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Introduction: Prostate cancer most commonly metastasizes to the bone and lymph nodes. Gastrointestinal metastasis has been noted in the literature but appears to be an exceedingly uncommon phenomenon. Large intestinal involvement in particular has been reported on only a few occasions, and never concomitantly with small intestinal metastatic involvement. Case Report: We report the case of a 69-year-old gentleman with metastatic castrate-resistant prostate cancer with development of gastrointestinal symptomatology with extensive investigation eventually revealing small and large intestinal polyps subsequently confirmed to be representative of metastatic prostate cancer. Conclusion: This case demonstrates the importance of maintaining a wide differential diagnosis in the context of gastrointestinal symptomatology in malignancy. Thorough endoscopic evaluation may be necessary in such cases in order to identify potential metastatic malignancy in otherwise relatively unremarkable appearing polyps.

Abstract Background Monitored Anesthesia Care (MAC) is an anesthetic service involving the titration of sedatives/analgesics to achieve varying levels of sedation while avoiding general anesthesia (GA) and airway instrumentation. The goal of our study was to determine the overall incidence of conversion from MAC to general anesthesia with airway instrumentation and elucidate reasons and risk factors for conversion. Methods In this retrospective observational study, all non-obstetric adult patients who received MAC from July 2002 to July 2015 at Mount Sinai Hospital were electronically screened for inclusion via a clinical database. Patient, procedure, anesthetic, and practitioner data were all collected and analyzed to generate descriptive analyses. Subsequent univariate and multivariate analyses were used to identify specific risk factors associated with conversion to GA. Results Overall, 0.50% (1097/219,061) of MAC cases were converted to GA. Approximately half of conversions were due to the patient’s “intolerance” of MAC (with or without failed regional anesthesia), while the other half were due to physiologic derangements. Body mass index, male sex, American Society of Anesthesiologists Physical Status Classification, anesthesia team composition, and surgical specialty were all associated with risk of conversion to GA. Conclusions This is one of the first and largest retrospective studies aimed at identifying reasons and risk factors associated with the conversion of MAC to GA. These findings may be used to help better anticipate or prevent these events.

Abstract This paper provides a viewpoint of the culture and subcultures at Google Inc., which is a famous global company, and has a huge engineering staff and many talented leaders. Through its history of development, it has had positive impacts on society; however; there have been management challenges. The Board of Directors (BoDs) developed and implemented a way to measure the abilities of their managers, which helped to identify problems. This paper will analyze the case study of Harvard Business Review, Oxygen Project, and clarify the management problem in Google’s organization. It will also compare Google with Zappos, a much smaller organization, and present how the BoDs of Zappos assesses its culture and subcultures. In this paper, we will recommend eight important points to building an organizational culture that is positive for stable growth of a company. We believe that much of what be learned could be useful to other business leaders, regardless of company scale.

Plasmacytoid dendritic cells (pDCs) are "natural" interferon α (IFNα)-producing cells. Despite their importance to antiviral defense, autoimmunity, and ischemic liver graft injury, because DC subsets are rare and heterogeneous, basic questions about liver pDC function and capacity to make cytokines remain unanswered. Previous investigations failed to consistently detect IFNα mRNA in HCV-infected livers, suggesting that pDCs may be incapable of producing IFNα. We used a combination of molecular, biochemical, cytometric, and high-dimensional techniques to analyze DC frequencies/functions in liver and peripheral blood mononuclear cells (PBMCs) of hepatitis C virus (HCV)-infected patients, to examine correlations between DC function and gene expression of matched whole liver tissue and liver mononuclear cells (LMCs), and to determine if pDCs can produce multiple cytokines. T cells often produce multiple cytokines/chemokines but until recently technical limitations have precluded tests of polyfunctionality in individual pDCs. Mass cytometry (CyTOF) revealed that liver pDCs are the only LMC that produces detectable amounts of IFNα in response TLR-7/8 stimulation. Liver pDCs secreted large quantities of IFNα (~2 million molecules of IFNα/cell/hour) and produced more IFNα than PBMCs after stimulation, p = 0.0001. LMCs secreted >14-fold more IFNα than IFNλ in 4 hours. Liver pDC frequency positively correlated with whole liver expression of "IFNα-response" pathway (R2 = 0.58, p = 0.007) and "monocyte surface" signature (R2 = 0.54, p = 0.01). Mass cytometry revealed that IFNα-producing pDCs were highly polyfunctional; >90% also made 2-4 additional cytokines/chemokines of our test set of 10. Liver BDCA1 DCs, but not BDCA3 DCs, were similarly polyfunctional. pDCs from a healthy liver were also polyfunctional. Our data show that liver pDCs retain the ability to make abundant IFNα during chronic HCV infection and produce many other immune modulators. Polyfunctional liver pDCs are likely to be key drivers of inflammation and immune activation during chronic HCV infection.

Background/AimsTo compare the performance of a modified Glasgow Blatchford score (mGBS) to the Glasgow Blatchford score (GBS) and the pre-endoscopic Rockall score (RS) in predicting clinical interventions in Vietnamese patients with acute nonvariceal upper gastrointestinal bleeding (AN-VUGIB).Methods : A prospective multicenter cohort study was conducted in five tertiary hospitals from May 2013 to February 2014. The mGBS, GBS, and pre-endoscopic RS scores were prospectively calculated for all patients. The accuracy of mGBS was compared with that of GBS and pre-endoscopic RS using area under the receiver operating characteristic curve (AUC). Clinical interventions were defined as blood transfusions, endoscopic or radiological intervention, or surgery.Results : There were 395 patients including 128 (32.4%) needing endoscopic treatment, 117 (29.6%) requiring blood transfusion and two (0.5%) needing surgery. In predicting the need for clinical intervention, the mGBS (AUC, 0.707) performed as well as the GBS (AUC, 0.708; p=0.87) and outperformed the pre-endoscopic RS (AUC, 0.594; p

Wild mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common offender. Patients may complain of nausea, vomiting, diarrhea and/or abdominal pain. If not aggressively treated, fulminant hepatic failure may develop within several days of ingestion. In this case report, a patient poisoned with Amanita bisporigera is described, along with the typical clinical presentation, patient outcomes, and treatment options for dealing with an Amanita mushroom poisoning.

The effects of different inclusion rates of Poncirus trifoliata (PT) extract on in vitro ruminal fermentation parameters were investigated. Six dose levels were referred to as follows: PT0, control (without PT); PT1, (3 mg/L); PT3, (9 mg/L); PT5, (15 mg/L); PT7, (21 mg/L); PT9, (27 mg/L), each incubated with 50 mL of buffered rumen fluid and 300 mg of timothy hay as a substrate for 72 h of incubation using an in vitro batch culture system. The in vitro dry matter digestibility (IVDMD) was significantly affected by the PT dose, except after 6 and 48 h of incubation. Total volatile fatty acids (VFAs) increased quadratically (12 h of incubation) within the range of PT1–PT7, whereas decreased at PT9 dose. Methane (CH4) production and the proportion of CH4 in the total gas produced decreased linearly after 12 h of incubation. The relative abundance of Ruminococcus albus and Ruminoccocus flavefaciens was greater at the doses PT1 than PT0, whereas that of Fibrobacter succinogenes was greater at PT0 than at PT9 after 24 h of incubation. Methanogenic archaea decreased linearly with increasing PT dose after 12 h of incubation. The abundance of ciliate-associated methanogens decreased linearly over 24 h of incubation under PT7 and PT9 treatments. These results suggest that the dose of PT can modulate ruminal fermentation to alter VFA concentration and reduce CH4 production by altering ruminal bacterial abundance.Highlights This study evaluated the dose-response effects of Poncirus trifoliata as a methane mitigation agent in ruminants. Inclusion of Poncirus trifoliate lowered in vitro dry matter digestibility and total volatile fatty acid concentration. Inclusion of Poncirus trifoliata extract reduced methane production after 12 h of incubation but did not maintained. Inclusion of Poncirus trifoliata extract reduced methanogenic archaea and ciliate-associated methanogens abundance

The family Syllidae is the most taxonomically complex of the phylum Annelida. Although the gene order in the phylum Annelida’s mitochondrial DNA (mtDNA) is well conserved, several exceptional cases have been reported. In this study, we describe the mitochondrial genome of a Syllis sp. that is 17,092 bp in length and contains 13 mitochondrial protein-coding genes (PCGs), 23 transfer RNA (tRNA) genes, including two tRNA-M, two ribosomal RNA (rRNA) genes, and a putative control region between tRNA-W and tRNA-G distinguished by a single short noncoding region. However, the gene order is not similar to those of other species in the family Syllidae. Phylogenetic analyses of 18S rRNA and 13 PCGs sequences demonstrated that this worm was clustered with other Syllis species in the family Syllidae. This is the first study to reveal the complete mitochondrial genome sequence of a previously unidentified Syllissp. improving our understanding of the molecular biological characteristics of the poorly known genus Syllis.

In this study, the complete mitochondrial genome of the Rikuzen flounder ( Dexistes rikuzenius) using next-generation sequencing and bioinformatics analysis is presented. The mitogenome was found to be a circular molecule 17,494 bp in length, containing 13 protein-coding genes (PCG), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and one control region (D-loop). Proportional nucleotide composition was A: 28.80% (5,039 bp), T: 26.51% (4,638 bp), C: 28.72% (5,025 bp) and G: 15.96% (2,792 bp), with a combined A+T content of 55.32%. The phylogenetic relationships of the taxon with 19 other flatfish species in the order Pleuronectiformes were then analyzed based on the 13 PCGs. Dexistes rikuzenius was most closely clustered with Cleisthenes herzensteini within this order, suggesting a close relationship.

Cleaning the facade of high-rise buildings is a dangerous task that may cause workplace accidents, such as falls and collisions with the façade. Various technologies and devices have been conceived to address this problem, including a façade cleaning robot guided by built-in rails which was developed in South Korea. In this study, a life cycle cost (LCC) analysis was performed to verify the applicability and commercial feasibility of the robot in question. The LCC analysis results showed that the benefit/cost ratio, rate of return, and annual reduction in façade cleaning costs for the automated method were 1.97, 7.19%, and 49.21%, respectively. Thus, the developed robot was confirmed to provide high economic efficiency for high-rise buildings. In addition, a sensitivity analysis of the results to changes in the values of the main input variables was conducted to verify the reliability of the LCC analysis. The results of this study indicated that commercial application of the robot in consideration should improve the safety of façade cleaning work and have very positive economic, industrial, and societal effects.

Abstract Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0–40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639–2.687; p

BackgroundInfants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age.ResultsNine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious.ConclusionSebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011.

BackgroundIn 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework.Materials and methodsWe undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.ResultsAmong the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20–34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people “not initiating treatment” (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95–3.86). Nine-month isoniazid monotherapy therapy was associated with “not completing treatment,” compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16–1.41).ConclusionAmong participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

BackgroundThis study using multi-center health examination data from Korean adults was conducted to confirm changes in weight, and their related cardiometabolic parameters, before and after strengthening of social distancing regulations.MethodsA retrospective cohort study was conducted using health check-up data from 13 university hospitals. The study period was from January 2018 to July 2020. To examine the effect of systematic social distancing measures, participants who underwent a health check-up (Visit 3) between July 2020 and July 2021 (during full scale social distancing), and had undergone two previous health check-ups (Visits 1 and 2) between January 2018 and June 2020 (before social distancing), were selected. In total, data from 7,875 participants were analyzed. Linear mixed-effect models were used to calculate estimates of anthropometric indices and metabolic markers measured on Visits 2 and 3, compared with measurements from Visit 1.ResultsThere were no significant differences in body weight, body mass index, waist circumference, and body composition on Visit 3 than on Visits 1 and 2. However, the odds of metabolic syndrome and its components, including hypertension, high glucose, diabetes, hypercholesterolemia, hypertriglyceridemia, hyper-non-high-density lipoprotein cholesterolemia, and dyslipidemia were significantly higher on Visit 3 than on Visits 1 and 2. The increase in metabolic complications was marked, particularly in relatively young adults who visited health check-up centers located in the capital area.ConclusionMetabolic syndrome and its components were significantly worse after high level social distancing, although there were no significant increases in anthropometric indices and body fat levels. Healthcare providers need to prevent and manage worsening of metabolic parameters in subpopulations prone to be more sedentary and eat unhealthy food during the COVID-19 pandemic and associated social distancing measures.

Sargassum horneri (SH) is a brown macroalgal species commonly found along the coast of Japan, China, and Korea. SH possesses valuable bioactive compounds that can be developed as functional food ingredients as well as pharmaceutical agents for both humans and animals. In this study, SH was tested for its potential prebiotic effect. Several solvent-assisted extracts of SH were tested on the growth of three species of probiotics (LAB) (Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus brevis) and fish pathogen bacteria (Streptococcus iniae, Streptococcus parauberis, Edwersiella tarda) both in vitro and in vivo. According to the in vitro results, Celluclast extract (SHC) and crude polysaccharide extract (SHCPs) of SH showed outstanding growth enhancing activity in all LAB species and excellent antibacterial activity against pathogenic bacteria dose-dependently. Both SHC and SHCPs induced the production of secondary metabolites from LAB. The secondary metabolites successfully reduced pathogenic bacterial growth. Furthermore, in vivo experiments revealed that co-treatment with LAB and SHC/SHCPs diminished the mortality of Streptococcus parauberis infected zebrafish by modulating iNOS, COX-2 expressions. Similarly, SH act as an anti-inflammatory agent against S. parauberis infection by hindering NF-κB pathway activation. Conclusively, the results achieved from the study suggest that S. horneri has the potential to be used as a prebiotic dietary supplement and possesses a protective effect against S. parauberis infections in the aquaculture industry.

Purpose: Inter-tumoral heterogeneity at the differential lesion level raises the possibility of distinct organ-specific responses to immune checkpoint inhibitors (ICIs). We aimed to comprehensively examine the clinicopathological factors to predict and assess the efficacy of nivolumab, programmed cell death protein 1 (PD-1) blockade at an individual tumor site-specific level in patients with advanced hepatocellular carcinoma (aHCC). Patients and Methods: We enrolled 261 aHCC patients treated with nivolumab between 2012 and 2018. Eighty-one clinicopathological factors were comprehensively collected and analyzed. The association between all variables and survival outcomes was evaluated. According to tumor site, the organ-specific responses were assessed based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Results: The liver was the most commonly involved organ (75.1%), followed by the lungs (37.5%) and lymph nodes (LNs, 11.5%). The liver of nonresponders was more frequently the organ of progression, while the lungs of responders were more frequently the organs of response. Among the 455 individual lesions (liver, n = 248; lung, n = 124; LN, n = 35; others including bone or soft tissues, n = 48), intrahepatic tumors showed the least response (10.1%), followed by lung (24.2%) and LN tumors (37.1%), indicating the presence of distinct organ-specific responses to nivolumab. In intrahepatic tumors, the organ-specific response rate decreased as the size increased (13% for ⩽50 mm, 8.1% for 50–100 mm, and 5.5% for >100 mm). In the subgroup analysis according to tumor location, patients with lung only metastasis (⩾30 mm) showed the best progression-free survival (PFS) and overall survival (OS). In contrast, primary HCC (⩾100 mm) without lung metastasis had the worst PFS and OS. Comprehensive analyses also revealed that liver function and systemic inflammatory indices, such as neutrophil-to-lymphocyte ratio (NLR), were significantly associated with PFS and OS. Conclusion: The presence and size of liver tumors, liver function, and NLR are key factors determining the response to nivolumab in aHCC. These clinical factors should be considered when treating patients with advanced HCC with PD-1 blockade.

Biomonitoring of workers is an approach of evaluating workers’ exposure to chemicals and particulate matter by measuring biomarkers of parent chemicals, their metabolites, and reaction products in workers’ biospecimens. Prerequisites for biological monitoring in the workplace include permission to enter the workplace, approval of the study plan from the IRB (Institutional Review Board), and obtaining consent from workers. Because of the complex legal process involved in biomonitoring, few studies have been conducted so far on biomonitoring of workers’ exposures to nanoparticles and other hazards from emerging materials and advanced nanotechnologies. We have developed a cell-based biomonitoring device that can evaluate acute cytotoxicity and various other effect biomakers, such as inflammation, at realistic workplace exposure. This device is based on air–liquid interphase (ALI) and can be used to evaluate cell toxicity and early effect biomarkers along adverse outcome pathways. Following exposure of A549 lung epithelial cells in ALI to workplace air for 1–2 h, the cells were processed to assess the induction of inflammatory and cell damage biomarkers. Initially, we estimated the deposition rate of nanoparticles in the transwell by exposing the cell-free ALI device to silver nanoparticle aerosols (AgNP 20–30 nm) for 2 h in the laboratory. Then A549 lung epithelial cells cultured on the transwell in the ALI device were exposed to AgNP nanoaerosols for 2 h and evaluated for cytotoxicity and induction of mRNAs of pro-inflammatory cytokines IL-1b, IL-6, and TNF-α. Then the cells in the ALI device were exposed to 3-D printer emissions at the workplace and evaluated for the same matched endpoints. The mRNA levels for IL-1b, IL-6, and TNF-α increased significantly at the end of 2-h exposure of A549 cells to the positive control AgNP aerosols. These mRNAs, as well as LDH and microprotein concentrations, increased even more after 24-h post-exposure incubation (p < 0.05). Cytotoxicity evaluation of 3-D printer emissions at 810 and 957 μg/m3, which was more than 80 times higher than the airborne total suspended particulate concentrations in the workplace air (9–12.5 μg/m3), suggested no significant acute cytotoxicity at the end of 2-h exposure to 3-D-printing emission, as well as at 24-h post-exposure incubation. Hyperspectral microscopic observation showed that 3-D printers emitted particles to be attached to A549 cells after 2-h exposure, and many particles were internalized by A549 cells after 24 h of post-exposure incubation. The mRNA expression of pro-inflammatory cytokine IL-1b and IL-6 increased significantly after 2-h exposure to 3-D printer emissions and after 24-h incubation (only IL-6). In contrast, the expression of TNF-α mRNA decreased significantly after 2 h of exposure to 3-D printers and decreased even more after 24-h post-exposure incubation. These results support the use of cell-based ALI devices for direct assessment of airborne hazards in the workplace, for probing toxicological properties of airborne contaminants using adverse molecular pathways, and for guiding study design for workplace biomonitoring. ALI devices can bridge conventional exposure assessment with cellular toxicity testing platforms for hazard and risk assessment.

Abstract Purpose Intra-articular injection of hyaluronic acid (HA) has shown promises in reducing pain and improving physical function in knee osteoarthritis (OA). Recently, cell-based therapies using mesenchymal stem cells (MSCs) have emerged as potential treatments. However, few studies have compared the treatment outcomes between MSCs and HA. This study aimed to compare the clinical and radiological outcomes of intra-articular injections of MSCs versus HA in patients with knee OA. Methods A cohort of 209 patients with knee OA were retrospectively screened for those who underwent intra-articular injections using MSCs or HA. Thirty MSC-treated patients (MSC group) were pair-matched with thirty HA-treated patients (HA group) based on gender and age. Clinical outcomes were evaluated using the visual analog scale (VAS), International Knee Documentation Committee (IKDC) rating system, and Lysholm scoring system. Radiological evaluation was assessed using the Kellgren-Lawrence (K-L) grading system. Results MSC treatment yielded consistent significant improvements in VAS, IKDC and Lysholm scores. In the HA group, VAS scores significantly decreased at 1 month, slightly increased at 3 months, and increased significantly from 3 months to 1 year after injection. The IKDC and Lysholm scores improved significantly until 3 months, but gradually worsened thereafter. Significantly greater improvements in VAS (P = 0.041), IKDC (P = 0.014), and Lysholm (P = 0.020) scores were observed in the MSC group compared to those in the HA group at 1-year post-treatment. The K-L grade worsened in a few patients, especially those in the HA group, albeit no significant difference. Conclusions MSC group showed better VAS, IKDC, and Lysholm scores at 1-year post-treatment, compared to the HA group, although earlier clinical improvements were superior in the HA group for the initial 3 months. Level of Evidence Therapeutic study, Level III.

Abstract Background The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. Methods Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed. Results Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. Conclusions The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.

Mirror neuron system can be activated by observation and execution of an action. It has an important function of action understanding. We investigated brain activations in humans by observing the strength of a hand grasp using functional magnetic resonance imaging. Twenty right-handed healthy individuals, consisting of 10 males and 10 females, aged 22.40 ± 2.04 years, were recruited into this study from September to November 2017 via posters. Light hand grasp task video showed a hand lightly grasping and releasing a ball repeatedly. Powerful hand grasp task video showed a hand tightly grasping and releasing a ball repeatedly. Functional magnetic resonance imaging block design paradigm comprised five stimulation blocks alternating with five baseline blocks. Stimulation blocks were presented with two stimulus tasks, consisting of a light grasp and a powerful grasp. Region of interest was defined around the inferior parietal lobule, inferior frontal gyrus, and superior temporal sulcus which have been called mirror neuron system. The inferior parietal lobule, fusiform, postcentral, occipital, temporal, and frontal gyri were activated during light and powerful grasp tasks. The BOLD signal response of a powerful grasp was stronger than that of a light grasp. These results suggest that brain activation of the inferior parietal lobule, which is the core brain region of the mirror neuron system, was stronger in the powerful grasp task than in the light grasp task. We believe that our results might be helpful for instructing rehabilitation of brain injury. This study was approved by the Institutional Review Board of Daegu Oriental Hospital of Daegu Haany University on September 8, 2017 (approval No. DHUMC-D-17020-PRO-01).

Background Mastectomy flap necrosis is a common and challenging complication of direct-to-implant (DTI) breast reconstruction. The PICO single-use negative-pressure wound therapy device may reduce the complications associated with skin flap necrosis. We evaluated the relationship between PICO use and the incidence of mild, moderate, and severe skin flap necrosis in patients at high risk of necrosis. Methods Using medical records from January 2015 to March 2019, we retrospectively analyzed patients who underwent DTI breast reconstruction after oncological breast surgery at a single institution and identified those at high risk for skin flap necrosis. During this period, PICO was used selectively for patients deemed to be at particularly high risk. Patient demographics, operative characteristics, and the degree of skin flap necrosis were compared according to whether PICO was used. Results Of 117 patients (122 breasts), 45 were deemed to be at high risk of skin flap necrosis. PICO was applied to 38 of these breasts, and seven breasts received a conventional dressing. Skin flap necrosis occurred in 30 breasts (24 in the PICO group [63.2%] vs. 6 in the no-PICO group [85.7%]). Significantly fewer cases of severe skin flap necrosis were observed in the PICO group (2/38 [5.3%]) than in the no-PICO group (3/7 [42.9%]) (P=0.004). There were no significant between-group differences in outcomes measured using BREAST-Q scores. Conclusions Use of a single-use negative-pressure wound therapy device can reduce the risk of severe skin flap necrosis in patients at high risk of skin flap complications associated with DTI breast reconstruction.

Background Acute gastrointestinal (GI) bleeding is not an uncommon complication of oral anticoagulation (OAC) therapy that requires medication cessation. However, drug cessation may cause fatal stroke or systemic embolization in patients at high thromboembolic risk. Here we sought to find an appropriate anticoagulation cessation strategy in cases of GI bleeding during OAC therapy. Methods This single-center retrospective cohort analysis was performed between 2010 and 2018. Patients were enrolled if the following three consecutive conditions were met: 1) electrocardiography electrocardiography-proven atrial fibrillation; 2) OAC therapy; and 3) GI bleeding. We divided the drug cessation strategy into the continuation and discontinuation groups. During 1-year follow-up, the rates of major thromboembolic and rebleeding events were calculated. Results One hundred and forty-six patients (continuation [n = 54] vs. discontinuation [n = 92] group) were enrolled. Patients in the discontinuation group were more likely to be older (69.8 ± 9.0 yrs vs. 74.9 ± 8.9 yrs, p = 0.001), while patients in the continuation group were more likely to have undergone cardiac valve surgery (51.9% vs. 20.7%, pConclusion No single risk factor or drug cessation strategy was attributed to adverse clinical events after GI bleeding. The risk of future thrombotic or rebleeding events should be individualized and controlled for based on a pre-existing stratification system.

In 2018, the World Health Organization recommended a 6-month four-drug regimen (rifampicin, ethambutol, pyrazinamide, and levofloxacin) for the treatment of isoniazid-monoresistant tuberculosis. However, the regimen had very low certainty. This cohort study assessed the impact of fluoroquinolone use and initial baseline regimen on treatment effectiveness in isoniazid-monoresistant tuberculosis. This multicenter retrospective cohort study included 318 patients with isoniazid-monoresistant tuberculosis notified between 2011 and 2018 in Korea. Baseline regimens were classified into two groups, namely 6-9-month rifampicin, ethambutol, and pyrazinamide (6-9REZ) and a combination regimen of 2-month rifampicin, ethambutol, pyrazinamide and 7-10-month rifampicin and ethambutol (2REZ/7-10RE). Multivariable logistic regression was performed to assess factors associated with positive treatment outcomes. Of 318 enrolled patients, 234 (73.6%) were treated with the 6-9REZ and 103 (32.4%) with additional fluoroquinolone. In a multivariable logistic regression model comparing the 6-9REZ and 2REZ/7-10RE groups, there was no difference in the odds of positive outcomes (adjusted odds ratio = 1.08, 95% confidence interval = 0.65-1.82). Addition use of fluoroquinolone was not associated with positive treatment outcomes in the whole cohort (adjusted odds ratio = 1.41, 95% confidence interval = 0.87-2.27); however, its additional use was beneficial in the 2REZ/7-10RE subgroup (adjusted odds ratio = 3.58, 95% confidence interval = 1.32-9.75). Both initial baseline regimens, 6-9REZ and 2REZ/7-10RE, were similarly effective. Shortening of the pyrazinamide administration duration with additional fluoroquinolone use could be a safe alternative for patients with potential hepatotoxicity related to pyrazinamide.

In the transition zone of railway tracks, track irregularities occur frequently due to differential settlement, which arises from the difference between the vertical supporting stiffness of the abutment and the backfill. This is disadvantageous because it increases the maintenance requirements and deteriorates the ride quality. To address this challenge, this study proposes a strategy involving the application of cement-treated gravel reinforced with geogrids and rigid facing walls. The reinforced subgrade for railways (RSR), which can reduce residual settlement through the initial construction of the backfill reinforced with geogrids and the subsequent development of the rigid facing wall, was constructed at the transition zone with cement-treated gravel as the backfill material. The long-term behaviors during and after construction on the RSR for a period of 16 months were evaluated by analyzing the surface and ground settlements, horizontal earth pressure, and geogrid strain. The minor net settlement of the reinforced backfill converges at the early stage of subgrade construction, and the horizontal earth pressure was approximately reduced to the level of 54–63% of the Rankine active earth pressure.

Introduction: Blood pressure is closely linked with immune function. This study examined the association between natural killer (NK) cell activity (NKA) and blood pressure and the development of hypertension according to NKA levels. Methods: This study enrolled 1543 adults who underwent NKA measurement and serial health check-ups at a medical center in Korea. NKA was estimated as the concentration of IFN-g in the incubated whole blood containing a patented stimulatory cytokine. The participants were categorized into quartiles according to their NKA levels. Participants without hypertension were followed up, and the development of hypertension was compared according to the quartiles. Results: The prevalence of hypertension was not different among the NKA quartiles, whereas blood pressures significantly decreased, followed by an increment of quartiles (systolic blood pressure of 119.0 in Q1 and 117.0 in Q4, P-trend = 0.018). Over a mean follow-up period of 2.13 years, hypertension developed in 156 of 1170 individuals without baseline hypertension. The hazard ratio of Q4 compared with Q1 was 0.625 (95% CI: 0.397-0.983; p = 0.042). Conclusion: In conclusion, our findings indicate a correlation between lower NKA and higher blood pressure and the development of incident hypertension. This may suggest a potential protective role of NK cells against endothelial dysfunction. Further research is necessary to elucidate the specific relationship between immune functions and endothelial function. [ABSTRACT FROM AUTHOR]

Abstract Background This study evaluated the influence of meniscal allograft transplantation (MAT) on knee joint mechanics during normal walking using finite element (FE) analysis and biomechanical data. Methods The study included 20 patients in a transpatellar group and 25 patients in a parapatellar group. Patients underwent magnetic resonance imaging (MRI) evaluation after lateral MAT as a baseline input for three-dimensional (3D) and FE analyses. Three different models were compared for lateral MAT: intact, transpatellar approach, and parapatellar approach. Analysis was performed using high kinematic displacement and rotation inputs based on the kinematics of natural knees. ISO standards were used for axial load and flexion. Maximum contact stress on the grafted menisci and maximum shear stress on the articular surface of the knee joint were evaluated with FE analysis. Results Relatively high maximum contact stresses and maximum shear stresses were predicted in the medial meniscus and cartilage of the knee joint during the loading response for all three knee joint models. Maximum contact stress and maximum shear stress in the meniscus and cartilage increased on the lateral side after lateral MAT, especially during the first 20% of the stance phase of the gait cycle. The transpatellar approach was most similar to the intact knee model in terms of contact stresses of the lateral grafted and medial meniscus, as well as maximum shear stresses during the gait cycle. In addition, the transpatellar model had lower maximum contact stress on the menisci than did the parapatellar model, and it also had lower maximum shear stress on the tibial cartilage. Conclusions Therefore, the transpatellar approach may reduce the overall risk of degenerative osteoarthritis (OA) after lateral MAT.

Ruminants produce large amounts of methane as part of their normal digestive processes. Recently, feed additives were shown to inhibit the microorganisms that produce methane in the rumen, consequently reducing methane emissions. The objective of this study was to evaluate the dose–response effect of Phyllostachys nigra var. henonis (PHN) and Sasa borealis supplementation on in vitro rumen fermentation, methane, and carbon dioxide production, and the microbial population. An in vitro batch culture system was used, incubated without bamboo leaves (control) or with bamboo leaves (0.3, 0.6, and 0.9 g/L). After 48 h, total gas, methane, and carbon dioxide production decreased linearly with an increasing dose of bamboo leaves supplementation. The total volatile fatty acid, acetate, and acetate-to-propionate ratio were affected quadratically with increasing doses of bamboo leaves supplementation. In addition, propionate decreased linearly. Butyrate was increased linearly with increasing doses of PHN supplementation. The absolute values of total bacteria and methanogenic archaea decreased linearly and quadratically with an increasing dose of PHN treatment after 48 h. These results show that bamboo leaves supplementation can reduce methane production by directly affecting methanogenic archaea, depressing the metabolism of methanogenic microbes, or transforming the composition of the methanogenic community. These results need to be validated using in vivo feeding trials before implementation.

Multi-functionalized carbon nanomaterials have attracted interest owing to their excellent synergic properties, such as plasmon resonance energy transfer and surface-enhanced Raman scattering. Particularly, nanoparticle (NP)-decorated graphene (GRP) has been applied in various fields. In this study, silver NP (AgNP)- and magnetic iron oxide NP (IONP)-decorated GRP were prepared and utilized as biosensing platforms. In this case, AgNPs and GRP exhibit plasmonic properties, whereas IONPs exhibit magnetic properties; therefore, this hybrid nanomaterial could function as a magnetoplasmonic substrate for the magnetofluoro-immunosensing (MFI) system. Conversely, exosomes were recently considered high-potential biomarkers for the diagnosis of diseases. However, exosome diagnostic use requires complex isolation and purification methods. Nevertheless, we successfully detected a prostate-cancer-cell-derived exosome (PC-exosome) from non-purified exosomes in a culture media sample using Ag/IO-GRP and dye-tetraspanin antibodies (Ab). First, the anti-prostate-specific antigen was immobilized on the Ag/IO-GRP and it could isolate the PC-exosome from the sample via an external magnetic force. Dye-tetraspanin Ab was added to the sample to induce the sandwich structure. Based on the number of exosomes, the fluorescence intensity from the dye varied and the system exhibited highly sensitive and selective performance. Consequently, these hybrid materials exhibited excellent potential for biosensing platforms.

In areas where it is difficult to secure additional land for railways, a plan to increase rail transport capacity by widening existing embankments is required. When widening the embankment, additional stress is generated at the bottom of the existing embankment, resulting in an additional settlement (interlocking settlement) of the existing embankment. Reinforced subgrade for railways (RSR) is an efficient method for widening embankments without additional sites. In this study, an existing railway embankment in operation was widened using the RSR, with the interlocking settlement evaluated and analyzed during and after construction. Results show that a widened embankment using RSR can secure train operation stability on existing tracks, even in ground conditions including shallow soft layers. The interlocking settlement was mainly affected by the backfill load and hardly affected by the wall load of the RSR. In addition, it was confirmed that the interlocking settlement mainly occurred in the backfill construction and stabilization period of RSR construction and converged early.

In this research, a heartbeat classification method is presented based on evolutionary feature optimization using differential evolution (DE) and classification using a probabilistic neural network (PNN) to discriminate between normal and arrhythmic heartbeats. The proposed method follows four steps: (1) preprocessing, (2) heartbeat segmentation, (3) DE feature optimization, and (4) PNN classification. In this method, we have employed direct signal amplitude points constituting the heartbeat acquired from the ECG holter device with no secondary feature extraction step usually used in case of hand-crafted, frequency transformation or other features. The heartbeat types include normal, left bundle branch block, right bundle branch block, premature ventricular contraction, atrial premature, ventricular escape, ventricular flutter and paced beat. Using ECG records from the MIT-BIH, heartbeats are identified to start at 250 ms before and end at 450 ms after the respective R-peak positions. In the next step, the DE method is applied to reduce and optimize the direct heartbeat features. Although complex and highly computational ECG heartbeat classification algorithms have been proposed in the literature, they failed to achieve high performance in detecting some minority heartbeat categories, especially for imbalanced datasets. To overcome this challenge, we propose an optimization step for the deep CNN model using a novel classification metric called the Matthews correlation coefficient (MCC). This function focuses on arrhythmia (minority) heartbeat classes by increasing their importance. Maximum MCC is used as a fitness function to identify the optimum combination of features for the uncorrelated and non-uniformly distributed eight beat class samples. The proposed DE-PNN scheme can provide better classification accuracy considering 8 classes with only 36 features optimized from a 253 element feature set implying an 85.77% reduction in direct amplitude features. Our proposed method achieved overall 99.33% accuracy, 94.56% F1, 93.84% sensitivity, and 99.21% specificity.

Concomitant with the recent advances in deep learning, automatic speech recognition and visual speech recognition (VSR) have received considerable attention. However, although VSR systems must identify speech from both frontal and profile faces in real-world scenarios, most VSR studies have focused solely on frontal face pictures. To address this issue, we propose an end-to-end sentence-level multi-view VSR architecture for faces captured from four different perspectives (frontal, 30°, 45°, and 60°). The encoder uses multiple convolutional neural networks with a spatial attention module to detect minor changes in the mouth patterns of similarly pronounced words, and the decoder uses cascaded local self-attention connectionist temporal classification to collect the details of local contextual information in the immediate vicinity, which results in a substantial performance boost and speedy convergence. To compare the performance of the proposed model for experiments on the OuluVS2 dataset, the dataset was divided into four different perspectives, and the obtained performance improvement was 3.31% (0°), 4.79% (30°), 5.51% (45°), 6.18% (60°), and 4.95% (mean), respectively, compared with the existing state-of-the-art performance, and the average performance improved by 9.1% compared with the baseline. Thus, the suggested design enhances the performance of multi-view VSR and boosts its usefulness in real-world applications.

The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of urine organic acid metabolites in participants with hepatic steatosis and fibrosis in nonalcoholic Korean adults. Hepatic steatosis and fibrosis, in 68 men and 65 women, were evaluated using quantification by proton density fat fraction with magnetic resonance (MR) imaging and MR elastography, respectively. Urine metabolites were obtained using a high-performance liquid chromatography–mass spectrometry analysis. The candidate metabolites were included in the logistic regression models for hepatic steatosis and fibrosis. The association between high p-hydroxyphenyllactate levels and hepatic steatosis was not independent of body mass index and Homeostatic Model Assessment-insulin resistance. High ethylmalonate, β-hydroxybutyrate, and sulfate levels were significantly related to a low probability of hepatic fibrosis, independent of covariates. In conclusion, urine metabolites were not related to hepatic steatosis independent of obesity and insulin resistance, while several metabolites were specifically associated with hepatic fibrosis. Further study is required to verify the diagnostic value of the metabolites in a population with wide-spectrum NAFLD.

Skeleton data, which is often used in the HCI field, is a data structure that can efficiently express human poses and gestures because it consists of 3D positions of joints. The advancement of RGB-D sensors, such as Kinect sensors, enabled the easy capture of skeleton data from depth or RGB images. However, when tracking a target with a single sensor, there is an occlusion problem causing the quality of invisible joints to be randomly degraded. As a result, multiple sensors should be used to reliably track a target in all directions over a wide range. In this paper, we proposed a new method for combining multiple inaccurate skeleton data sets obtained from multiple sensors that capture a target from different angles into a single accurate skeleton data. The proposed algorithm uses density-based spatial clustering of applications with noise (DBSCAN) to prevent noise-added inaccurate joint candidates from participating in the merging process. After merging with the inlier candidates, we used Kalman filter to denoise the tremble error of the joint’s movement. We evaluated the proposed algorithm’s performance using the best view as the ground truth. In addition, the results of different sizes for the DBSCAN searching area were analyzed. By applying the proposed algorithm, the joint position accuracy of the merged skeleton improved as the number of sensors increased. Furthermore, highest performance was shown when the searching area of DBSCAN was 10 cm.

Deep learning technology has encouraged research on noise-robust automatic speech recognition (ASR). The combination of cloud computing technologies and artificial intelligence has significantly improved the performance of open cloud-based speech recognition application programming interfaces (OCSR APIs). Noise-robust ASRs for application in different environments are being developed. This study proposes noise-robust OCSR APIs based on an end-to-end lip-reading architecture for practical applications in various environments. Several OCSR APIs, including Google, Microsoft, Amazon, and Naver, were evaluated using the Google Voice Command Dataset v2 to obtain the optimum performance. Based on performance, the Microsoft API was integrated with Google’s trained word2vec model to enhance the keywords with more complete semantic information. The extracted word vector was integrated with the proposed lip-reading architecture for audio-visual speech recognition. Three forms of convolutional neural networks (3D CNN, 3D dense connection CNN, and multilayer 3D CNN) were used in the proposed lip-reading architecture. Vectors extracted from API and vision were classified after concatenation. The proposed architecture enhanced the OCSR API average accuracy rate by 14.42% using standard ASR evaluation measures along with the signal-to-noise ratio. The proposed model exhibits improved performance in various noise settings, increasing the dependability of OCSR APIs for practical applications.