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Abstract Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining “cold” and “hot” human triple negative breast cancers (TDLNCold and TDLNHot). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLNCold. Two gene pairs (TBX21/GATA3-CXCR1) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLNCold. This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLNCold versus TDLNHot. Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLNCold. Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4+ MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors.

Abstract Background The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML. Methods Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing. Individual mouse monoclonal antibodies (mAbs) were produced and characterized, from which we generated BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. Mutations in human IgG1 Fc were introduced to reduce FcγR binding. The antileukemic activity of BIF002 was characterized in vitro and in vivo using multiple cell lines and patient derived AML samples. Results IL1RAP was found to be highly expressed on most human AML cell lines and primary blasts, including CD34+ LSC-enriched subpopulation from patients with both de novo and relapsed/refractory (R/R) leukemia, but not on normal HSCs. In co-culture of T cells from healthy donors and IL1RAPhigh AML cell lines and primary blasts, BIF002 induced dose- and effector-to-target (E:T) ratio-dependent T cell activation and leukemic cell lysis at subnanomolar concentrations. BIF002 administered intravenously along with human T cells led to depletion of leukemic cells, and significantly prolonged survival of IL1RAPhigh MOLM13 or AML patient-derived xenografts with no off-target side effects, compared to controls. Of note, BiF002 effectively redirects T cells to eliminate LSCs, as evidenced by the absence of disease initiation in secondary recipients of bone marrow (BM) from BIF002+T cells-treated donors (median survival not reached; all survived > 200 days) compared with recipients of BM from vehicle- (median survival: 26 days; p = 0.0004) or isotype control antibody+T cells-treated donors (26 days; p = 0.0002). Conclusions The novel anti-IL1RAP/CD3 TCE, BIF002, eradicates LSCs and significantly prolongs survival of AML xenografts, representing a promising, novel treatment for AML.

Abstract Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

A solar-driven photoelectrochemical (PEC) cell is emerging as one of the promising clean hydrogen generation systems. Engineering of semiconductor heterojunctions and surface morphologies of photoelectrodes in a PEC cell has been a primitive approach to boost its performance. This study presents that a molybdenum disulfide (MoS2) nanoflakes photoanode on 3-dimensional (3D) porous carbon spun fabric (CSF) as a substrate effectively enhances hydrogen generations due to sufficiently enlarged surface area. MoS2 is grown on CSFs utilizing a hydrothermal method. Among three different MoS2 coating morphologies depending on the amount of MoS2 precursor and hydrothermal growth time, film shape MoS2 on CSFs had the largest surface area, exhibiting the highest photocurrent density of 26.48 mA/cm2 and the highest applied bias photon-to-current efficiency (ABPE) efficiency of 5.32% at 0.43 VRHE. Furthermore, with a two-step growth method of sputtering and a subsequent hydrothermal coating, continuous TiO2/MoS2 heterojunctions on a porous CSF further promoted the photoelectrochemical performances due to their optimized bandgap alignments. Enlarged surface area, enhanced charge transfer, and utilization of visible light enable a highly efficient MoS2/TiO2/CSF photoanode with a photocurrent density of 33.81 mA/cm2 and an ABPE of 6.97 % at 0.87 VRHE. The hydrogen generation amount of the PEC cell with MoS2/TiO2/CSF photoanode is 225.4 μmol/L after light irradiation of 60 s.

Abstract We report on the synthesis of large-area molybdenum disulfide (MoS2) film on an insulating substrate by means of chemical vapor deposition. A single mixture of molybdenum hexacarbonyl (Mo(CO)6) and dimethyl disulfide (C2H6S2) was utilized as an organic liquid precursor for the synthesis of MoS2 film. Carbon impurities stemming from the dissociation of the organic precursor are effectively removed by water oxidation, and hydrogen gas, which is a by-product of the oxidation of carbon impurities, inhibits the formation of molybdenum oxides. The use of a liquid precursor assisted with water oxidation ensures high reproducibility and full-coverage of MoS2 film for large area, which is not typically achieved with solid precursors such as molybdenum oxide and sulfur powder. We believe that our approach will advance the synthesis of transition metal dichalcogenides.

Although young children demonstrate knowledge of fairness norms, their actual sharing is often inconsistent with their understanding. A possible explanation for this discrepancy is the failure of behavioral control in young children. Thus, the present research manipulated behavioral control experimentally and examined its effect on the sharing behavior in 3- to 4-year-olds (N = 64). Children were randomly assigned to either the behavioral control or the neutral prime conditions. In the behavioral control prime condition, the children listened to a story in which a protagonist exerted behavioral control actively, refraining from eating candies. In the neutral prime condition, the children listened to a story in which a protagonist did not explicitly engage in behavioral control. The children then participated in the dictator game. The experimenter asked the children to share as many stickers as they wanted or should with an anonymous child. Children in the behavioral control prime condition shared more stickers than those in the neutral prime condition. However, the two groups did not differ in their judgments of fairness and emotional experiences. The current research provides evidence that preschoolers’ sharing behaviors can be facilitated by behavioral control.

Introduction: The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions. Methods: The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/ electromyographic) recording and cognitive behavior measures were collected. Results: The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount. Discussion: Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males. [ABSTRACT FROM AUTHOR]

Background/Aims In serological tests for Helicobacter pylori (H. pylori), an enzyme-linked immunosorbent assay (GENEDIA®) and a solid-phase, two-step chemiluminescent enzyme immunoassay (IMMULITE®), which are easy to perform, inexpensive, and widely available, are commonly used. However, local validation of the test performance of IMMULITE® is required. This study aimed to examine the performance of IMMULITE® in comparison with that of GENEDIA® in a Korean health checkup population. Materials and Methods The sera of 300 subjects among those who underwent health checkup were analyzed using IMMULITE®, and results were compared with those of GENEDIA®. The two serological tests were compared for their ability to predict atrophic gastritis (AG) or intestinal metaplasia (IM) on endoscopy. Results We found significant correlation (Pearson correlation coefficient=0.903, P

For improved examination of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE), bowel preparation is an essential issue. Multiple factors like air bubbles, food material in the small bowel, and gastric and small bowel transit time affect the small bowel visualization quality (SBVQ), diagnostic yield (DY) and cecal completion rate (CR). Bowel preparation with polyethylene glycol (PEG) solution enhances SBVQ and DY, but it has no effect on CR. Bowel preparation with PEG solution 2 L is similar to PEG 4 L in SBVQ, DY, and CR. Bowel preparation with fasting or PEG solution combined with anti-foaming agents like simethicone enhance SBVQ, but it has no effect on CR. Bowel preparation with prokinetics is not commonly recommended. Optimal timing for purgative bowel preparation has yet to be established. However, the studies regarding bowel preparation for DAE are not sufficient. European Society of Gastrointestinal Endoscopy (ESGE) recommends 8-12 hours fasting from solid food and 4-6 hours fasting from liquids prior to the antegrade DAE. For retrograde DAE, colonoscopy preparation regimen is recommended. This article reviews the literature and ESGE, 2013 Korean published guidelines regarding bowel preparation for VCE and DAE, following suggestion for optimal bowel preparation for VCE and balloon enteroscopy.

Children autonomously make sound moral judgments based on internal criteria, but they tend to make erroneous judgments in the presence of social influences, and the reasons for these errors are not well understood. Thus, the current research investigated how the presence of observers who can see and listen to 3-year-old children's judgments but who do not present their opinions influences children's conformity in moral judgment behavior. In Experiment 1, the children (N = 30) were presented with pictures depicting prosocial behaviors and asked whether the behaviors were acceptable. The children's tendency to change their answers after hearing the counterintuitive opinions of informants was then measured. The results showed that the children's moral judgments were more likely to conform to that of the group in the presence of observers. Experiment 2 aimed to determine the reason children were more likely to conform to a group when being watched by observers in Experiment 1. Children (N = 30) were randomly assigned to two conditions with different observer conditions as follows. Observers were either wearing headsets, indicating that they could not hear the children's responses, or had them hanging around their necks, indicating that they could. The results showed that children's conformity behavior depended on whether observers could hear what they were saying. The current findings are expected to help elucidate not only social factors that affect children's moral judgments but also the developmental mechanism of an observer effect. [ABSTRACT FROM AUTHOR]

SMURF2 is a member of the HECT family of E3 ubiquitin ligases that have important roles as a negative regulator of transforming growth factor‐β (TGF‐β) signaling through ubiquitin‐mediated degradation of TGF‐β receptor I. However, the regulatory mechanism of SMURF2 is largely unknown. In this study, we identified that micro(mi)R‐195 and miR‐497 putatively target SMURF2 using several target prediction databases. Both miR‐195 and miR‐497 bind to the 3′‐UTR of the SMURF2 mRNA and inhibit SMURF2 expression. Furthermore, miR‐195 and miR‐497 regulate SMURF2‐dependent TβRI ubiquitination and cause the activation of the TGF‐β signaling pathway in lung cancer cells. Upregulation of miR‐195 and miR‐497 significantly reduced cell viability and colony formation through the activation of TGF‐β signaling. Interestingly, miR‐195 and miR‐497 also reduced the invasion ability of lung cancer cells when cells were treated with TGF‐β1. Subsequent in vivo studies in xenograft nude mice model revealed that miR‐195 and miR‐497 repress tumor growth. These findings demonstrate that miR‐195 and miR‐497 act as a tumor suppressor by suppressing ubiquitination‐mediated degradation of TGF‐β receptors through SMURF2, and suggest that miR‐195 and miR‐497 are potential therapeutic targets for lung cancer.

This paper analyzes delta-Vs to maintain an extremely low altitude on the Moon and investigates the possibilities of performing a CubeSat mission. To formulate the station-keeping (SK) problem at an extremely low altitude, current work has utilized real-flight performance proven software, the Systems Tool Kit Astrogator by Analytical Graphics Inc. With a high-fidelity force model, properties of SK maneuver delta-Vs to maintain an extremely low altitude are successfully derived with respect to different sets of reference orbits; of different altitudes as well as deadband limits. The effect of the degree and order selection of lunar gravitational harmonics on the overall SK maneuver strategy is also analyzed. Based on the derived SK maneuver delta-V costs, the possibilities of performing a CubeSat mission are analyzed with the expected mission lifetime by applying the current flight-proven miniaturized propulsion system performances. Moreover, the lunar surface coverage as well as the orbital characteristics of a candidate reference orbit are discussed. As a result, it is concluded that an approximately 15-kg class CubeSat could maintain an orbit (30–50 km reference altitude having ±10 km deadband limits) around the Moon for 1–6 months and provide almost full coverage of the lunar surface.

In this study, orbit determination (OD) simulation for the Korea Pathfinder Lunar Orbiter (KPLO) was accomplished for investigation of the observational arc-length effect using a sequential estimation algorithm. A lunar polar orbit located at 100 km altitude and 90° inclination was mainly considered for the KPLO mission operation phase. For measurement simulation and OD for KPLO, the Analytical Graphics Inc. Systems Tool Kit 11 and Orbit Determination Tool Kit 6 software were utilized. Three deep-space ground stations, including two deep space network (DSN) antennas and the Korea Deep Space Antenna, were configured for the OD simulation. To investigate the arc-length effect on OD, 60-hr, 48-hr, 24-hr, and 12-hr tracking data were prepared. Position uncertainty by error covariance and orbit overlap precision were used for OD performance evaluation. Additionally, orbit prediction (OP) accuracy was also assessed by the position difference between the estimated and true orbits. Finally, we concluded that the 48-hr-based OD strategy is suitable for effective flight dynamics operation of KPLO. This work suggests a useful guideline for the OD strategy of KPLO mission planning and operation during the nominal lunar orbits phase.

Background The role of clinical pharmacists in medication therapy to improve clinical and economic outcomes has been reported in the literature. This study was conducted to analyze the changes in details of medication interventions before and after the introduction of clinical pharmacists into the care of neurocritical care unit (NCU) patients, and to evaluate the economic effects of clinical pharmacists by calculating the avoidance cost. Methods A retrospective study was conducted reviewing the electronic medical records from June 2013 to May 2014 (before), and from June 2016 to May 2017 (after). We calculated the number and rates of intervention, the acceptance rates of it, and also reviewed the list of interventions. We calculated avoidance cost if there was no intervention. Results The monthly mean number of interventions increased from 8.0 (±5.7) to 31.7 (±12.8) (P

Background/Aims: The aim of this study was to analyze the trend of the prevalences of atrophic gastritis (AG) and intestinal metaplasia (IM) from 2011 to 2016∼2017 in Korea. And, the risk factors of AG and IM were compared between 2011 and 2016∼2017. Materials and Methods: A total of 4,023 subjects in 2011 and 2,506 subjects in 2016∼2017 were enrolled. AG and IM were diagnosed on the basis of endoscopic findings. Multivariate analysis was performed for risk factors of AG and IM. Seventeen factors were analyzed. Results: The seroprevalence of Helicobacter pylori decreased from 2011 (59.8%; 2,407/4,023) to 2016∼2017 (51.6%; 1,293/2,506; P＜ 0.001). The prevalence of AG decreased from 2011 to 2016∼2017 (P=0.018), but that of IM increased (P＜ 0.001). The risk factors of AG in 2011 were male sex, old age, H. pylori immuoglobulin G (IgG) positivity, family history of gastric cancer (GC), and high-salt diet. For IM in 2011, the risk factors were male sex, old age, H. pylori IgG positivity, and family history of GC. Risk factors of AG in 2016∼2017 were old age, H. pylori IgG positivity, and country of residence. For IM in 2016∼2017, the risk factors were male sex, old age, family history of GC, high fasting glucose level (≥126 mg/dL), H. pylori IgG positivity, and low income level. Conclusions: The difference in prevalence trends of AG and IM between 2016∼2017 and 2011 could be the result of the different risk factors of AG and IM, such as decreased prevalence of H. pylori infection.

Background: Phospholipase A2 receptor (PLA2R) has been identified as a major autoantigen in primary membranous nephropathy (MN). We evaluated the association between anti-PLA2R antibodies and clinical outcome in Korean patients with primary MN. Methods: A total of 66 patients with biopsy-proven MN were included. Serum level of anti-PLA2R antibodies was measured by enzyme-linked immunosorbent assay. Biochemical parameters were estimated initially and at follow-up. Results: Anti-PLA2R antibodies were detected in 52.1% and 27.8% of patients with primary and secondary MN, respectively. Forty-eight patients with primary MN were grouped based on presence or absence of anti-PLA2R antibodies. Proteinuria was more severe in anti-PLA2R-positive patients than in anti-PLA2R-negative patients (urine rotein/creatinine ratio 7.922 ± 3.985 g/g vs. 4.318 ± 3.304 g/g, P = 0.001), and anti-PLA2R antibody level was positively correlated with proteinuria. The incidence of chronic kidney disease stage ≥ 3 was higher in anti-PLA2R-positive patients compared with anti-PLA2R-negative patients (P = 0.004). The probabilities of spontaneous remission were higher in anti-PLA2R-negative patients compared with anti-PLA2R-positive patients (P⟨ 0.001). Multivariate analysis demonstrated that anti-PLA2R antibodies are an independent risk factor for developing chronic kidney disease stage ≥ 3 and for not reaching spontaneous remission. Conclusion: Detection of anti-PLA2R antibodies at diagnosis in patients with primary MN can predict prognosis and guide treatment decisions.

A 20-year-old Cambodian male living in Korea for 2 years as a foreign worker visited our gastroenterology outpatient clinic. He had a small farm in Cambodia. He complained of postprandial upper abdominal pain with nausea and vomiting for 2 years. Gastroduodenoscopy showed hyperemic mucosa near the major papilla in the duodenum and two small and slender reddish worms. These were removed with endoscopic biopsy forceps. Under microscopy, these were identified as Ancylostoma duodenale by the characteristic morphology of 2 pairs of cutting teeth in the buccal cavity and 3 lobes in the copulatory bursa. After removal of two worms, his symptom improved. Soil-transmitted helminths (STH) present a global health problem. In the Republic of Korea, STH, including hookworms, were highly prevalent until the 1970s. With mass fecal examination followed by selective mass chemotherapy with anthelmintics from 1969 to 1995, the prevalence of STH has rapidly decreased since the 1980s. Since 2004, no hookworms have been found in nationwide surveys on the prevalence of intestinal parasitic infection. Therefore, we report a case of in vivo endoscopic removal of A. duodenale in a patient with abdominal pain.

The first Korea lunar orbiter, Korea Pathfinder Lunar Orbiter (KPLO), has been in development since 2016. After launch, the KPLO will execute several maneuvers to enter into the lunar mission orbit, and will then perform lunar science missions for one year. Among these maneuvers, the lunar orbit insertion (LOI) is the most critical maneuver because the KPLO will experience an extreme velocity change in the presence of the Moon`s gravitational pull. However, the lunar orbiter may have a delayed LOI burn during operation due to hardware limitations and telemetry delays. This delayed burn could occur in different captured lunar orbits; in the worst case, the KPLO could fly away from the Moon. Therefore, in this study, the burn delay for the first LOI maneuver is analyzed to successfully enter the desired lunar orbit. Numerical simulations are performed to evaluate the difference between the desired and delayed lunar orbits due to a burn delay in the LOI maneuver. Based on this analysis, critical factors in the LOI maneuver, the periselene altitude and orbit period, are significantly changed and an additional delta-V in the second LOI maneuver is required as the delay burn interval increases to 10 min from the planned maneuver epoch.

Abstract Background Despite many high-quality programs in basic surgical-skill education, the surgical skill of junior doctors varies widely. This, together with the waning interest in surgery as a career among medical students, is a serious issue confronted by hospitals and healthcare systems worldwide. We, therefore, developed and implemented an intensive one-day surgical-skill training course for two purposes; it would improve surgical skills and increase interest in surgery among medical students. Methods The surgical-skill training program is named Surgical Skill Weekend (SSW) and it includes hands-on training sessions for surgical-suturing techniques and advanced surgical procedures (i.e. laparoscopic and robot-assisted surgery), hybrid simulation sessions, and an operating-room session where aforementioned sessions are all put together. By the end of the program, students’ improvements in surgical-suturing skills were assessed by experts in a form of checklist, and changes in the interest in a surgical career, if there were any, were answered by the students who participated in the program. Results A total of ninety-one (91) medical students participated in the 2015 and 2016 SSW courses. Their overall satisfaction level with the course was very high (Very satisfied: 78%, Quite satisfied: 22%). All of the participant’s surgical-suturing skills significantly improved (median score range: 14–20, P

To ensure the successful launch of the Korea pathfinder lunar orbiter (KPLO) mission, the Korea Aerospace Research Institute (KARI) is now performing extensive trajectory design and analysis studies. From the trajectory design perspective, it is crucial to prepare contingency trajectory options for the failure of the first lunar brake or the failure of the first lunar orbit insertion (LOI) maneuver. As part of the early phase trajectory design and analysis activities, the required time of flight (TOF) and associated delta-V magnitudes for each recovery maneuver (RM) to recover the KPLO mission trajectory are analyzed. There are two typical trajectory recovery options, direct recovery and low energy recovery. The current work is focused on the direct recovery option. Results indicate that a quicker execution of the first RM after the failure of the first LOI plays a significant role in saving the magnitudes of the RMs. Under the conditions of the extremely tight delta-V budget that is currently allocated for the KPLO mission, it is found that the recovery of the KPLO without altering the originally planned mission orbit (a 100 km circular orbit) cannot be achieved via direct recovery options. However, feasible recovery options are suggested within the boundaries of the currently planned delta-V budget. By changing the shape and orientation of the recovered final mission orbit, it is expected that the KPLO mission may partially pursue its scientific mission after successful recovery, though it will be limited.

Chromosomal microarray (CMA) is a high-resolution, high-throughput method of identifying submicroscopic genomic copy number variations (CNVs). CMA has been established as the first-line diagnostic test for individuals with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCAs). CMA analysis was performed in 42 Korean patients who had been diagnosed with unexplained DD, ID, ASDs, and MCAs. Clinically relevant CNVs were discovered in 28 patients. Variants of unknown significance were detected in 13 patients. The diagnostic yield was high (66.7%). CMA is a superior diagnostic tool compared with conventional karyotyping and fluorescent in situ hybridization.

Background/Aims: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), has been reported to have various ophthalmologic manifestations. The aim of this study was to evaluate the prevalence of ophthalmologic manifestations associated with IBD in Korea.Methods: Sixty-one patients were examined between May 2013 and October 2014. We performed complete ophthalmologic examinations.Results: Findings included 36 patients with CD and 25 with UC. The mean age of the patients was 34±16 years and disease duration was 45.3±23.9 months. Ophthalmologic manifestations were positive in 44 cases. Primary complication was diagnosed in 5 cases, as follows; iritis in 2 cases, episcleritis in one case, iritis with optic neuritis in 1 case, and serous retinal detachment in 1 case, without secondary complications. The most common coincidental complication was dry eye syndrome (DES), in 35 patients (57.4%). The prevalence of DES in the control group was 21.3%. The proportion of DES in patients with IBD was significantly higher than in the control group (P=0.002).Conclusions: Ophthalmologic manifestations were high (72.1%) in IBD patients. Clinically significant primary ocular inflammation occurred in 8.2% of patients. The most common complication was DES. There was a higher rate of DES in patients with IBD compared to the control group. Evaluation of the eye should be a routine component in patients with IBD.

Abstract Background The aims of this study were to identify the clinical significances of the size of metastatic lymph node (mLN) and LN ratio (LNR) and to attempt to create a risk stratification for papillary thyroid carcinoma (PTC) patients. Methods We investigated the 435 PTC patients who underwent radioactive iodine (RAI) ablation treatment following thyroid surgery. The patients were classified into two groups (micrometastasis (pN1mic) ≤ 0.2 cm and macrometastasis (pN1mac) > 0.2 cm) and were stratified into the following three risk groups: group I (pN1mic, LNR ≤ 0.5); group II (pN1mic, LNR > 0.5 or pN1mac, LNR ≤ 0.5); and group III (pN1mac with LNR > 0.5). And then we investigated the association of the classified groups and variable clinicopathologic factors. Results The clinical characteristics such as large tumor size, extrathyroidal extension, higher T stage, and greater number of mLN or LNR were significantly associated with pN1mac. The mean stimulated thyroglobulin levels were increased with the patient risk groups (p = 0.02). The recurrence-free survivals were significantly different between the stratified groups (p = 0.001). Conclusions The patient groups I, II, and III may be referred to as low-, intermediate-, and high-risk groups. Clinicians should consider the possibility of recurrence, and the decisions about the application of RAI ablation based on the size of mLN and the patient’s risk groups.

The current research examined how infants exploit linguistic information to update an agent’s false belief about an object’s location. Fourteen- to eighteen-month-old infants first watched a series of events involving two agents, a ball, and two containers (a box and a cup). Agent1 repeatedly acted on the ball and then put it in the box in the presence of agent2. Then agent1 disappeared from the scene and agent2 switched the ball’s location from the box to the cup. Upon agent1’s return, agent2 told her, “The ball is in the cup!” Agent1 then reached for either the cup (cup event) or the box (box event). The infants looked reliably longer if shown the box event as opposed to the cup event. However, when agent2 simply said, “The ball and the cup!” – which does not explicitly mention the ball’s new location – infants looked significantly longer if shown the cup event as opposed the box event. These findings thus provide new evidence for false-belief understanding in infancy and suggest that infants expect an agent’s false belief to be updated only by explicit verbal information.

Capsule endoscopy (CE) quality control requires an objective scoring system to evaluate the preparation of the small bowel (SB). We propose a deep learning algorithm to calculate SB cleansing scores and verify the algorithm’s performance. A 5-point scoring system based on clarity of mucosal visualization was used to develop the deep learning algorithm (400,000 frames; 280,000 for training and 120,000 for testing). External validation was performed using additional CE cases (n = 50), and average cleansing scores (1.0 to 5.0) calculated using the algorithm were compared to clinical grades (A to C) assigned by clinicians. Test results obtained using 120,000 frames exhibited 93% accuracy. The separate CE case exhibited substantial agreement between the deep learning algorithm scores and clinicians’ assessments (Cohen’s kappa: 0.672). In the external validation, the cleansing score decreased with worsening clinical grade (scores of 3.9, 3.2, and 2.5 for grades A, B, and C, respectively, p < 0.001). Receiver operating characteristic curve analysis revealed that a cleansing score cut-off of 2.95 indicated clinically adequate preparation. This algorithm provides an objective and automated cleansing score for evaluating SB preparation for CE. The results of this study will serve as clinical evidence supporting the practical use of deep learning algorithms for evaluating SB preparation quality.

In this study, the uncertainty requirements for orbit, attitude, and burn performance were estimated and analyzed for the execution of the 1st lunar orbit insertion (LOI) maneuver of the Korea Pathfinder Lunar Orbiter (KPLO) mission. During the early design phase of the system, associate analysis is an essential design factor as the 1st LOI maneuver is the largest burn that utilizes the onboard propulsion system; the success of the lunar capture is directly affected by the performance achieved. For the analysis, the spacecraft is assumed to have already approached the periselene with a hyperbolic arrival trajectory around the moon. In addition, diverse arrival conditions and mission constraints were considered, such as varying periselene approach velocity, altitude, and orbital period of the capture orbit after execution of the 1st LOI maneuver. The current analysis assumed an impulsive LOI maneuver, and two-body equations of motion were adapted to simplify the problem for a preliminary analysis. Monte Carlo simulations were performed for the statistical analysis to analyze diverse uncertainties that might arise at the moment when the maneuver is executed. As a result, three major requirements were analyzed and estimated for the early design phase. First, the minimum requirements were estimated for the burn performance to be captured around the moon. Second, the requirements for orbit, attitude, and maneuver burn performances were simultaneously estimated and analyzed to maintain the 1st elliptical orbit achieved around the moon within the specified orbital period. Finally, the dispersion requirements on the B-plane aiming at target points to meet the target insertion goal were analyzed and can be utilized as reference target guidelines for a mid-course correction (MCC) maneuver during the transfer. More detailed system requirements for the KPLO mission, particularly for the spacecraft bus itself and for the flight dynamics subsystem at the ground control center, are expected to be prepared and established based on the current results, including a contingency trajectory design plan.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

DYRK1A is important in neuronal development and function, and its excessive activity is considered a significant pathogenic factor in Down syndrome and Alzheimer's disease. Thus, inhibition of DYRK1A has been suggested to be a new strategy to modify the disease. Very few compounds, however, have been reported to act as inhibitors, and their potential clinical uses require further evaluation. Here, we newly identify CX-4945, the safety of which has been already proven in the clinical setting, as a potent inhibitor of DYRK1A that acts in an ATP-competitive manner. The inhibitory potency of CX-4945 on DYRK1A (IC50=6.8 nM) in vitro was higher than that of harmine, INDY or proINDY, which are well-known potent inhibitors of DYRK1A. CX-4945 effectively reverses the aberrant phosphorylation of Tau, amyloid precursor protein (APP) and presenilin 1 (PS1) in mammalian cells. To our surprise, feeding with CX-4945 significantly restored the neurological and phenotypic defects induced by the overexpression of minibrain, an ortholog of human DYRK1A, in the Drosophila model. Moreover, oral administration of CX-4945 acutely suppressed Tau hyperphosphorylation in the hippocampus of DYRK1A-overexpressing mice. Our research results demonstrate that CX-4945 is a potent DYRK1A inhibitor and also suggest that it has therapeutic potential for DYRK1A-associated diseases.

Background : /Aims: Obscure gastrointestinal bleeding (OGIB) accounts for 5% of all gastrointestinal (GI) bleeding cases. Dynamic contrast-enhanced multidetector-row CT (DCE-MDCT) is not generally recommended in OGIB patients due to its low sensitivity. However, it can be used to quickly and simply diagnose OGIB according to some guidelines. The aim of this study was to evaluate the clinical efficacy of DCE-MDCT in OGIB patients. Methods : : We retrospectively analyzed the medical records of 362 patients who underwent DCE-MDCT between March 2009 and January 2014. A total of 45 patients diagnosed with OGIB were included in this study. Their baseline characteristics and treatment procedure were analyzed retrospectively. The positive rates of DCE-MDCT for the detection of bleeding and associated factors were assessed. Results : : The mean age of the patients was 59 years, and males represented 51.1%. Melena was the most common symptom (44.4%). Positive rate of DCE-MDCT findings was 20.0% (9/45). Among these patients, intraluminal contrast extravasation was found in 5 patients (55.6%) and intraluminal hematoma or mass lesions were found in 2 patients each (22.2%). Thirty nine patients (86.7%) underwent conservative management, and 6 patients (13.3%) underwent specific treatment, such as endoscopic treatment, embolization, or surgery. Patients who showed positivity in DCE-MDCT more frequently received specific treatment compared with those who were negative (44.4% vs. 5.6%, p=0.010). Conclusion : s: Although DCE-MDCT showed a low positive rate (20.0%), positive findings of DCE-MDCT could lead to specific treatment. Positive DCE-MDCT findings play a useful role in the management of patients with OGIB. (Korean J Gastroenterol 2016;67:198-206)

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.

Small bowel capsule endoscopy (CE) was first introduced 15 years ago, and a large amount of literature has since been produced, focused on its indication, diagnostic yields, and safety. Guidelines that have made CE the primary diagnostic tool for small bowel disease have been created. Since its initial use in the small bowel, CE has been used for the esophagus, stomach, and colon. The primary indications for small bowel CE are obscure gastrointestinal bleeding, unexplained iron deficiency anemia, suspected Crohn's disease, small bowel tumors, nonsteroidal anti-inflammatory drug enteropathy, portal hypertensive enteropathy, celiac disease, etc. Colon CE provides an alternative to conventional colonoscopy, with possible use in colorectal cancer screening. Guidelines for optimal bowel preparation of CE have been suggested. The main challenges in CE are the development of new devices with the ability to provide therapy, air inflation for better visualization of the small bowel, biopsy sampling systems attached to the capsule, and the possibility of guiding and moving the capsule by an external motion controller. We review the current status and future directions of CE, and address all aspects of clinical practice, including the role of CE and long-term clinical outcomes.