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The purpose of this study is to examine the normal accident-inducing effect of two network positions: status and structural holes, which are often regarded as critical sources of relational advantages. Contrary to the existing theoretical and practical view that accidents occur due to operational or engineering problems, we suggest that an organization’s status and structural holes in the interorganizational alliance network can also cause accidents. Drawing upon insights from normal accident theory, which highlights the accident-inducing effects of complexity, tight coupling, and slack shortage, we argue that differentiation costs stemming from status and complexity costs from structural holes increase the likelihood of accidents occurring. Moreover, slack shortage increases the accident-inducing effect of status by augmenting differentiation costs, whereas they reduce the accident-inducing effect of structural holes by diminishing complexity costs. The generalized estimating equations results of our empirical study of the U.S. airline industry from 1978 to 2011 strongly support our theoretical arguments. Accidents are more likely to occur when a focal airline holds a higher status in interfirm alliance networks and occupies a structural-hole rich position. Additionally, our results suggest that a shortage of human resource slack amplifies the accident-inducing effect of status while mitigating the effect of structural holes. The implications of the unintended negative outcomes of presumably advantageous network positions and the relational sources of accidents are discussed.

Abstract Purpose There is a lack of real‐world data in Asian populations for brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non‐small cell lung cancer (NSCLC). This study analysed real‐world outcomes and dosing patterns for brigatinib in patients with crizotinib‐refractory ALK+ NSCLC in South Korea. Methods This retrospective, non‐interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. Results The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3–48) months. Median follow‐up after brigatinib initiation was 18 (range 0–34) months. Overall, 88.5% of patients received full‐dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2–not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2‐year OS rate was 68.7%. Conclusions In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real‐world clinical benefit as second‐line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea.

Abstract Background Recently, the fine dust problem caused by rapid industrialization and science and technological development has emerged as a severe social issue worldwide. This also increases the interest in its effect on human life. In particular, there is a growing concern about the harm of fine dust in Korea. Methods This study is based on the PM 2.5 data from 2017 to 2021 provided by Air Korea to estimate changes in ultrafine dust. In addition, the data from the Community Health Survey provided by the Korea Centers for Disease Control and Prevention (KCDC) from 2017 to 2021 were used to examine the effect between the change in ultra-fine dust and the prevalence of depression. A total of 229 local governments were included in the analysis. The Latent Growth Modeling was carried out to estimate the change in ultra-fine dust and the prevalence of depressions and verify the relationship between ultra-fine dust and the prevalence of depression. Results The analysis result revealed that the ultra-fine dust concentration continued to decrease from 2017 to 2021. However, the depression prevalence increased from an average of 2.60% in 2017 to an average of 3.12% in 2021, suggesting the need for adequate and sufficient welfare policies for depression treatment. As a result of estimating the initial value and change rate of ultra-fine dust and depression prevalence, the higher the initial value of ultra-fine dust, the greater the decrease in ultra-fine dust. In terms of depression, the lower the initial value of the prevalence of depression, the larger the increase in depression prevalence. Conclusions This study is significant in that it revealed the strong association of the longitudinal relationship between ultra-fine dust and depression, one of the biggest issues in Korea, by utilizing large-scale longitudinal data.

Autoimmune hemolytic anemia (AIHA) is a common complication after hematopoietic stem cell transplantation (HSCT). Although post-HSCT AIHA is associated with poor prognosis and is more resistant to treatment than primary AIHA, the standard treatment has not yet been determined. We report a case of post-HSCT AIHA, which occurred 9 years after unrelated donor bone marrow transplantation for acute biphenotypic leukemia. Steroid treatment was initially effective but prolonged steroid usage, due to recurrent relapses, caused avascular necrosis. Although rituximab was unsuccessful in preventing relapses, sirolimus was effective in allowing the discontinuation of steroid treatment and sustaining transfusion-free status. Sirolimus, previously reported to be effective in pediatric post-HSCT AIHA and AIHA after solid organ transplantation, may be effective in adult post-HSCT AIHA as well.

BackgroundManaging complex vascular anomalies in pediatric care requires comprehensive approaches. Sirolimus, an mTOR inhibitor with immunosuppressive and anti-angiogenic properties, offers promise. We evaluated sirolimus's effectiveness and safety in pediatric patients with complex vascular anomalies at a tertiary children's hospital.MethodsOur study included 20 patients, aged 1 month to 19 years, with diverse vascular anomalies resistant to conventional therapies or located in high-risk areas precluding surgery. The evaluation of response encompassed measuring the reduction in the size of the targeted vascular or lymphatic lesions as observed on radiologic imaging, along with considering improvements reported by the patients.ResultsPatients used sirolimus for a median of 2.1 years, ranging from 0.6–4.3 years. Results indicated that 60% of patients achieved complete or partial response (CR/PR), whereas 40% had stable disease (SD). Notably, no disease progression occurred. Lesion size assessment was complex, yet patients' self-reported improvements were considered. Three patients reinitiated sirolimus after discontinuation due to worsening lesions. Sirolimus treatment demonstrated good tolerability, with minor complications except for one case of Pneumocystis jiroveci pneumonia. Group comparisons based on response highlighted better outcomes in patients with vascular tumors (CR/PR group 58.0% vs. SD group 0.0%, P = 0.015) or localized measurable lesions (83.3% vs. 12.5%, P = 0.005).ConclusionOur study underscores sirolimus's potential for treating complex vascular anomalies in pediatric patients. Challenges associated with optimal treatment duration and concurrent interventions necessitate a comprehensive approach and genetic testing to optimize outcomes.

Ice algae thriving within sea ice play a crucial role in transferring energy to higher trophic levels and influencing biogeochemical processes in polar oceans; however, the distribution of organic matter within the ice interior is not well understood. This study aimed to investigate the vertical distribution of organic matter, including chlorophyll a (Chl-a), particulate organic carbon and nitrogen (POC and PON), carbohydrates (CHO), proteins (PRT), lipids (LIP), and food material (FM), within the sea ice. Samples were collected from the bottom, middle, and top sections of the sea ice column near Cambridge Bay during the spring of 2018. Based on the δ13C signature, biochemical composition, and POC contribution of biopolymeric carbon (BPC), the organic substances within the sea ice were predominantly attributed to marine autotrophs. While the highest concentrations of each parameter were observed at the sea ice bottom, notable concentrations were also found in the upper sections. The average sea ice column-integrated Chl-a concentration was 5.05 ± 2.26 mg m−2, with the bottom ice section contributing 59% (S.D. = ± 10%) to the total integration. The column-integrated concentrations of FM, BPC, POC, and PON were 2.05 ± 0.39, 1.10 ± 0.20, 1.47 ± 0.25, and 0.09 ± 0.03 g m−2, respectively. Contributions of the bottom ice section to these column-integrated concentrations varied for each parameter, with values of 20 ± 6, 21 ± 7, 19 ± 5, and 28 ± 7%, respectively. While the bottom ice section exhibited a substantial Chl-a contribution in line with previous studies, significantly higher contributions of the other parameters were observed in the upper sea ice sections. This suggests that the particulate matter within the interior of the sea ice could potentially serve as an additional food source for higher trophic grazers or act as a seeding material for a phytoplankton bloom during the ice melting season. Our findings highlight the importance of comprehensive field measurements encompassing the entire sea ice section to better understand the distribution of organic carbon pools within the sea ice in the Arctic Ocean.

Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase β and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.

Background: The optimal conditioning regimen of tandem high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for high-risk neuroblastoma (HR-NBL) has not been established. The efficacy of 131I-MIBG therapy is under exploration in newly diagnosed HR-NBL patients. Here, we compared the outcomes of tandem HDC/ASCT between the 131I-MIBG combination and non-MIBG groups. Methods: We retrospectively analyzed the clinical data of 33 HR-NBL patients who underwent tandem HDC/ASCT between 2007 and 2021 at the Seoul National University Children’s Hospital. Results: The median age at diagnosis was 3.6 years. 131I-MIBG was administered to 13 (39.4%) of the patients. Thirty patients (90.9%) received maintenance therapy after tandem HDC/ASCT, twenty-two were treated with isotretinoin ± interleukin-2, and eight received salvage chemotherapy. The five-year overall survival (OS) and event-free survival (EFS) rates of all patients were 80.4% and 69.4%, respectively. Comparing the 131I-MIBG combined group and other groups, the five-year OS rates were 82.1% and 79.7% (p = 0.655), and the five-year EFS rates were 69.2% and 69.6% (p = 0.922), respectively. Among the adverse effects of grade 3 or 4, the incidence of liver enzyme elevation was significantly higher in the non-131I-MIBG group. Conclusions: Although tandem HDC/ASCT showed promising outcomes, the 131I-MIBG combination did not improve survival rates.

A lumen-apposing metal stent (LAMS) is a saddle-shaped stent with large flanges at both ends, thereby preventing stent migration and helping with approximation of the adjacent structures. We report the case of a 25-year-old female with remnant choledochal cyst which was successfully treated with LAMS after initial treatment failure with a plastic stent. Although complete excision of the cyst is the definite treatment of choledochal cysts, endoscopic ultrasonography-guided cystoduodenostomy can be considered in cases wherein surgery is not feasible and dysplasia is not present. LAMS may be preferred to plastic stents for effective resolution of remnant choledochal cyst and prevention of ascending infection.

BackgroundA low-degree tumor necrosis after neoadjuvant chemotherapy is a poor prognostic factor for osteosarcoma (OSA). However, the role of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation in OSA remains controversial. We analyzed the treatment outcomes and prognostic factors of nonmetastatic OSA and compared the HDC and conventional chemotherapy (CC) outcomes of patients with 90% (good response [GR]), whereas most cases with

(1) Background: Hospitalists are healthcare providers who focus on hospitalized patients, but research on the roles of pediatric hospitalists is lacking. This study investigates the role of a supervisor-type hospitalist in a pediatric hematology/oncology ward at a tertiary children’s hospital, assessing the impact on satisfaction levels among patient caregivers, resident physicians, and nurses. (2) Methods: A retrospective analysis and online surveys were conducted to assess satisfaction levels before and after the introduction of hospitalists in the Department of Pediatric Hematology/Oncology at Seoul National University Children’s Hospital in the Republic of Korea. (3) Results: The introduction of hospitalists led to a 19.3% reduction in prescription error interventions over six months. Unexpected transfers to the intensive care unit decreased from 1.4% to 0.7% (p = 0.229). Patient caregivers reported elevated satisfaction levels with physicians (rated 8.47/10), and there was a significant enhancement in overall satisfaction among nurses (increasing from 3.23 to 4.23/5, p < 0.001). The majority of resident physicians (83.3%) expressed contentment with the hospitalist system, with 77% indicating an interest in transitioning to a hospitalist role. However, these resident physicians also expressed concerns regarding job stability. (4) Conclusions: Supervisor-type pediatric hospitalists have the potential to elevate satisfaction levels not only among patient caregivers but also among nurses and resident physicians, showing promise in improving medical care quality. Nonetheless, ensuring favorable perception and securing job stability within the hospitalist system are pivotal for achieving successful implementation.

Quantifying the temporal variability in phytoplankton productivity is essential for improving our understanding of carbon (C) and nitrogen (N) dynamics and energy flows in natural aquatic ecosystems. Samples were collected at three-day intervals from December 2018 to January 2019 from fixed station in Marian Cove, Antarctica to determine the C and N (NO3- and NH4+) uptake by phytoplankton. Considerable fluctuations in the total C and N productivities were observed, which led to dynamic changes in the phytoplankton communities and a stronger coupling between the phytoplankton biomass. The increased rate of NO3- uptake coincided with an enhanced C uptake mainly by microphytoplankton (>20 µm), followed by an increase in NH4+ uptake towards the end of sampling period. However, the 6 m s-1), which rapidly decreased the total chl-a, C and N uptake rate to ~4% of the highest values (0.6 mg m-3, 1.0 mg C m-3 h-1, 0.1 mg N m-3 h-1, respectively) on January 12. The phytoplankton community was also replaced by neritic and ice-related species. These findings suggest that strong temporal shifts in phytoplankton C and N assimilation are strongly influenced by external forces (wind stress).

The spatio-temporal distributions of the epipelagic mesozooplankton community in the western Ross Sea region marine protected area (RSR MPA) were investigated. Mesozooplankton surveys were conducted in February 2018, January 2019, and March 2020 from an approximate depth of 200 m to address the essential environmental factors influencing the mesozooplankton community structure. Our results showed that the mesozooplankton community of the western RSR MPA could be affected by the various ecological factors, depending on their temporal and spatial variations. The community structure in 2018 was distinguished by its chlorophyll-a (Chl-a) concentration during the summer bloom phase in the late summer. Taxa observed in 2019 were divided into four significantly different groups according to the body size of the community composition. This differentiation could be derived from predation pressure, inducing a trophic cascade. Taxa in the 2020 samples were separated into five different groups based on temperature; during the 2020 survey, the water temperature was low and sea ice covered the whole continental shelf in the Ross Sea. Additionally, comparing the results from the three interannual surveys, although the communities clustered according to the survey period, the continental shelf groups were quite dissimilar despite overlapping geographically. Taken all together, the mesozooplankton community of the western RSR MPA changed according to changes in several ecological factors, such as temperature, Chl-a concentration, and predation pressure. The occurrence of summer blooms and the decline in water temperature mainly regulated the mesozooplankton community structure in the late summer.

Abstract Background Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy. Methods We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children’s Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients’ choice. Results The median age at diagnosis was 11.9 (range, 3.8–25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p

Our understanding of ice algal responses to the recent changes in Arctic sea ice is impeded by limited field observations. In the present study, environmental characteristics of the landfast sea-ice zone as well as primary production and macromolecular composition of ice algae and phytoplankton were studied in the Kitikmeot Sea near Cambridge Bay in spring 2017. Averaged total chlorophyll-a (Chl-a) concentration was within the lower range reported previously for the same region, while daily carbon uptake rates of bottom-ice algae were significantly lower in this study than previously reported for the Arctic. Based on various indicators, the region's low nutrient concentrations appear to limit carbon uptake rates and associated accumulation of bottom-ice algal biomass. Furthermore, the lipids-dominant biochemical composition of bottom-ice algae suggests strong nutrient limitation relative to the distinctly different carbohydrates-dominant composition of phytoplankton. Together, the results confirm strong nitrate limitation of the local marine system.

Background: The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway. Methods: The inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis. Results: Treatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation. Conclusion: Our results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases. Keywords: Adipogenesis, BST204, H2BS36 phosphorylation, S6K1, Wnt genes

Nucleocytoplasmic large DNA viruses (NCLDVs) infect various marine eukaryotes. However, little is known about NCLDV diversity and their relationships with eukaryotic hosts in marine environments, the elucidation of which will advance the current understanding of marine ecosystems. This study characterizes the interplay between NCLDVs and the eukaryotic plankton community (EPC) in the sub-Arctic area using metagenomics and metabarcoding to investigate NCLDVs and EPC, respectively, in the Kongsfjorden ecosystem of Svalbard (Norway) in April and June 2018. Gyrodinium helveticum (Dinophyceae) is the most prevalent eukaryotic taxon in the EPC in April, during which time Mimiviridae (31.8%), Poxviridae (25.1%), Phycodnaviridae (14.7%) and Pandoraviridae (13.1%) predominate. However, in June, the predominant taxon is Aureococcus anophagefferens (Pelagophyceae), and the NCLDVs, Poxviridae (32.9%), Mimiviridae (29.1%), and Phycodnaviridae (18.5%) appear in higher proportions with an increase in Pelagophyceae, Bacillariophyceae, and Chlorophyta groups. Thus, differences in NCLDVs may be caused by changes in EPC composition in response to environmental changes, such as increases in water temperature and light intensity. Taken together, these findings are particularly relevant considering the anticipated impact of NCLDV-induced EPC control mechanisms on polar regions and, therefore, improve the understanding of the Sub-Arctic Kongsfjorden ecosystem.

Primary enucleation is a life-saving treatment for advanced intraocular retinoblastoma, particularly in patients with poor visual potential and functional contralateral eyes. This single-center study presents the treatment outcomes of patients with unilateral retinoblastoma who received primary enucleation and adjuvant chemotherapy with cyclophosphamide, vincristine, doxorubicin, and intrathecal methotrexate (CVDM) between 2000 and 2020. Twenty patients were enrolled in the study. The median age at diagnosis was 26 months (range, 1–45). Eighteen patients (90%) were in group E and two (10%) were in group D, according to the intraocular classification of retinoblastoma guidelines. Excluding one patient with an inadequate specimen, 19 patients (95%) had optic nerve involvement (ONI) at least up to the lamina cribrosa. Eight patients (40%) had choroidal invasion in addition to ONI. Two patients (10%) were surgical resection margin positive. The overall and event-free survival rates were 100% and 95%, respectively, for a median follow-up duration of 102.24 months (range 24.2–202.9). There were no relapses or deaths due to any cause, but one patient developed secondary rhabdomyosarcoma 99.6 months after chemotherapy. Treatment was well tolerated, with minimal hematotoxicity and hepatotoxicity. CVDM as a post-enucleation chemotherapy for advanced intraocular retinoblastoma has excellent outcomes with tolerable toxicity. However, in line with updated treatment trends, further risk stratification and lowering the treatment intensity should be considered. Continued long-term follow-up is required to further determine late effects.

Rapidly changing conditions in high-latitude coastal systems can significantly impact biogeochemical cycles because these systems are strongly influenced by freshwater discharged from melting glaciers and streams on land. Generally, Antarctic coastal areas are considered high-productivity areas in which phytoplankton growth prevails under various environmental conditions (e.g., oceanographic and meteorological conditions). This study provides carbon uptake rates of phytoplankton in Marian Cove during summer (January-February 2019). Daily depth-integrated carbon uptake varied greatly and averaged 0.8 g C m–2 day–1, with a maximum of 4.52 mg g C m–2 day–1 recorded on 14 January. Similarly, the observed biomass standing stocks were very high (up to 19.5 mg m–3 chlorophyll a) and were dominated by microphytoplankton (20–200 μm), representing 84% of total chlorophyll a (chl-a). The depth-integrated chl-a and carbon uptake decreased from outer to inner areas (close to the glacial front) in the cove. As the austral summer progressed, the freshening of the surface waters coincided with high water stability and suspended material and with low productivity when nanophytoplankton were present (2–20 μm; >60%). These findings suggest that both photosynthetically active radiation penetrating the water column and enhanced turbidity control light availability for phytoplankton, as well as their community compositions.

This paper examines the mechanisms through which higher education institutions (HEIs) explore, focusing on organizational status and institutional logic. We hypothesize that the exploration mechanisms differ depending on the public and private sectors. Revisiting middle-status conformity, we assert that the U-shaped relationship is stronger for private HEIs than public HEIs, as private HEIs are more concerned about status. We also argue that the congruence of institutional logics between HEIs and their funding partners foster exploration based on the sense of security. In contrast, when HEIs receive funding from partners with incongruent logics, they explore less because of their tendency to avoid additional uncertainty. We empirically test our hypotheses using data on US HEIs between 2014 and 2020. Our results demonstrate that a U-shaped relationship between status and exploration is stronger for private HEIs. Moreover, non-market funding providers, whose institutional logic congruent with public HEIs yet incongruent with private HEIs, increase the exploration of public HEIs and decrease the exploration of private HEIs. By integrating theories on organizational learning, status, and institutional theory, our study contributes to a nuanced understanding of the differences between public and private HEIs with respect to exploration.

Marine particulate organic matter (POM) largely derived from phytoplankton is a primary food source for upper trophic consumers. Their biochemical compositions are important for heterotrophs. Especially, essential amino acids (EAAs) in phytoplankton are well known to have impacts on the survival and egg productions of herbivorous zooplankton. To estimate the nutritional quality of POM, the biochemical compositions [biomolecular and amino acid (AA) compositions] of POM were investigated in the northwestern Ross Sea during the late austral summer in 2018. Carbohydrates (CHO) accounted for the highest portion among different biomolecules [CHO, proteins (PRT), and lipids (LIP)] of POM. However, the higher contribution of PRT and lower contribution of CHO were observed in the southern section of our study area compared to those in the northern section. The spatial distribution of total hydrolyzable AAs in POM was considerably influenced by phytoplankton biomass, which indicates that the main source of particulate AA was generated by phytoplankton. Our results showed that the relative contribution of EAA to the total AAs was strongly associated with EAA index (EAAI) for determining protein quality. This result indicates that higher EAA contribution in POM suggests a better protein quality in consistency with high EAAI values. In this study, variations in the biochemical compositions in POM were principally determined by two different bloom-forming taxa (diatoms and Phaeocystis antarctica). The southern region dominated majorly by diatoms was positively correlated with PRT, EAA, and EAAI indicating a good protein quality, while P. antarctica-abundant northern region with higher CHO contribution was negatively correlated with good protein quality factors. Climate-driven environmental changes could alter not only the phytoplankton community but also the physiological conditions of phytoplankton. Our findings could provide a better understanding for future climate-induced changes in the biochemical compositions of phytoplankton and consequently their potential impacts on higher trophic levels.

Classification of clinical symptoms and diagnostic microbiology are essential to effectively employ antimicrobial therapy for lower respiratory tract infections (LRTIs) in a timely manner. Empirical antibiotic treatment without microbial identification hinders the selective use of narrow-spectrum antibiotics and effective patient treatment. Thus, the development of rapid and accurate diagnostic procedures that can be readily adopted by the clinic is necessary to minimize non-essential or excessive use of antibiotics and accelerate patient recovery from LRTI-induced damage. We developed and validated a multiplex real-time polymerase chain reaction (mRT-PCR) assay with good analytical performance and high specificity to simultaneously detect four bacterial pathogens causing pneumonia: Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Moraxella catarrhalis. The analytical performance of mRT-PCR against target pathogens was evaluated by the limit of detection (LOD), specificity, and repeatability. Two hundred and ten clinical specimens from pneumonia patients were processed using an automatic nucleic acid extraction system for the "respiratory bacteria four" (RB4) mRT-PCR assay, and the results were directly compared to references from bacterial culture and/or Sanger sequencing. The RB4 mRT-PCR assay detected all target pathogens from sputum specimens with a coefficient of variation ranging from 0.29 to 1.71 and conservative LOD of DNA corresponding to 5 × 102 copies/reaction. The concordance of the assay with reference-positive specimens was 100%, and additional bacterial infections were detected from reference-negative specimens. Overall, the RB4 mRT-PCR assay showed a more rapid turnaround time and higher performance that those of reference assays. The RB4 mRT-PCR assay is a high-throughput and reliable tool that assists decision-making assessment and outperforms other standard methods. This tool supports patient management by considerably reducing the inappropriate use of antibiotics.

Many oceans are currently undergoing rapid changes in environmental conditions such as warming temperature, acidic water condition, coastal hypoxia, etc [...]

We investigated pigment and mycosporine-like amino acid (MAA) concentrations of phytoplankton and Northern krill (Thysanoessa sp.) in sub-Arctic Kongsfjorden. Chlorophyll a (Chl-a) concentrations in the surface and middle-layer water were 0.44 μg L−1 (±0.17 μg L−1) and 0.63 μg L−1 (±0.25 μg L−1), respectively. Alloxanthin (Allo, a marker of cryptophytes) was observed at all stations, and its mean values for surface and middle-layer water were 0.09 μg L−1 (±0.05 μg L−1) and 0.05 (±0.02 μg L−1), respectively. The mean MAA-to-Chl-a ratios at the surface (3.31 ± 2.58 μg (μg Chl-a)−1) were significantly higher than those in the middle-layer water (0.88 ± 0.49 μg (μg Chl-a)−1), suggesting that these compounds play an important role in reducing UV photodamage. In gut pigment levels of Northern krill, the most abundant accessory pigment was Allo (2.79 ± 0.33 μg g−1 dry weight; d.w.), as was the accumulation of Chl-a (8.29 ± 1.13 μg g−1 d.w.). The average concentration of MAAs was 1.87 mg g−1 d.w. (±0.88 mg g−1 d.w.) in krill eyes, which was higher than that in all other body parts (0.99 ± 0.41 mg g−1 d.w.), except for the gut. Thysanoessa sp. was found to contain five identified MAAs (shinorine, palythine, porphyra-334, mycosporine-glycine, and M-332) in the krill eye, whereas shinorine and porphyra-334 were only observed in the krill body, not the eyes and gut. These findings suggest that Northern krill accumulate MAAs of various compositions through the diet (mainly cryptophytes) and translocate them among their body parts as an adaptation for photoprotection and physiological demands.

Abstract Background With the growing amount of clinical research, regulations and research ethics are becoming more stringent. This trend introduces a need for quality assurance measures for ensuring adherence to research ethics and human research protection beyond Institutional Review Board approval. Audits, one of the most effective tools for assessing quality assurance, are measures used to evaluate Good Clinical Practice (GCP) and protocol compliance in clinical research. However, they are laborious, time consuming, and require expertise. Therefore, we developed a simple auditing process (a screening audit) and evaluated its feasibility and effectiveness. Methods The screening audit was developed using a routine audit checklist based on the Severance Hospital’s Human Research Protection Program policies and procedures. The measure includes 20 questions, and results are summarized in five categories of audit findings. We analyzed 462 studies that were reviewed by the Severance Hospital Human Research Protection Center between 2013 and 2017. We retrospectively analyzed research characteristics, reply rate, audit findings, associated factors and post-screening audit compliance, etc. Results Investigator reply rates gradually increased, except for the first year (73% → 26% → 53% → 49% → 55%). The studies were graded as “critical,” “major,” “minor,” and “not a finding” (11.9, 39.0, 42.9, and 6.3%, respectively), based on findings and number of deficiencies. The auditors’ decisions showed fair agreement with weighted kappa values of 0.316, 0.339, and 0.373. Low-risk level studies, single center studies, and non-phase clinical research showed more prevalent frequencies of being “major” or “critical” (p = 0.002,

It is complicated to establish a consensus on the management and diagnosis of malignancy-triggered hemophagocytic lymphohistiocytosis (M-HLH) in children, as an initial presentation of malignancy is complicated. In this paper, we analyze the clinical characteristics and outcomes of eight pediatric patients in which M-HLH was the initial presentation of malignancy. All patients had hematologic malignancies: three subcutaneous panniculitis-like T-cell lymphomas, two acute lymphoblastic leukemias, two anaplastic large cell lymphomas, and a systemic EBV + T-cell lymphoma of childhood. The incidence rate of M-HLH among leukemia and malignant lymphoma patients in our institution was 1.9%. From the initial diagnosis of HLH, the median time taken to be diagnosed as a malignancy was about 1.3 months. The majority of patients received HLH-targeted immunosuppression and/or etoposide at first. The patients’ clinical response to treatment for HLH and malignancies were varied. Five out of the eight patients died, one of whom died due to HLH-related cerebral edema after the initiation of chemotherapy. The median overall survival was 1.6 years. In order to improve the survival rate, the early detection of M-HLH, rapid screening for malignancy, and complete control of M-HLH with HLH-directed therapy followed by a thorough response monitoring are required.

The role of macrophage migration inhibitory factor (MIF) and autophagy in gastric cancer is not clear. We determined H. pylori infection status of the subjects and investigated the expression of MIF and autophagy markers (Atg5, LC3A and LC3B) in human gastric tissue at baseline. Then H. pylori eradication was done for H. pylori positive patients and MIF and Atg5 levels were investigated on each follow-up for both H. pylori-eradicated and H. pylori negative patients. Baseline tissue mRNA expression of MIF, Atg5, LC3A and LC3B was measured by real-time PCR in 453 patients (control 165, gastric dysplasia 82, and gastric cancer 206). Three hundred three patients (66.9%) had H. pylori infection at the time of enrollment. Only within H. pylori-positive group, MIF level was significantly elevated in patients with cancer than in control or dysplasia groups (P

Rapid climate warming and the associated melting of glaciers in high-latitude open fjord systems can have a significant impact on biogeochemical cycles. In this study, the uptake rates of carbon and nitrogen (nitrate and ammonium) of total phytoplankton and picophytoplankton (−2 day−1, with a mean of 0.7 ± 0.3 g C m−2 day−1, and 0.13 to 0.17 g N m−2 day−1, with a mean of 0.16 ± 0.02 g N m−2 day−1. Microphytoplankton (20–200 μm) accounted for 68.1% of the total chlorophyll a (chl-a) concentration, while picophytoplankton (Phaeocystis sp., a higher proportion of nano- and picophytoplankton chl-a (mean ± SD = 71.3 ± 16.4%) was observed in the relatively cold and turbid surface water in the inner fjord. Phytoplankton production (carbon uptake) decreased towards the inner fjord, while nitrogen uptake increased. The contrast in carbon and nitrogen uptake is likely caused by the gradient in glacial meltwater which affects both the light regime and nutrient availability. Therefore, global warming-enhanced glacier melting might support lower primary production (carbon fixation) with higher degrees of regeneration processes in fjord systems.

Analysis of the biochemical composition (carbohydrates, CHO; proteins, PRT; lipids, LIP) of particulate organic matter (POM, mainly phytoplankton) is used to assess trophic states, and the quantity of food material is generally assessed to determine bioavailability; however, bioavailability is reduced or changed by enzymatic hydrolysis. Here, we investigated the current trophic state and bioavailability of phytoplankton in the Chukchi Sea (including the Chukchi Borderland) during the summer of 2017. Based on a cluster analysis, our 12 stations were divided into three groups: the southern, middle, and northern parts of the Chukchi Sea. A principal component analysis (PCA) revealed that relatively nutrient-rich and high-temperature waters in the southern part of the Chukchi Sea enhanced the microphytoplankton biomass, while picophytoplankton were linked to a high contribution of meltwater derived from sea ice melting in the northern part of the sea. The total PRT accounted for 41.8% (±7.5%) of the POM in the southern part of the sea, and this contribution was higher than those in the middle (26.5 ± 7.5%) and northern (26.5 ± 10.6%) parts, whereas the CHO accounted for more than half of the total POM in the northern parts. As determined by enzymatic hydrolysis, LIP were more rapidly mineralized in the southern part of the Chukchi Sea, whereas CHO were largely used as source of energy for higher trophic levels in the northern part of the Chukchi Sea. Specifically, the bioavailable fraction of POM in the northern part of the Chukchi Sea was higher than it was in the other parts. The findings indicate that increasing meltwater and a low nutrient supply lead to smaller cell sizes of phytoplankton and their taxa (flagellate and green algae) with more CHO and a negative effect on the total concentration of POM. However, in terms of bioavailability (food utilization), which determines the rate at which digested food is used by consumers, potentially available food could have positive effects on ecosystem functioning.

Mast cells play a pivotal role in IgE-mediated allergic responses. Development of specific inhibitors against FcεRI-associated proximal signaling molecules in mast cells may represent a promising therapeutic strategy for allergic diseases. We examined whether a novel synthetic compound, 3-butyl-1-chloro-8-(2-methoxycarbonyl)phenyl-5H-imidazo[1,5-b]isoquinolin-10-one (U63A05), could suppress antigen-stimulated degranulation and cytokine secretion in mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. U63A05 reversibly and dose-dependently inhibited degranulation of rat basophilic leukemia (RBL)-2H3 mast cells and bone marrow–derived mast cells (BMMCs) stimulated by antigen (IC50 values for RBL-2H3 and BMMCs were 4.1 and 4.8 μM, respectively). The secretion of inflammatory cytokines was also suppressed in antigen-stimulated mast cells. However, degranulation by thapsigargin, a typical calcium inducer, was not inhibited by U63A05. U63A05 exerts its inhibitory effect, to the same extent as in degranulation, on the activating phosphorylation of Syk and downstream signaling molecules, including LAT and SLP-76. Further downstream, the activating phosphorylations of Akt, Erk1/2, p38, and JNK were also inhibited. Finally, antigen-stimulated PCA was dose-dependently suppressed in mice (ED50, 26.3 mg/kg). Taken together, the results suggest that U63A05 suppresses the activation of mast cells and the mast cell–mediated allergic response through the inhibition of Syk activation in mast cells. Keywords:: 3-butyl-1-chloro-8-(2-methoxycarbonyl)phenyl-5H-imidazo[1,5-b]isoquinolin-10-one (U63A05), mast cell, IgE, type I hypersensitive response, syk

Purpose: This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. Materials and Methods: Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. Results: Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36–124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3–112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients’ endoscopy revealed a high incidence of atrophic gastritis in the antrum. Conclusions: The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS. [ABSTRACT FROM AUTHOR]