure at T5 decreased by 20% or more compared to the baseline. The primary endpoint is that the perfusion index measuring before induction of anesthesia, which reflects the patients’ own vascular tone, was correlated with hypotension during ARM. Results Seventy-five patients (79.8%) patients developed hypotension during ARM. The pre-induction persufion index (Pi) (95% confidence interval) was 1.7(1.4–3.1) in the non-hypotension group and 3.4(2.4–3.9) in the hypotension group. (p p p = 0.004), and the threshold value of the Pi was 2.4. Conclusion A higher perfusion index value measuring before induction of anesthesia can be used to predict the development of hypotension during ARM. Prophylactic management of the following hypotension during ARM could be considered in high baseline Pi patients.

To identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseudovirus assay and an alpha test for rapid identification of potential antiviral compounds and their mechanism of action, which can lead to the accelerated development of therapeutics against newly emerging viral infections.

In this study, a high-photoresponsivity self-powered deep ultraviolet (DUV) photodetector based on an Ag

Self-powered deep-ultraviolet photodetectors have received considerable attention in recent years because of their efficiency, reliability, and various applications in civilian and military fields. Herein, a Ag/Ag

Grape ripe rot is a fungal disease, which is almost inextinguishable particularly before and after harvest in most vineyards. The management of this disease largely depends on the breeding of resistant varieties. Thus, the search for resistant varieties should parallel the molecular analysis of the markers associated with disease resistance. Here, we tested the leaf inoculation assay of Colletotrichum acutatum and C. gloeosporioides by inoculating them into 350 grapevine varieties. As a result of the phenotypes common to both species, 119 varieties (34%) were classified as resistant. Consequently, we discovered the locus with nucleotide-binding sites and carboxyterminal leucine-rich repeat regions (NBS-LRR) associated with grape ripe rot resistance through genotyping-by-sequencing and genome-wide association study. Ultimately, we identified the Vitis vinifera Colletotrichum resistance protein (VvCRP) markers from chromosome 3, which belongs to the CC-NBS-LRR type, as disease-resistant proteins. These markers were verified as the melting peak, and their chromatograms of nucleotide sequences were visualized in each single nucleotide polymorphism (SNP) loci. All the SNP markers differentiated successfully the resistant from the susceptible cultivars. Interestingly, we also found that a resistant cultivar named Bailey Alicante A has a heterozygous genotype, substantiating its potential usefulness for crops such as grapevine with many hybrids. Altogether, our results indicate that VvCRP markers can be utilized to distinguish grape ripe rot-resistant cultivars, particularly in crossbreeding populations.

Background A clinical decision support system (CDSS) is recognized as a technology that enhances clinical efficacy and safety. However, its full potential has not been realized, mainly due to clinical data standards and noninteroperable platforms. Objective In this paper, we introduce the common data model–based intelligent algorithm network environment (CANE) platform that supports the implementation and deployment of a CDSS. Methods CDSS reasoning engines, usually represented as R or Python objects, are deployed into the CANE platform and converted into C# objects. When a clinician requests CANE-based decision support in the electronic health record (EHR) system, patients’ information is transformed into Health Level 7 Fast Healthcare Interoperability Resources (FHIR) format and transmitted to the CANE server inside the hospital firewall. Upon receiving the necessary data, the CANE system’s modules perform the following tasks: (1) the preprocessing module converts the FHIRs into the input data required by the specific reasoning engine, (2) the reasoning engine module operates the target algorithms, (3) the integration module communicates with the other institutions’ CANE systems to request and transmit a summary report to aid in decision support, and (4) creates a user interface by integrating the summary report and the results calculated by the reasoning engine. Results We developed a CANE system such that any algorithm implemented in the system can be directly called through the RESTful application programming interface when it is integrated with an EHR system. Eight algorithms were developed and deployed in the CANE system. Using a knowledge-based algorithm, physicians can screen patients who are prone to sepsis and obtain treatment guides for patients with sepsis with the CANE system. Further, using a nonknowledge-based algorithm, the CANE system supports emergency physicians’ clinical decisions about optimum resource allocation by predicting a patient’s acuity and prognosis during triage. Conclusions We successfully developed a common data model–based platform that adheres to medical informatics standards and could aid artificial intelligence model deployment using R or Python.

BACKGROUND In adults, the use of lower oxygen concentration during induction is associated with less atelectasis formation without an increase in incidence of hypoxia. However, it is unknown whether this remains true in the pediatric patients. METHODS Fifty-four pediatric patients who were scheduled to undergo elective lower abdominal surgery were randomized to one of three oxygenation groups: 100%, 80%, or 60% oxygen (in air). During anesthesia induction, patients were ventilated with sevoflurane in 100%, 80%, or 60% oxygen. Endotracheal intubation and mechanical ventilation were performed. Atelectasis was diagnosed using LUS, which was performed after anesthetic induction and at the end of surgery. RESULTS We assessed atelectasis after anesthetic induction and at the end of surgery. After anesthetic induction, the number of atelectatic lung regions was significantly different among the three groups (median [IQR], 2.0 [1.0-2.5], 2.0 [1.0-2.8], and 3.0 [2.0-3.0] in the 60%, 80%, and 100% oxygen groups, p = .033) and between the 60% and 100% groups (p = .015), but not between 80% and 100% groups (p = .074). However, no differences in the number of atelectatic lung regions were found among the three groups at the end of surgery (2.0 [1.3-3.8], 3.0 [1.8-3.0], and 4.0 [2.0-4.0] in the 60%, 80%, and 100% oxygen groups; p = .169). CONCLUSION Lower oxygen concentration during anesthetic induction is associated with less atelectasis formation immediately after anesthetic induction in children. In addition, applying 80% oxygen instead of 100% oxygen is not enough to prevent atelectasis formation, and 60% oxygen should be applied to prevent atelectasis. However, this effect does not last until the end of surgery.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years.In this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration.The RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6-99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99-1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86-1.22] to 1.36 [95%CI: 1.07-1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone.RZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.

Background. Acute kidney injury (AKI) is one of the common complications after living donor liver transplantation (LDLT) and is associated with increased mortality and morbidity. The prognostic nutritional index (PNI) has been used as a predictive model for postoperative complications. Here, we create a new predictive model based on the PNI and compared its predictive accuracy to other models in patients who underwent LDLT. Material and Methods: The data from 423 patients were collected retrospectively. The patients were dichotomized into the non-AKI and the AKI groups. Multivariate adjustment for significant postoperative variables based on univariate analysis was performed. A new predictive model was created using the results from logistic regression analysis, dubbed the modified-PNI model (mPNI). The area under the receiver operating characteristic curve (AUC) was generated to determine the diagnostic accuracy and cutoff value of individual models. The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to investigate diagnostic improvement by the mPNI. Results: Fifty-four patients (12.7 %) were diagnosed with AKI within 1-week after LDLT. The mPNI had the highest predictive accuracy (AUC = 0.823). The model of end-stage liver disease (MELD) scores and PNI were 0.793 and 0.749, respectively, and the INR and serum bilirubin were 0.705 and 0.637, respectively. The differences in the AUCs were statistically significant among the mPNI, PNI, INR, and serum bilirubin. The cutoff value for mPNI was 8.7. The NRI was 10.4% and the IDI was 3.3%. Conclusions: The mPNI predicted AKI within 1-week better than other scoring systems in patients who underwent LDLT. The recommended cutoff value of mPNI is 8.7.

In this study, a high-photoresponsivity self-powered deep ultraviolet (DUV) photodetector based on an Ag2O/β-Ga2O3 heterojunction was fabricated by depositing a p-type Ag2O thin film onto an n-type β-Ga2O3 layer. The device characteristics after post-annealing at temperatures ranging from 0 to 400 °C were investigated. Our DUV devices exhibited typical rectification characteristics. At a post-annealing temperature of 300 °C, the as-fabricated device had a low leakage current of 4.24 × 10−11 A, ideality factor of 2.08, and a barrier height of 1.12 eV. Moreover, a high photo-responsivity of 12.87 mA/W was obtained at a 100 μW/cm2 light intensity at a 254 nm wavelength at zero bias voltage, the detectivity was 2.70 × 1011 Jones, and the rise and fall time were 29.76, 46.73 ms, respectively. Based on these results, the Ag2O/β-Ga2O3 heterojunction photodetector operates without an externally applied voltage and has high responsivity, which will help in the performance improvement of ultraviolet sensing systems.

Positive end-expiratory pressure (PEEP) following alveolar recruitment manoeuvre (RM) can effectively prevent anaesthesia-induced atelectasis in children. We aimed to evaluate the individual effect of PEEP following RM on atelectasis at the end of laparoscopic surgery in infants and small children.Children undergoing laparoscopic inguinal hernia repair aged 5 weeks to 2 years were randomly allocated to either the PEEP or control group. A progressive RM was performed after intubation in all cases. The PEEP group received PEEP of 5 cmHOverall, 432 ultrasonographic images were acquired from 36 children. At the end of surgery, the number of atelectatic regions (median [interquartile range]) was significantly lower in the PEEP group compared to the control group (2.0 [1.0-3.0] versus 4.0 [3.0-4.0] out of 12 regions, respectively; p = 0.02). While no difference was observed between the number of atelectatic regions after induction and at the end of surgery in the control group (p = 0.30), a decrease was observed in the PEEP group (3.0 [2.0-4.0] to 2.0 [1.0-3.0], respectively; p = 0.02).RM followed by a PEEP of 5 cmH

Postural change from a steep Trendelenburg position to a supine position (T-off) during robot-assisted laparoscopic prostatectomy (RALP) induces a considerable abrupt decrease in the mean arterial pressure (MAP). We investigated the variables for predicting postural hypotension induced by T-off using esophageal Doppler monitoring (EDM). One hundred and twenty-five patients undergoing RALP were enrolled. Data on the MAP, heart rate, stroke volume index (SVI), cardiac index, peak velocity, corrected flow time, stroke volume variation, pulse pressure variation, arterial elastance (Ea), and dynamic arterial elastance were collected before T-off and at 1, 3, 5, 7, and 10 min after T-off using EDM. MAP P P P 2, and ≤ 1.08 mmHg/mL, respectively. If patients have MAP 2 or Ea ≤ 1.08 mmHg/mL before postural change from T-off during RALP, prompt management for ensuing hypotension should be considered.Trial registration: NCT03882697 (ClinicalTrial.gov, March 20, 2019).

Zika virus (ZIKV) infection in both infants and adults is associated with neurological complications including, but not limited to, microcephaly and Guillain-Barre syndrome. Antibody therapy can be effective against virus infection. We isolated ZIKV envelope domain III-specific neutralizing antibodies (nAbs) from two convalescent patients with ZIKV infection. One antibody, 2F-8, exhibited potent in vitro neutralizing activity against Asian and American strains of ZIKV. To prevent FcγR-mediated antibody-dependent enhancement, we prepared IgG1 with LALA variation. A single dose of 2F–8 in the context of IgG1 or IgG1-LALA prior to or post lethal ZIKV challenge conferred complete protection in mice.

BACKGROUND Patient safety in the intensive care unit (ICU) is one of the most critical issues, and unplanned extubation (UE) is considered the most adverse event for patient safety. Prevention and early detection of such an event is an essential but difficult component of quality care. OBJECTIVE This study aimed to develop and validate prediction models for UE in ICU patients using machine learning. METHODS This study was conducted in an academic tertiary hospital in Seoul, Republic of Korea. The hospital had approximately 2000 inpatient beds and 120 ICU beds. As of January 2019, the hospital had approximately 9000 outpatients on a daily basis. The number of annual ICU admissions was approximately 10,000. We conducted a retrospective study between January 1, 2010, and December 31, 2018. A total of 6914 extubation cases were included. We developed a UE prediction model using machine learning algorithms, which included random forest (RF), logistic regression (LR), artificial neural network (ANN), and support vector machine (SVM). For evaluating the model’s performance, we used the area under the receiver operating characteristic curve (AUROC). The sensitivity, specificity, positive predictive value, negative predictive value, and F1 score were also determined for each model. For performance evaluation, we also used a calibration curve, the Brier score, and the integrated calibration index (ICI) to compare different models. The potential clinical usefulness of the best model at the best threshold was assessed through a net benefit approach using a decision curve. RESULTS Among the 6914 extubation cases, 248 underwent UE. In the UE group, there were more males than females, higher use of physical restraints, and fewer surgeries. The incidence of UE was higher during the night shift as compared to the planned extubation group. The rate of reintubation within 24 hours and hospital mortality were higher in the UE group. The UE prediction algorithm was developed, and the AUROC for RF was 0.787, for LR was 0.762, for ANN was 0.763, and for SVM was 0.740. CONCLUSIONS We successfully developed and validated machine learning–based prediction models to predict UE in ICU patients using electronic health record data. The best AUROC was 0.787 and the sensitivity was 0.949, which was obtained using the RF algorithm. The RF model was well-calibrated, and the Brier score and ICI were 0.129 and 0.048, respectively. The proposed prediction model uses widely available variables to limit the additional workload on the clinician. Further, this evaluation suggests that the model holds potential for clinical usefulness.

The massive epidemic of Ebola virus disease (EVD) in West Africa, followed in recent months by two outbreaks in the Democratic Republic of the Congo, underline the importance of this severe disease. Because Ebola virus (EBOV) must be manipulated under biosafety level 4 (BSL4) containment, the discovery and development of virus-specific therapies have been hampered. Recently, a transient transfection-based transcription- and replication competent virus-like particle (trVLP) system was described, enabling modeling of the entire EBOV life cycle under BSL2 conditions. Using this system, we optimized the condition for bulk co-transfection of multiple plasmids, developed a luciferase reporter-based assay in 384-well microtiter plates, and performed a high-throughput screening (HTS) campaign of an 8,354-compound collection consisting of U.S. Food & Drug Administration (FDA) -approved drugs, bioactives, kinase inhibitors, and natural products in duplicates. The HTS achieved a good signal-to-background ratio with a low percent coefficient of variation resulting in Z’ = 0.7, and data points were reproducible with R2 = 0.89, indicative of a robust assay. After applying stringent hit selection criteria of ≥70% EBOV trVLP inhibition and ≥70% cell viability, 381 hits were selected targeting early, entry, and replication steps and 49 hits targeting late, maturation, and secretion steps in the viral life cycle. Of the total 430 hits, 220 were confirmed by dose-response analysis in the primary HTS assay. They were subsequently triaged by time-of-addition assays, then clustered and ranked according to their chemical structures, biological functions, therapeutic index, and maximum inhibition. Several novel drugs have been identified to very efficiently inhibit EBOV. Interestingly, most showed pharmacological activity in treatments for central nervous system-related diseases. We developed and screened an HTS assay using the novel EBOV trVLP system. Newly identified inhibitors are useful tools to study the poorly understood EBOV life cycle. In addition, they also provide opportunities to either repurpose FDA-approved drugs or develop novel viral interventions to combat EVD.

Purpose : To assess the change of binocular visual function and visual acuity in monovision surgery patients. Methods : The subjects were 58(49.57 ± 3.27 years) monovision patients who wear glasses and contact lens before monovision surgery. 100% and 10% contrast visual acuity, near stereoacuity, distance and near convergence fused amplitude, amplitude of accommodation were measured and visual satisfaction in the real life after surgery was evaluated using a Questionnaire. All measurements were conducted before and after 1, 3 and 6 months of surgery. The pre-operative measurements were performed with glasses or contact lenses on, and post-operative measurements were conducted in the naked eye. All measurements among groups were statistically analyzed with the SPSS 21.0. Results : Among 58 subjects, 5 subjects (10 eyes) were hyperopia, 53 subjects (106 eyes) were myopia. Binocular distance and near contrast visual acuity was decreased after surgery, especially the 10 % contrast visual acuity under mesopic condition was decreased and there was no difference according to the postoperative period. In the questionnaire survey, satisfaction of distance and near vision after surgery was getting better, and night glare was worsen compare to pre-operation, however, general satisfaction was high after surgery. The near stereoacuity and distance convergence fused amplitude were decreased, and no changes in near sensory suppression and near convergence fused amplitude, and the amplitude of accommodation was increased in binocular and non-dominant eye after monovision surgery. Conclusion : The visual acuity, near stereoacuity and distance convergence fused amplitude were decreased after monovision surgery compared to progressive glasses multifocal contact lens wear, however, visual satisfaction in real life was improved.

The aim of this study was to optimize conditions for producing water-in-oil-in-water (W/O/W) nanoemulsion and spray-dried nanocapsule of red ginseng extract. Based on emulsion stability and average particle size analysis, optimum conditions to produce W/O/W nanoemulsion were: ratio of core to coating material, 3:7; primary emulsifier, 10% polyglycerol polyricinoleate; ratio of W/O phase to coating material, 1.5:8.5; secondary emulsifier, 10% polyoxyethylene sorbitan monolaurate; solvent, 20% ethyl acetate; secondary coating material, 10% maltodextrin (MD). Under these optimized conditions, particle size of spray-dried nanocapsules coated with MD of red ginseng ranged from 100 nm to 500 nm, based on response surface methodology with the highest yield (up to 99.7%). Results of the present study can be used to further optimize conditions to produce W/O/W nanoemulsion and spray-dried nanocapsule of red ginseng extract.

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic syndrome that occurs when susceptible individuals are exposed to triggering agents. Variability in the order and time of occurrence of symptoms often makes clinical diagnosis difficult. A late diagnosis or misdiagnosis of delayed-onset MH may lead to fatal complications. We herein report a case of delayed-onset MH in the postoperative recovery room. A 77-year-old man awoke from anesthesia and was transferred to the recovery room. Ten minutes after his arrival, his mental status became stuporous and he developed masseter muscle rigidity, hyperventilation, and a body temperature of 39.8°C. The patient was suspected to have MH, and 60 mg of dantrolene sodium (1 mg/kg) was administered via intravenous drip with symptomatic treatment. Within 10 minutes of dantrolene administration, the patient’s clinical signs subsided. This case report demonstrates that rapid diagnosis and treatment are crucial to ensure a good prognosis for patients with MH. A high level of suspicion based on clinical symptoms and early administration of therapeutic drugs such as dantrolene will also improve the clinical course. Therefore, suspicion and prompt diagnosis are absolutely essential. This case report emphasizes the importance of continuous education in the diagnosis and treatment of MH.

Background Patient safety in the intensive care unit (ICU) is one of the most critical issues, and unplanned extubation (UE) is considered the most adverse event for patient safety. Prevention and early detection of such an event is an essential but difficult component of quality care. Objective This study aimed to develop and validate prediction models for UE in ICU patients using machine learning. Methods This study was conducted in an academic tertiary hospital in Seoul, Republic of Korea. The hospital had approximately 2000 inpatient beds and 120 ICU beds. As of January 2019, the hospital had approximately 9000 outpatients on a daily basis. The number of annual ICU admissions was approximately 10,000. We conducted a retrospective study between January 1, 2010, and December 31, 2018. A total of 6914 extubation cases were included. We developed a UE prediction model using machine learning algorithms, which included random forest (RF), logistic regression (LR), artificial neural network (ANN), and support vector machine (SVM). For evaluating the model’s performance, we used the area under the receiver operating characteristic curve (AUROC). The sensitivity, specificity, positive predictive value, negative predictive value, and F1 score were also determined for each model. For performance evaluation, we also used a calibration curve, the Brier score, and the integrated calibration index (ICI) to compare different models. The potential clinical usefulness of the best model at the best threshold was assessed through a net benefit approach using a decision curve. Results Among the 6914 extubation cases, 248 underwent UE. In the UE group, there were more males than females, higher use of physical restraints, and fewer surgeries. The incidence of UE was higher during the night shift as compared to the planned extubation group. The rate of reintubation within 24 hours and hospital mortality were higher in the UE group. The UE prediction algorithm was developed, and the AUROC for RF was 0.787, for LR was 0.762, for ANN was 0.763, and for SVM was 0.740. Conclusions We successfully developed and validated machine learning–based prediction models to predict UE in ICU patients using electronic health record data. The best AUROC was 0.787 and the sensitivity was 0.949, which was obtained using the RF algorithm. The RF model was well-calibrated, and the Brier score and ICI were 0.129 and 0.048, respectively. The proposed prediction model uses widely available variables to limit the additional workload on the clinician. Further, this evaluation suggests that the model holds potential for clinical usefulness.

Pear scab caused by Venturia nashicola has been reported as an important disease of pear resulting in lowering the quality of pear fruits. In this study, it was conducted to investigate the relationship between resistance of V. nashicola and mutation of β-tubulin gene and the fungicide resistance in field isolate group in benzimidazole fungicides. Responce of V. nashicola to carbendazim could be classified into 3 groups as sensitive that does not grow at all on PDA amended with 0.16 μg/ml of carbendazim, low resistance that could not grow in 4.0 μg/ml medium, and high resistance that can grow even at 100 μg/ml. Thirty isolates of V. nashicola collected from 3 regions as Wonju, Naju, and Okcheon were highly resistant to carbendazim. Analysis of the nucleotide sequence of β-tubulin gene of V. nashicola showed that there was no difference in the nucleotide sequence between the sensitive and the low-resistant isolate, but GAG at codon 198 (glutamic acid) was replaced with GCG (alanine) in the high-resistant isolate. Among 10 isolates obtained from the Okcheon, 5 isolates showed the substitution of glycine for glutamic acid, which were resistant to carbendazim, but more sensitive to the mixture of carbendazim and diethofencarb than others. Through these results, all isolates of V. nashicola isolated in pear orchard were found to be resistant to benzimidazoles. Also, mutants E198A and E198G at β-tubulin were found to be important mechanisms of V. nashicola resistance against benzimidazole fungicides.

Rationale: Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. As most patients undergoing rigid bronchoscopy have moderate to severe respiratory disease or central airway obstruction, the operators often face the risk of hypoxemia when inserting the rigid bronchoscope into the patients’ airway. Applying high flow nasal cannula (HFNC) oxygen therapy before the insertion of the bronchoscope allows to maintain high fractional inspired oxygen (FiO2) and thus leading to maximizing apnea time before desaturation. Patient concerns and diagnosis: Case 1: A 70-year-old female patient was diagnosed with lung cancer in the left lower lobe and a tracheal mass of about 2.6 cm ∗ 0.8 cm in size. Case 2: A male patient, 77 years old, 55.7 kg and 157.3 cm in height, had been diagnosed with chronic obstructive pulmonary disease, and was scheduled for the bronchoscopic volume reduction surgery upon exacerbation of his symptoms of dyspnea and cough with sputum. Interventions: Preoxygenation was performed with HFNC (Fisher&Paykel Optiflow ThriveTM, New Zealand) for 3 minutes before the administration of anesthetic medications. The oxygen flow was set at 50 L/min and the FiO2 at 1.0. SpO2 increased to 100%. Outcomes: The HFNC oxygen has shown its effectiveness in safely maintaining the patients’ SpO2 during the prolonged apneic period of inserting bronchoscope. Lessons: HFNC oxygen is an effective tool in oxygenating the patients during the induction of rigid bronchoscopy, and that it may be a superior alternative to the conventional method of preoxygenation.

Objective The present study aimed to investigate patients’ characteristics that can affect the dose of propofol required to sedate children undergoing imaging. Methods In this retrospective, observational study, we reviewed medical records of children aged 0 to 18 years who were classified as having American Society of Anesthesiologists status 1 or 2 and they underwent imaging under propofol sedation between January 2011 and August 2016. Collected data included patients’ demographics, propofol doses, duration of sedation, and complications. Regression analysis was performed to determine patients’ characteristics that may affect the dose of propofol required to induce sedation. Results A total of 925 patients were included. Simple linear regression showed that the dose of propofol was correlated with age, height, weight, and body surface area. Using the results of multiple linear regression, the following formula was used to estimate the dose of propofol (mg) for sedation: 0.75 + 0.14 × age (months) + 45.82 × body surface area (m2). Conclusion A child’s age, height, and body surface area should be considered when deciding the induction dose of propofol. Additionally, the formula that we have proposed can be used to estimate the dose of propofol required to induce sedation in children undergoing imaging.

Middle East respiratory syndrome (MERS) coronavirus was found by reverse-transcription polymerase-chain-reaction from viral cultures of 4 of 7 air samples and 15 of 68 surface swabs from 3 MERS patients' rooms, calling for epidemiologic investigation for contact and airborne transmission., Background. The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. Methods. We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). Results. The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. Conclusions. These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.

Introduction Venous air embolism (VAE) from vascular injuries, is of rare occurrence but can result in catastrophic complications during total hip arthroplasty (THA). Early recognition and prompt management of vascular injury are required to avoid severe complications. Especially, bleeding is generally associated with profound hypotension in venous injury. We report an unusual complication of venous air embolism induced by femoral vein rupture during THA. Patient concerns A 54-year-old male patient with a history of old left acetabular fracture was scheduled for THA. We experienced massive bleeding and VAE induced by femoral vein rupture during total hip arthroplasty. The BP suddenly dropped from 100/70 mm Hg to 80/50 mm Hg with massive bleeding. ETCO2 and SaO2 decreased profoundly. Diagnosis The VAE was diagnosed by the change in end- tidal CO2 (ETCO2) and change of vital signs, so we performed ABGA and inserted TEE for confirmination. Interventions For treatment, patient was managed by oxygen therapy, inotropics, vasopressor, transfusion and surgical repair. Outcomes Upon consulting with a cardiologist, the patient was extubated the next day and was transferred to the general ward and recovered without serious complications. He stayed for 17 days until finally discharged without complications. Conclusion Preoperative vascular imaging may be recommended in the revisional case of THA or in patients with the history of hip trauma. The monitoring of ETCO2 and TEE might be helpful to recognize VAE earlier and therefore to avoid catastrophic complications through adequate treatment.

Background: Previous studies on of the dissociative subtype of posttraumatic stress disorder (d-PTSD) have relied on specialized statistical methods (i.e. profile or class analyses) for diagnosis than clinical rating available to clinicians. Objective: This study investigated the prevalence and covariates of d-PTSD diagnosed by a semi-structured interview in a cohort of outpatients with DSM-IV PTSD in a specialized trauma clinic in South Korea. Method: Data from 249 patients with civilian PTSD were examined, including demographics, clinical variables, Clinical Global Impression (CGI) Scale, and Clinician-Administered PTSD Scale (CAPS-IV). We defined d-PTSD as the presence of either depersonalization or derealization according to additional dissociative items of the CAPS. About one third (n = 82, 32.9%) of patients were designated as having d-PTSD. Results: Compared to the other patients with PTSD, those with d-PTSD were younger, had more severe PTSD symptoms, frequent interpersonal trauma, and a higher number of comorbid disorders. When these variables and their interactions were entered into a logistic regression model, younger age, severe PTSD symptoms and two or more comorbid conditions remained for the final model. We did not find a significant difference in improvement over the course of treatment between two groups. Conclusions: This study highlights the high prevalence of d-PTSD in a clinical population. Associated features of d-PTSD were similar to those reported in the Euro-American literature. Further studies are needed to better understand mechanisms and treatment options for d-PTSD. • About one-third of PTSD patients in a clinical cohort were diagnosed as d-PTSD. • d-PTSD group was younger and had severe PTSD symptoms and more psychiatric comorbidities. • Rates of d-PTSD may be higher when the diagnoses were made with clinical interviews.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea. The tick-borne virus that causes SFTS has infected more than 5,000 humans, with a 6.4% to 20.9% fatality rate. Currently, there are no prophylactic or therapeutic measures against this virus. Historically, antibodies from patients who recovered from viral infection have been used to treat new patients, and commercially available antiviral monoclonal antibodies have been developed. Palivizumab was approved for the prophylaxis of respiratory syncytial virus (RSV) infection, and ibalizumab-uiyk was recently approved for the treatment of human immunodeficiency virus (HIV)-infected patients. To develop an antiviral monoclonal antibody for SFTS patients, we selected 10 antibodies from a patient who recovered from SFTS and found that one antibody potently inhibited SFTS viral infection both in vitro and in animal studies. We mapped the binding site of this antibody on the SFTS virus, which allowed us to predict that this antibody could bind 247 out of the 272 SFTS virus isolates reported to date. We anticipate that this antibody could be developed into a therapeutic treatment against SFTS.

Background: There is a risk of drug sorption into an intravenous administration set composed of polyvinyl chloride (PVC), polyurethane (PU), or polyolefin (PO). This has implications on the dose of the active ingredient the patient receives, and thus therapeutic success. This study aimed to determine the plasma concentration of nitroglycerin and the effect of nitroglycerin on patients based on the composition of the administration set. Methods: Using a randomized, open-labeled, 3 × 3 crossover method, 9 volunteers were assigned to 3 groups. In period I, nitroglycerin (100 μg/mL) was infused via a PVC- (group A), PU- (group B), or PO-based (group C) administration set. In period II, PU- (group A), PO- (group B), and PVC-based (group C) administration sets were used, and in period III, PO- (group A), PVC- (group B), and PU-based (group C) administration sets were used. The rate of drug administration in all periods was 12 mL/hour for 30 minutes using an infusion pump. Blood samples were collected, and the plasma concentrations of nitroglycerin were analyzed using validated high-performance liquid chromatography coupled with tandem mass spectrometry. Blood pressure was determined using a sphygmomanometer applied to the other upper arm at an interval of 5 minutes. Results: We observed that the mean plasma concentration of nitroglycerin over time when administered using a PO-based tube was higher than that when using a PU- or PVC-based tube. When the percent change of the mean arterial pressure from baseline at each time point was compared among groups, there were statistically significant differences between PU and PO or PVC at most points during nitroglycerin infusion. Conclusion: Our results showed higher nitroglycerin plasma concentration and lower arterial pressure when a PO-based administration set was used than when a PVC- or PU-based administration set was used. PO-based administration sets may be more appropriate for nitroglycerin administration compared to those composed of PVC or PU.

An importance of infrastructures’ protection against crash or blast loading has been an emerging issue as structures are becomi ng much bigger and population densities in downtown are growing up. However, there exists no such a standard to evaluate the protection perfor mance of construction material itself. Prior to building standards for protection assessment techniques, this study performed gas-gun propelled proje ctile impact tests with series of contact-type monitoring systems to investigate the applicability of each sensing type. Through the impact tests, failure mod es and protection performances of both normal concrete and UHPC (Ultra High Performance Concrete) reinforced by steel fibers were also evaluated. The results showed that LVDT could be applicable for the impact test among contact-type sensors and UHPC with fibers had a remarkable potential to improve protect ion against impact loading.Keywords: Crash, Impact, Protection, Gas-gun, Ultra High Performance Concrete, Monitoring