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Abstract The route of oncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity. Oral reovirus treatment shows no gross toxicities and effectively suppresses multifocal tumor lesions. Orally administered reovirus interacts with the host immune system in the Peyer’s patch of the terminal ileum, increases IgA+ antibody-secreting cells in the lamina propria through MAdCAM-1+ blood vessels, and reshapes the gut microbiome. Oral reovirus promotes antigen presentation, type I/II interferons, and T cell activation within distant tumors, but does not reach or directly infect tumor cells beyond the gastrointestinal tract. In contrast to intratumoral reovirus injection, the presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are indispensable for orally administered reovirus-induced antitumor immunity. Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.

Objectives Smoking remains the leading cause of preventable disease. However, smokers have shown poor compliance with smoking cessation clinics. Smartphone applications present a promising opportunity to improve this compliance. This study aimed to explore the relationship between nicotine dependence, smartphone usage patterns, and anticipated compliance with a smoking cessation application among smokers, with the goal of informing future development of such applications. Methods A total of 53 current smokers were surveyed using a questionnaire. Nicotine dependence was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Variables included the number of hours spent using a phone, willingness to quit smoking, number of previous quit attempts, desired number of text messages about smoking cessation, expected duration of application usage, and FTND scores. Kendall’s partial correlation, adjusted for age, was employed for the analysis. Results The amount of time smokers spent on their mobile devices was negatively correlated with the number of smoking cessation text messages they wanted to receive (τ coefficient = −0.210, p = 0.026) and the duration they intended to use the cessation application (τ coefficient = −0.260, p = 0.006). Conversely, the number of desired text messages was positively correlated with the intended duration of application usage (τ coefficient = 0.366, p = 0.00012). Conclusions Smokers who spent more time on their mobile devices tended to prefer using the cessation application for shorter periods, whereas those who desired more text messages about smoking cessation were more inclined to use the application for longer durations.

In this study, Al joint systems without heat-affected zones (HAZ) were developed on Al/Fe alloy lap joints fabricated by resistance element welding (REW). The robustness of the joints with and without HAZs was quantitatively evaluated to consider another side effect in REW Al/Fe alloy systems. Compared to conventional REW, removing the Al HAZ not only alters the steel properties, but also reduces the work hardening of the Al alloy due to the difference in the distinct heat transfer paths. Furthermore, the presence of Al HAZ significantly influenced the hardness characteristics of the molten steel portion. In the cold wall configuration without Al HAZ, hardness values exceeding those of the hot wall by approximately 100 Hv or more were observed. At a welding current of 10.5 kA, the hot wall configuration demonstrated an approximate 30 % increase in tensile shear load and a 66 % increase in displacement compared to the cold wall configuration without HAZ. In the cold wall conditions, interfacial failure (IF) was not attributed to microstructural disparities but was linked to the formation of an inherent notch root when S20C melted due to the absence of Al HAZ. Contrary to previous reports, the presence of HAZ in Al alloys results the production of tough steel through REW.

This paper addresses the problem of computing the optimal stacking of two monotone polytopes P and Q in Rd. A monotone polytope in Rd is defined as a polytope whose intersection with any line parallel to the last coordinate axis xd is connected, and the stacking of P and Q is defined as a translation of Q, such that “Q touches P from above”. To evaluate the stack, we use three different scoring criteria: (1) the height of the stack, (2) the maximum pointwise distance along the xd-axis, and (3) the volume between P and Q. We propose exact algorithms to compute the optimal stacking for each scoring criterion.

This study proposes an effective repair technology using arc additive manufacturing for pressurized water reactors (PWRs) in nuclear power plants (NPP) aimed at avoiding complete replacements and post-weld-heat treatments (PWHTs) of component parts while ensuring safety and reliability. Effective repair technology is defined as economic and process efficiency, because of maintenance costs and radiation exposure, and it is critical in related industries. The technology is designed to relieve the hardness and martensite fraction of the welding heat affected zone (HAZ) of low alloy steels (SA508) in PWRs penetration/nozzles by heat source generated in the WAAM process, thus ensuring structural integrity. In the first layer of wire arc additive manufacturing processes, 89.6% of the martensite phase was formed in the HAZ of SA508, which was significantly reduced to 45.7% due to repetitive thermal behaviors at the third layer. The resulting process dramatically reduced hardness from 450Hv in the initial layer additive manufacturing to 320Hv in 3 layers without additional heat treatments. Moreover, the study quantitatively investigated the martensite starting temperature (Ms) and bainite starting temperature (Bs) and analyzed the microstructure and mechanical behavior of the developed process using thermodynamic calculation (CALPHAD), finite element method (FEM) simulation, and microstructure quantitative analysis by electron backs-catter diffraction (EBSD). The proposed technologies and their quantitative analysis results can be a substantial alternative to the repair technology for penetration/nozzles in nuclear primary water cooling reactor applications, complying with ASME Sec.IX Qw-462.12 and ISO 15614-1.

ABSTRACTAntiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.

This study focuses on the fatigue fracture response and microstructure behavior of a resistance element weld (REW) in assembling AZ31B magnesium alloy and dual phase (DP) 780 plates. With the increase of the welding current the prior austenite grain size (PAGS) increased, which resulted in a decrease in the fraction of an alpha prime martensite at the welding interface and had little influence on the dual phase at the welding interface. It is clear that the formation of a suitable hook accompanied by the phase transformation between S20C elements and DP780 steels at the interface can have a positive effect on the mechanical properties. However, the Mg melting and the formation of a partially melted zone (PMZ) affected the elongation decrease significantly. Furthermore, the insufficient penetrations of the welding interface, the severe melted Mg and the formation of porosities in the PMZ were fatal to the strength and fatigue performance. Morphologies and microstructure characteristics including phases of the REWed joint were quantitatively analyzed by electron back-scatter diffraction (EBSD) and thermodynamic calculation by coupling the phase diagrams (CALPHAD) method, respectively. The experiment results were incorporated into the finite element method (FEM) to numerically elucidate their effects against mechanical responses including fatigue behaviors. The results explained why the mechanical strength, fatigue endurance, and fracture modes are radically different for joint morphologies and microstructure developments.

Abstract Pulmonary fibrosis (PF) is a fatal chronic disease characterized by accumulation of extracellular matrix and thickening of the alveolar wall, ultimately leading to respiratory failure. PF is thought to be initiated by the dysfunction and aberrant activation of a variety of cell types in the lung. In particular, several studies have demonstrated that macrophages play a pivotal role in the development and progression of PF through secretion of inflammatory cytokines, growth factors, and chemokines, suggesting that they could be an alternative therapeutic source as well as therapeutic target for PF. In this review, we describe the characteristics, functions, and origins of subsets of macrophages involved in PF and summarize current data on the generation and therapeutic application of macrophages derived from pluripotent stem cells for the treatment of fibrotic diseases. Additionally, we discuss the use of macrophage-derived exosomes to repair fibrotic lung tissue.

The present study investigates a fatigue property and its microstructural and interface geometrical effect on the resistance element welded (REWed) aluminum (Al)/high-strength steel (Fe) lap joint. The assembled Al/Fe joints were subjected under the fatigue strength up to 80% of tensile-shear loads with 0.1 of the load ratio. As a result, an exceptional fatigue strength has been secured inducing the base material fracture because there are no noticeable interfacial defects at the 10.5 kA welding condition compared to assemblies joined with 3.5–4.5 kA of welding currents. Even, maximum tensile-shear loads exceed 9 kN at the 10.5 kA welding condition. Microstructural developments of base materials and welding interfaces were thoroughly analyzed by an optical microscopy (OM) and electron backscatter diffraction (EBSD), the development of prior-austenite-grain-boundaries (PAGBs) and α'-martensite phases were observed in the welding interfaces at all conditions. Heat affected zone (HAZ) developments of AA5052 were quantitatively analyzed in terms of recrystallization and grain growth, providing significant differences in the fatigue performances and striation, crack propagation developments. In addition, with the help of a finite element (FE) computational modeling, a mechanical stress distribution and strain behavior by geometries of the joining interface are discussed in detail.

Hybrid precoding has a great potential to achieve near-optimal performance with few radio-frequency (RF) chains in comparison to the number of antennas. This paper proposes a novel hybrid beamforming solution for sum rate maximization in a wideband multi-user multi-input multi-output (MU-MIMO) relay system. The problem at hand is non-convex and hence mathematically intractable due to the constant modulus constraints associated with the analog beamforming design at communicating nodes shared by all sub-carriers. Furthermore, relaying in MU-MIMO systems under frequency-selective channels is also a challenging task as it requires complicated signal processing. To address this problem, source analog beamformer, relay RF combiner and phase-only processing component at each destination are obtained by deriving the common RF processing matrix which enables beamforming gain over all sub-carriers. This process involves reconstruction loss minimization for designing the required analog beamforming vectors having ability to maximize end-to-end signal-to-interference plus noise ratio (SINR). The relay analog precoder is designed by maximizing the received power at each destination through gain maximization of the equivalent baseband channel over the allocated frequency spectrum. To reduce the computational complexity of the iterative approach used to find the relay RF precoding matrix, the closed form expression is derived for achieving the desired objective. Finally, digital baseband processing components are obtained from the equivalent baseband channels by suppressing the interference among transmitted signals indirectly. Simulation results for different system configurations reveal that the proposed algorithm can achieve near-optimal performance.

This paper proposes a novel remote monitoring system using a head mounted display (HMD). By using an HMD, a high degree of immersion and the sense of reality is provided to the user. Further, it becomes more convenient to move the camera position while controlling the robot arm on which the camera is mounted through the coordinates obtained from the HMD sensors. The proposed system performs two tasks. Initially, in order to render images in the HMD, the camera captures input images, and the PC connected to the robot arm sends the image to the PC connected to the HMD in real-time after which the image is rendered in the HMD. For the real-time monitoring, we increased the frame per second by reducing the data size. In order to reduce the data size, we define region of interest which is the region a user can see. Then, region of interest of the image is cropped and the resolution of entire image is degraded. Therefore, two images composed of cropped image and degraded image are transmitted and merged into an image. In this way, we can reduce the data size and provide the user with monitoring the image of the original quality. Next, using the inertial measurement unit sensor and base station sensors built into the HMD, the user controls the displacement of the camera during rotation and translation by controlling the robot arm by the user's own motion. The PC connected to the HMD transmits the motion coordinates of the HMD acquired from the sensor into the PC connected to the robot arm. To control the translation of the camera, we define a coordinate system that represents the y-axis as running from top to bottom, and the x-axis as running from the front to the back in three-dimensional space. Thus, each step motor along each axis, which controls the robot arm, has its movement controlled by supplying appropriate values of angular degrees. Through the above process, the proposed method implements a remote monitoring system with five degrees of freedom. In the experiment, we measured the data transmission delay time and the displacement error due to the robot arm's motion control to determine whether the system is suitable for a real-time remote monitoring system. Experimental results show that the proposed system can be optimally operated with a frame rate of 15 frames per second and a group of pixel resolutions of $640\times 640$ of the cropped image and $240\times 120$ of the degraded image. In addition, the average error rate of the robot arm's displacement was 6.45% when the camera position was controlled through the robot arm.

ObjectivesForeign patients are more likely to receive inappropriate health service in the emergency room. This study aimed to investigate whether there is health inequality between foreigners and natives who visited emergency rooms with injuries and to examine its causes. MethodsWe analyzed clinical data from the National Emergency Department Information System database associated with patients of all age groups visiting the emergency room from 2013 to 2015. We analyzed data regarding mortality, intensive care unit admission, emergency operation, severity, area, and transfer ratio.ResultsA total of 4,464,603 cases of injured patients were included, of whom 67,683 were foreign. Injury cases per 100,000 population per year were 2,960.5 for native patients and 1,659.8 for foreign patients. Foreigners were more likely to have no insurance (3.1% vs. 32.0%, p < 0.001). Serious outcomes (intensive care unit admission, emergency operation, or death) were more frequent among foreigners. In rural areas, the difference between serious outcomes for foreigners compared to natives was greater (3.7% for natives vs. 5.0% for foreigners, p < 0.001). The adjusted odds ratio for serious outcomes for foreign nationals was 1.412 (95% confidence interval [CI], 1.336–1.492), and that for lack of insurance was 1.354 (95% CI, 1.314–1.394).ConclusionsInjured foreigners might more frequently suffer serious outcomes, and health inequality was greater in rural areas than in urban areas. Foreign nationality itself and lack of insurance could adversely affect medical outcomes.

Background Peritoneal carcinomatosis is a fatal clinical presentation of colon cancer, characterized by unresponsiveness to conventional anticancer therapies, including immune checkpoint inhibitors. Here, we elucidated the immune-evasion mechanisms during the peritoneal carcinomatosis of colon cancer and developed a novel immunotherapy by activating the stimulator of interferon genes (STING) pathway.Methods We generated a syngeneic peritoneal carcinomatosis model of colon cancer. Mice were intraperitoneally treated with either STING agonist (MIW815, also known as ADU-S100) or PD-1 blockade or both. The tumor microenvironment was comprehensively analyzed using multiplexed immunofluorescence imaging, flow cytometry, and NanoString immune profiling.Results Intraperitoneal colon cancer cells induce a massive influx of immunosuppressive M2-like macrophages, upregulate immune checkpoints, and impair effector T cell functions during peritoneal dissemination; these collectively create a highly angiogenic and immunosuppressive milieu that is resistant to anti-PD-1 monotherapy. Intraperitoneal administration of a STING agonist suppressed aberrant angiogenesis, increased pericyte coverage, and normalized tumor vessels, thereby facilitating the infiltration of activated CD8+ T cells into peritoneal tumor nodules. Moreover, STING activation reprogramed tumor-associated macrophages toward the M1 phenotype. STING activation converted immunologically cold peritoneal tumors into T-cell-inflamed tumors in a type-I interferon-dependent manner. Lastly, the STING agonist synergistically cooperated with PD-1 and/or COX2 blockade to further suppress the peritoneal dissemination of colon cancer, resulting in complete eradication of tumor and ascites, and inducing durable antitumor immunity.Conclusions STING activation can normalize the peritoneal vascular and immune microenvironment, providing a rationale for a novel combination therapeutic strategy for peritoneal carcinomatosis in colon cancer.

Abstract Background Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). Methods In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay. Results Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964. Conclusions Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.

Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). Although indoleamine 2,3-dioxygenase (IDO)-selective inhibitors have been developed to suppress the Kyn pathway, the results were not satisfactory due to the presence of various opposing mechanisms. Here, we employed an orally administered novel Kyn pathway regulator to overcome the limitation of anti-tumor immune response. We identified a novel core structure that inhibited both IDO and TDO. An orally available lead compound, STB-C017 (designated hereafter as STB), effectively inhibited the enzymatic and cellular activity of IDO and TDO in vitro. Moreover, it potently suppressed Kyn levels in both the plasma and tumor in vivo. STB monotherapy increased the infiltration of CD8+ T cells into TME. In addition, STB reprogrammed the TME with widespread changes in immune-mediated gene signatures. Notably, STB-based combination immunotherapy elicited the most potent anti-tumor efficacy through concurrent treatment with immune checkpoint inhibitors, leading to complete tumor regression and long-term overall survival. Our study demonstrated that a novel Kyn pathway regulator derived using deep learning technology can activate T cell immunity and potentiate immune checkpoint blockade by overcoming an immunosuppressive TME.

Background Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC.Methods PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay.Results JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone.Conclusions Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.

Summary: Stress-driven ribosome dysfunction triggers an eIF2α-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2α kinases, protein kinase R (PKR) expression positively associates with poor prognoses for colorectal cancer (CRC) patients. We identified PKR-linked Wnt signaling networks that facilitate early inflammatory niche and epithelial-mesenchymal transitions of tumor tissues in response to ribosomal insults. However, the downstream Wnt signaling target fibrogenic connective tissue growth factor (CTGF/CCN2) regulates the nuclear translocation of β-catenin in a negative feedback manner. Moreover, dwindling expression of the Wnt/β-catenin pathway-regulator CTGF triggers noncanonical Wnt pathway-mediated exacerbation of intestinal cancer progression such as an increase in cancer stemness and acquisition of chemoresistance in the presence of ribosomal insults. The Wnt-CTGF-circuit-associated landscape of oncogenic signaling events was verified with clinical genomic profiling. This ribosome-associated wave of crosstalk between stress and oncogenes provides valuable insight into potential molecular interventions against intestinal malignancies.

G3BP1 is RasGAP SH3 domain binding protein 1 that interacts with 48S pre-initiation complex when translation is stalled. Here, Twiss and colleagues show that neuronal G3BP1 can negatively regulate axonal mRNA translation, and inhibit axonal regeneration after injury.

Abstract Background Exposure to low levels of volatile organic compounds (VOCs) in ordinary life is suspected to be related to oxidative stress and decreased lung function. This study evaluated whether exposure to ambient VOCs in indoor air affects airway inflammation. Methods Thirty-four subjects from the hospital that had moved to a new building were enrolled. Symptoms of sick building syndrome, pulmonary function tests, and fractional exhaled nitric oxide (FeNO) were evaluated, and random urine samples were collected 1 week before and after the move. Urine samples were analyzed for VOC metabolites, oxidative stress biomarkers, and urinary leukotriene E4 (uLTE4) levels. Results The level of indoor VOCs in the new building was higher than that in the old building. Symptoms of eye dryness and eye irritation, as well as the level of a xylene metabolite (o-methylhippuric acid) increased after moving into the new building (p = 0.012, p = 0.008, and p

Background There are few studies on intensive care unit (ICU) patients in the Republic of Korea. We analyzed the characteristics and mortality changes of all ICU patients over the last 8 years. Methods This study used the cohort of the National Health Insurance Corporation, which provides medical care to all residents of the Republic of Korea. The cohort consists of patients aged 20 years or older between 2003 and 2010 with a history of ICU admission. We analyzed changes in sex, age, household income, number of hospital beds, emergency admissions, and reasons for admission using the Cochran–Armitage trend test. The adjusted hazard ratios (HRs) of mortality according to these variables and year of admission were calculated by Cox proportional hazards regression. Results The proportion of patients aged ≥70 years increased over that period, as did their average age (by 3.6 years). During the 8-year study period, the 3-year mortality rate was 32.91%–35.83%. The overall mortality was higher in males and older patients, in those with a lower household income and higher Charlson Comorbidity Index (CCI) score, those admitted to a hospital with a smaller number of beds, and those admitted via the emergency room. There was no significant change in crude mortality rate over the 8-year study period; however, the adjusted HR showed a decreasing trend. Conclusions Patients admitted to the ICU were older and had higher CCI score. Nevertheless, there was a temporal trend toward a decrease in the HR of long-term mortality.

Various types of ginsenosides are present in ginseng and have been recognized for their health-promoting effects. Compound K (CK) is a metabolite of ginsenoside Rb1 and reportedly exerts chemotherapeutic effects against several types of cancers. However, the anti-cancer effect and the molecular mechanism of CK against hormone-independent breast cancer is unknown. Through a direct comparison, it was discovered that CK elicits the strongest anti-cancer effect against breast cancer cells when compared to other ginsenosides. CK treatment suppresses the growth of hormone-independent human breast cancer cells and induces G1 phase cell cycle arrest. CK also markedly suppresses tumor growth in a mouse xenograft model, concomitant with the suppression of cyclin D1 via protein degradation. These findings suggest that CK can be used to target hormone-independent breast cancers by inducing degradation of cyclin D1.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up. Methods We analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups. Results PCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization. Conclusions Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.

Research in new alloy compositions and treatments may allow the increased strength of mass-produced, intricately shaped parts. Here authors introduce a superplastic medium manganese steel which has an inexpensive lean chemical composition and which is suited for conventional manufacturing processes.

Purpose We aimed to investigate the triage results and the degree of agreement between prehospital and hospital stages of pediatric patients who visited the emergency department (ED) via emergency medical service providers (EMSP) in comparison with adult patients. Methods We retrospectively reviewed 8,152 pediatric patients who visited a regional emergency medical center ED via EMSP from January 2015 to December 2015. Pediatric patients were defined as younger than 15 years according to the Korean Triage and Acuity Scale (KTAS). Given the difference of the triage tools of the prehospital (EMSP) and hospital (KTAS) stages, we performed the re-triage into “critical” and “non-critical”. Comparisons of characteristics between pediatric and adult patients were made using chi-square tests. The degree of agreement between the tools was analyzed using κanalysis. Results Of 8,152 patients, 654 (8.0%) were pediatric patients. Direct medical control was more frequently performed to adult patients (P < 0.001). Critical patients were more common among adults (12.2% by KTAS, 24.8% by EMSP) than children (3.5% by KTAS, 14.1% by EMSP). The κ value of pediatric patients was lower than that of adult patients (0.09 [poor]; 95% confidence interval [CI], 0.01-0.18 vs. 0.38 [fair]; 95% CI, 0.35-0.40). Conclusion Pediatric patients transferred by EMSP showed lower severity and degree of agreements of the triage results between prehospital and hospital stages than adult patients. It is necessary to pay particular attention to pediatric triage in a pre-hospital setting.

Abstract Recently, Fe-Mn twinning-induced plasticity steels with an austenite phase have been the course of great interest due to their excellent combination of tensile strength and ductility, which carbon steels have never been able to attain. Nevertheless, twinning-induced plasticity steels also exhibit a trade-off between strength and ductility, a longstanding dilemma for physical metallurgists, when fabricated based on the two alloy design parameters of stacking fault energy and grain size. Therefore, we investigated the tensile properties of three Fe-Mn austenitic steels with similar stacking fault energy and grain size, but different carbon concentrations. Surprisingly, when carbon concentration increased, both strength and ductility significantly improved. This indicates that the addition of carbon resulted in a proportionality between strength and ductility, instead of a trade-off between those characteristics. This new design parameter, C concentration, should be considered as a design parameter to endow Fe-Mn twinning-induced plasticity steel with a better combination of strength and ductility.

Objective We investigated the association between lactate clearance or serum lactate levels and neurologic outcomes or in-hospital mortality in cardiac arrest survivors who were treated with targeted temperature management (TTM). Methods A retrospective analysis of data from cardiac arrest survivors treated with TTM between 2012 and 2015 was conducted. Serum lactate levels were measured on admission and at 12, 24, and 48 hours following admission. Lactate clearance at 12, 24, and 48 hours was also calculated. The primary outcome was neurologic outcome at discharge. The secondary outcome was in-hospital mortality. Results The study included 282 patients; 184 (65.2%) were discharged with a poor neurologic outcome, and 62 (22.0%) died. Higher serum lactate levels at 12 hours (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.006 to 1.331), 24 hours (OR, 1.320; 95% CI, 1.084 to 1.607), and 48 hours (OR, 2.474; 95% CI, 1.459 to 4.195) after admission were associated with a poor neurologic outcome. Furthermore, a higher serum lactate level at 48 hours (OR, 1.459; 95% CI, 1.181 to 1.803) following admission was associated with in-hospital mortality. Lactate clearance was not associated with neurologic outcome or in-hospital mortality at any time point after adjusting for confounders. Conclusion Increased serum lactate levels after admission are associated with a poor neurologic outcome at discharge and in-hospital mortality in cardiac arrest survivors treated with TTM. Conversely, lactate clearance is not a robust surrogate marker of neurologic outcome or in-hospital mortality.

Microchips are widely used to separate circulating tumor cells (CTCs) from whole blood by virtues of sophisticated manipulation for microparticles. Here, we present a chip with an 8 μm high and 27.9 mm wide slit to capture cancer cells bound to 3 μm beads. Apart from a higher purity and recovery rate, the slit design allows for simplified fabrication, easy cell imaging, less clogging, lower chamber pressure and, therefore, higher throughput. The beads were conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) to selectively bind to breast cancer cells (MCF-7) used to spike the whole blood. The diameter of the cell-bead construct was in average 23.1 μm, making them separable from other cells in the blood. As a result, the cancer cells were separated from 5 mL of whole blood with a purity of 52.0% and a recovery rate of 91.1%, and also we confirmed that the device can be applicable to clinical samples of human breast cancer patients. The simple design with microslit, by eliminating any high-aspect ratio features, is expected to reduce possible defects on the chip and, therefore, more suitable for mass production without false separation outputs.

The effect of friction stir welding on microstructure and corrosion property was studied in Fe-30Mn-3Al-3Si (wt.%) twinning-induced plasticity steel using both an electron backscattered diffractometer and electrochemical testing (i.e., polarization test and electrochemical impedance spectroscope). The stir zone has a relatively higher corrosion resistance with uniform dissolution on the surface despite after welding, whereas the base metal shows localized corrosion attack with deep and long degradation along the grain boundaries. This is due to the corrosion-resistant coincidence site lattice boundaries caused by discontinuous dynamic recrystallization via the grain boundary bulging during the friction stir welding.

Traditionally, studies on the power generation performance analysis of the photovoltaic (PV) modules used in building-integrated PV (BIPV) systems have been based on computer simulations and actual experiments with constraints, resulting in the results being inaccurate and limited. This paper proposes a two-step analysis method that results in a more versatile and reliable means of analysis. The steps are: (1) construction of a mock-up test building in the form of BIPV systems and the collection of a massive amount of operational data for one year; and (2) a statistical analysis of the acquired data using Minitab software (Version: 17, Manufacturer: Minitab Inc., State College, PA, USA) to examine the power generation performance. The constructed BIPV mock-up applies design elements such as material types (c-Si and a-Si) and various directions and angles for different module installations. Prior to the analysis, the reliability of the large database (DB) constructed from the acquired data is statistically validated. Then, from the statistical correlation analysis of the DB, several plots that visualize the performance characteristics governed by design elements, including contour plots that show the region of higher performance, are generated. Further, a regression model equation for power generation performance is derived and verified. The results of this study will be useful in determining whether a BIPV system should be adopted in a building’s architectural design and, subsequently, selecting design element values for an actual BIPV system.