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Drawing on two multilingual qualitative datasets (Korean/English and German/English), this paper examines the dual role and positionalities of two researchers who simultaneously act as translators, as well as the implications of this dual role for multilingual qualitative research. This work is informed by transnational feminist translation studies and transnational feminist approaches to qualitative research, and founded on the two researchers' intimate familiarity with their participants' languages, contexts, and meaning-making processes. Considering the complexity of this familiarity, this work presents unique dilemmas—challenges and opportunities—with respect to translating, representing, and writing about multilingual qualitative data. [ABSTRACT FROM AUTHOR]

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai—a naturally growing species in South Korea—and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

We report a 4-year-old with Gorham–Stout disease (GSD) who was treated with a combination of bisphosphonate, sirolimus, and atenolol. A previously healthy 4-year-old girl presented with back pain after falling on her back 2 months prior. Thoracolumbar spine X-ray revealed diffuse compression spinal fractures in T9-L2. Magnetic resonance imaging (MRI) confirmed multiple compression fractures at T9-L5 and revealed a paraspinal mass along the T1-L1 level. Based on clinical, radiological, and histopathological findings, Gorham–Stout disease was diagnosed. Treatment with sirolimus (0.5 mg twice daily, 1.6 mg/m2) was initiated and intravenous bisphosphonate (pamidronate, 1 mg/kg for 3 days, total 3 mg/kg every 4 months) was added for back pain; she had immediate improvement in back pain. After 9 months with this treatment, she had a mild increase in paraspinal lymphangiomatosis and aggravation in T9-L5 compression fractures; atenolol was administered. The patient underwent 11 months of combination treatment with bisphosphonate, sirolimus, and atenolol, and MRI showed mild degree of reduction in the paraspinal lesions at L1-L5. The patient is currently in stable condition with no back pain or side effects. The triple combination treatment with bisphosphonate, sirolimus, and atenolol may be helpful in stabilizing the disease course of GSD. [ABSTRACT FROM AUTHOR]

Oxidative stress is an automatic mechanism responsible for the commencement and continuance of liver injury. In this study, an antioxidative peptide Val-Thr-Ala-Leu (VTAL) was purified from simulated gastrointestinal digestion of protein hydrolysates of the triploid oyster Magallana gigas. Significant antioxidant activity was identified, as well as a protective effect against acetaminophen (APAP)-induced human liver cancer (HepG2) cells. The results suggested that the antioxidant activity improved in a dose-dependent manner. The highest cell viability (88.105 ± 3.62%) was observed in 15 mM APAP-induced cells when treated with 25 μg/mL M. gigas peptide [M.g (pep)]. The peptide sequences include hydrophobic amino acids, which could be responsible for its chemoprotective and antioxidant activities. Treatment with M.g (pep) significantly promoted the proliferation of HepG2 cells, thus protecting them against APAP and imbuing them with significant antioxidant capacity. M.g (pep) could be beneficial for treating drug-induced oxidative stress and liver damage. Additionally, M.g (pep) could serve as an alternative to synthetic antioxidant drugs. [ABSTRACT FROM AUTHOR]

Existing research on the transit network design problem has tended to focus on minimizing the various costs for both transit operators and users. However, to implement an appropriate and effective transit network in urban environments, it is important not to overly simplify the intrinsically complex nature of real-life network designs. In particular, the minimization of variance in transit service levels typically employed in existing methods can be significantly improved by incorporating a transit equity component. This paper adopts a multiobjective approach that considers system efficiency, user inconvenience, and transit equity without the use of weights in order to design a more realistic and efficient transit network. In particular, the multiobjective Nondominated Sorting Genetic Algorithm-II and the neighborhood local search method are employed in a logit-based mode-choice model in order to incorporate the variable transit demand arising from the private vehicle traffic volume. A toy test network and a real-life network from the city of Goyang, Republic of Korea, are used to verify the effectiveness of the proposed model. The model finds a set of solutions that improve transit equity with minimal losses of other objectives when compared to existing approaches, which produce a significant variance in the level of service, mainly due to the spatially condensed and overlapping distribution of their transit networks. In addition, the relationship between the three objective functions and their resulting patterns in response to key influential factors are also analyzed to verify the robustness of the proposed method in response to changing future conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: The demand for fishmeal is increasing due to aquaculture development, but the supply is unstable. This indicates the need to reduce the fishmeal content in the feed and develop an optimal fish-feed formulation through substitutes. However, most studies on reducing fishmeal content in feed were conducted at the laboratory level. In this study, the application of a low-fishmeal diet as feed to olive flounder was evaluated in terms of growth-related factors, digestive physiology, and microbiota raised for five months in a fish farm using four feed formulations- FM70 [control (CON), 70% fishmeal], FM45 (45% fishmeal), FM35A (35% fishmeal), and FM35B (35% fishmeal + insect meal). There was no difference in growth-related factors, digestive physiology, and gut microbiota diversity compared with the CON-fed fish. Therefore, reducing the fishmeal content of the feed by up to 35% does not adversely affect growth and physiological characteristics under farm conditions. In olive flounder (Paralichthys olivaceus), growth performance, expression of growth-related factors, digestive physiology, and gut microbiota were assessed under farm conditions in the fish fed diets with low levels of fishmeal. Four experimental diets were prepared, FM70 [control (CON), 70% fishmeal], FM45 (45% fishmeal), FM35A (35% fishmeal), and FM35B (35% fishmeal + insect meal), and fed to the fish for five months. The CON-fed fish had the highest plasma GH, but IGF-1 and hepatic IGF-1 mRNA expression of the olive flounder fed diets with low-fishmeal levels did not significantly differ among diets. The intestinal villus length, muscular thickness, and the number of goblet cells were statistically similar, and ocular examination of hepatopancreas showed no discernable difference in all experimental diets. The chymotrypsin content of FM35B-fed fish is significantly lower, but trypsin and lipase contents are similar. The diversity of gut microbiota did not differ among groups, although the FM35B group had a higher composition of Firmicutes. Thus, a diet with reduced fishmeal content and several alternative protein sources can be used as feed ingredients in feed formulation for olive flounder reared under typical aquaculture farm conditions. [ABSTRACT FROM AUTHOR]

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species (ROS) and calcium ions (Ca2+) are representative signals of plant wound responses. Wounding triggers cell fate transition in detached plant tissues and induces de novo root organogenesis. While the hormonal regulation of root organogenesis has been widely studied, the role of early wound signals including ROS and Ca2+ remains largely unknown. Results: We identified that ROS and Ca2+ are required for de novo root organogenesis, but have different functions in Arabidopsis explants. The inhibition of the ROS and Ca2+ signals delayed root development in detached leaves. Examination of the auxin signaling pathways indicated that ROS and Ca2+ did not affect auxin biosynthesis and transport in explants. Additionally, the expression of key genes related to auxin signals during root organogenesis was not significantly affected by the inhibition of ROS and Ca2+ signals. The addition of auxin partially restored the suppression of root development by the ROS inhibitor; however, auxin supplementation did not affect root organogenesis in Ca2+-depleted explants. Conclusions: Our results indicate that, while both ROS and Ca2+ are key molecules, at least in part of the auxin signals acts downstream of ROS signaling, and Ca2+ acts downstream of auxin during de novo root organogenesis in leaf explants. [ABSTRACT FROM AUTHOR]

Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in regulating calcium influx, particularly in inflammation. Nootkatone, a natural sesquiterpenoid found in Alpinia oxyphylla and various citrus species, has gained attention for its diverse pharmacological properties, including anti-inflammatory effects. This study aimed to elucidate the potential of nootkatone in modulating ion channels associated with calcium signaling, particularly CRAC, KV1.3, and KCa3.1 channels, which play pivotal roles in immune cell activation and proliferation. Using electrophysiological techniques, we demonstrated the inhibitory effects of nootkatone on CRAC, KV1.3, and KCa3.1 channels in HEK293T cells overexpressing respective channel proteins. Nootkatone exhibited dose-dependent inhibition of channel currents, with IC50 values determined for each channel. Nootkatone treatment did not significantly affect cell viability, indicating its potential safety for therapeutic applications. Furthermore, we observed that nootkatone treatment attenuated calcium influx through activated CRAC channels and showed anti-proliferative effects, suggesting its role in regulating inflammatory T cell activation. These findings highlight the potential of nootkatone as a natural compound for modulating calcium signaling pathways by targeting related key ion channels and it holds promise as a novel therapeutic agent for inflammatory disorders. [ABSTRACT FROM AUTHOR]

Park, S.J. and Kim, J., 2023. How will the United Nations (UN) Biological Beyond National Jurisdiction (BBNJ) agreement affect the shipping industry in the future? In: Lee, J.L.; Lee, H.; Min, B.I.; Chang, J.-I.; Cho, G.T.; Yoon, J.-S., and Lee, J. (eds.), Multidisciplinary Approaches to Coastal and Marine Management. Journal of Coastal Research, Special Issue No. 116, pp. 398-402. Charlotte (North Carolina), ISSN 0749-0208. The discussion on the creation of a new international maritime order to change the freedom of the high seas, which has been maintained following the adoption of the United Nations Convention on the Law of the Sea (UNCLOS), is expected to be at a fever pitch. In 2004, the UN General Assembly (UNGA) adopted a resolution establishing an ad hoc working group on the conservation and sustainable use of marine biodiversity in the Areas Beyond National Jurisdiction (ABNJ). After 10 years of discussion till 2015, developed and developing countries agreed to create "a legally binding international instrument" and United Nations' member states finally agreed to a text on the Biological Beyond National Jurisdiction (BBNJ) agreement at the resumed 5th Intergovernmental Conference (IGC), which was held in March 2023. This international new order is anticipated to limit "freedom of the high seas" and significantly impact marine use, including navigation, fisheries, marine resources development, and marine scientific research. This study analyzes the effects of this new order on the shipping industry. To analyze this impact, changes in ship operating costs were calculated for container ships, dry cargo ships, and oil tankers under the assumption that two regulations apply to certain waters of Korean import routes: a reduction of average speeds by 1 knot and a 100-nautical-mile detour. Based on scenario analysis, when freight rates are high, shipping costs will rise in all scenarios regardless of fuel oil prices. However, profitability worsens when freight rates and fuel oil prices are low. Therefore, in responding to the adaptation of the UN BBNJ agreement, it is necessary to establish countermeasures for the shipping industry and strengthen cooperation systems with international organizations related to the UN BBNJ agreement. In addition, it is vital to improving the scenario and derive accurate results by cooperating with the industry. [ABSTRACT FROM AUTHOR]

Purpose: To compare surgical outcomes of sutureless flanged intraocular lens (IOL) fixation and conventional sutured scleral fixation (SF) for secondary IOL implantation in patients with IOL dislocation. Methods: This is a prospective, comparative cohort study on 103 consecutive patients (103 eyes) with IOL dislocation who underwent vitrectomy with IOL removal and sutured SF (53 eyes) or flanged IOL fixation (50 eyes). Operating time, best-corrected visual acuity (BCVA), refractive difference, IOL tilt and decentration using swept-source anterior segment OCT, and postoperative complications were measured for 12 months. Results: Operating time was significantly shorter for the flanged IOL fixation than for sutured SF (19.4 ± 4.6 vs. 48.9 ± 5.2 min, p < 0.001). BCVA in both groups improved at 1, 3, 6, and 12 months postoperatively (p < 0.05). BCVA in the 2 groups was similar during the 12 months of observation. The refractive difference, IOL tilt, IOL decentration, and incidence of postoperative complications were also not different in the 2 groups. Conclusion: Sutured SF and flanged IOL fixation had similar visual outcomes and IOL stability in patients with IOL dislocation. However, the operating time for flanged IOL fixation was less than half that of the sutured SF. This technique is an efficient alternative for treating IOL dislocation. [ABSTRACT FROM AUTHOR]

Background: Four commercial porcine reproductive and respiratory syndrome virus (PRRSV) modified‐live vaccines (MLV) was compared to protect growing pigs against dual challenge of PRRSV‐1 and PRRSV‐2. Methods: Two of the vaccines were based on PRRSV‐1, and two on PRRSV‐2. A total of 72 PRRSV‐naïve pigs were divided into six groups (12 pigs/group). Results: Two PRRSV‐1 MLV‐vaccinated and two PRRSV‐2 MLV‐vaccinated groups reduced significantly (p <.05) genomic copies of PRRSV‐1 in their sera compared to the unvaccinated challenged group. Two PRRSV‐2 MLV‐vaccinated groups reduced significantly (p <.05) fewer genomic copies of PRRSV‐2 in their sera whereas two PRRSV‐1 MLV‐vaccinated groups were unable to reduce genomic copies of PRRSV‐2 compared to unvaccinated challenged groups. Two PRRSV‐1 MLV‐vaccinated groups induced a stronger PRRSV‐1 specific IFN‐γ‐SC response, while two PRRSV‐2 MLV‐vaccinated groups induced a stronger PRRSV‐2 specific IFN‐γ‐SC response. Two PRRSV‐2 MLV‐vaccinated groups showed significantly (p <.05) lower mean macroscopic and microscopic lung lesion scores compared to two PRRSV‐1 MLV‐vaccinated groups. Conclusions: These data demonstrated that two PRRSV‐2 vaccines were efficacious and exhibited similar protection while, two PRRSV‐1 vaccines were largely ineffective against the dual challenge. [ABSTRACT FROM AUTHOR]

The current study examined the effects of different types of instructor comments on student engagement in an online discussion. In particular, this study examined three comment types: (1) praise-oriented comments, agreeing with students' initial messages and recapping their ideas, (2) elaboration-encouraging comments, requesting elaboration on the initial messages, and (3) perspective-widening comments, suggesting different or thought-provoking opinions responding to the initial messages. Seventeen graduate students enrolled in an online course were recruited. A content analysis was employed to evaluate the levels of knowledge construction. Interactivity was measured by the number of posts and idea units. The findings revealed that perspective-widening comments facilitated students' evaluation on the peer postings and brought up diverse perspectives, contributing to knowledge construction. While elaboration-encouraging comments led to high interactivity among students, praise-oriented comments had no significant effect on the frequency of interactivity. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate intraoperative complications and utilization of adjunctive devices between microscope and intracameral illuminations during cataract surgery in the elderly over 75 years. Design. A retrospective, consecutive, interventional case series Participants. Two hundred eighty-six eyes of 184 patients older than 75 years who underwent cataract surgery using microscope and intracameral illuminations. Methods. A chart review was performed on an advanced cataract surgery group of 141 consecutive cases in which the intracameral illumination was used and on a standard cataract surgery group of 145 consecutive cases in which the intracameral illumination was not used. Main Outcome Measures. Intraoperative complications (posterior capsule rupture, radial tear of the anterior capsule, dropped nucleus, or sulcus-implanted/sclera-fixated IOL) and utilization of adjunctive devices (pupil expansion device or anterior capsule staining). Results. The frequency of use of the pupil expansion device was lower in the advanced cataract surgery group than that in the standard cataract surgery group (0.7% vs 6.9%; p=0.007). Furthermore, the rates of a posterior capsule rupture and at least one intraoperative complication were lower in the advanced cataract surgery group than those in the standard cataract surgery group (0.7% vs 4.8%; p=0.067) (0.7% vs 7.6%; p=0.004). Conclusions. In the current cohort of patients over 75 years, the rate of intraoperative complications was lower when using the intracameral illumination than that when using the conventional method. Cataract surgery using intracameral illumination would be good option for elderly people. [ABSTRACT FROM AUTHOR]

Unconverted character was found in the following captions in B boldface b : Figure 2 "B5-agar plates containing 1 M DPI" should be "B5-agar plates containing 1 B µ b M DPI" Figure 3 "B5-agar plates containing 1 M DPI" should be "B5-agar plates containing 1 B µ b M DPI" Figure 4 "B5-agar plates containing 1 M DPI with or without 0.1 M NAA" should be "B5-agar plates containing 1 B µ b M DPI with or without 0.1 B µ b M NAA' Figure 4 "B5-agar plates containing 1 M DPI" should be "B5-agar plates containing 1 B µ b M DPI" Figure 7 "EGTA with or without 0.1 M NAA" should be "EGTA with or without 0.1 B µ b M NAA" The correction do not affect the Conclusions of the article. Wound-induced signals regulate root organogenesis in Arabidopsis explants. [Extracted from the article]

Objective Dentin sialophosphoprotein ( Dspp ) is expressed in odontoblasts and transiently expressed in early ameloblasts. However, the origin of Dspp in ameloblasts remains unclear. Our previous studies demonstrated that copine-7 (CPNE7), a molecule that is secreted by the dental epithelium, is expressed in early ameloblasts and is then translocated to differentiating odontoblasts; its expression levels correlate with odontoblast differentiation under the control of Dspp expression. The objective of this study is to figure out the relationship between CPNE7 and Dspp during amelogenesis. Design The gene expression patterns of CPNE7 and dentin sialoprotein (DSP) were examined by immunohistochemistry, western blot analysis, and real-time polymerase chain reaction. The effects of CPNE7 on Dspp regulation were investigated using luciferase and chromatin immunoprecipitation assays in ameloblastic HAT-7 cells. Results The gene expression pattern of Cpne7 was similar to that of Dspp during ameloblast differentiation. Moreover, Gene expression omnibus profiles indicated that there is a close correlation between Cpne7 and Dspp expression in various normal human tissues. We also confirmed the effects of CPNE7 on the induction of Dspp in ameloblastic HAT-7 cells. Cpne7 overexpression promoted Dspp expression, whereas Dspp expression was down-regulated by Cpne7 inactivation. Conclusions These results suggest that the expression of Dspp in early amelogenesis is linked to CPNE7, a preameloblast-derived factor. [ABSTRACT FROM AUTHOR]

Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared with HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice. Of note, substitution of the PB2 gene segment of the H5N8 virus by that from the H5N1 virus resulted in a 1000-fold increase in virulence for mice compared with the parental virus (MLD50 decreased from 105.8 to 102.5 EID50). Further, the W452W149PB2 virus also induced the highest virus titers in lungs at all time points and the highest levels of inflammatory cytokine responses among all viruses tested. This high virulence phenotype was also confirmed by high viral titers in the respiratory tracts of infected ferrets. Further, a mini-genome assay revealed that W452W149PB2 has significantly increased polymerase activity (p < 0.001). Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. Methodology/Principal findings: In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. Conclusions/Significance: Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia. [ABSTRACT FROM AUTHOR]

During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. [ABSTRACT FROM AUTHOR]

A Gram-negative, short rod-shaped, gliding motile, and pale pink-pigmented bacterial strain, designated 15J9-9, was isolated from the soil of Iho Tewoo Beach, Jeju Island, Korea, and characterized taxonomically using a polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that strain 15J9-9 belonged to the family Cytophagaceae and was related to Larkinella bovis M2T2B15 (96.5% similarity), Larkinella arboricola Z0532 (95.3% similarity), and Larkinella insperata LMG 22510 (95.2% similarity). The DNA G+C content of strain 15J9-9 was 48 mol%. The detection of phosphatidylethanolamine, phosphatidylserine, two unknown aminophospholipids (APL and APL), and two unknown polar lipids (L and L) in polar lipid profile, menaquinone-7 as the predominant quinone, and a fatty acid profile of C ω5 c, iso-C, and iso-C 3-OH as the major fatty acids supported the affiliation of strain 15J9-9 to the genus Larkinella. Based on its phenotypic properties and phylogenetic distinctiveness, strain 15J9-9 should be classified in the genus Larkinella as a representative of a novel species, for which the name Larkinella harenae sp. nov. is proposed. The type strain is 15J9-9 (=KCTC 42999 = JCM 31656). [ABSTRACT FROM AUTHOR]

To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10–40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD 50 of H5N8 virus, with the exception of mice vaccinated with 3.5 μg of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. [ABSTRACT FROM AUTHOR]

This paper describes the conversion of Ni Nd and Ni Tb compartment compounds into 1D coordination polymers or discrete tetranuclear 3 d –4 f compounds under microwave-heating conditions. Stirring a water–ethanol solution containing Ni(CH 3 COO) 2 ·4H 2 O, o -vanillin, 1,3-diaminopropane and LiOH·H 2 O at 30 °C produced [Ni(L 1 ) 2 ](H 2 O) ( 1 ), which possesses two imine–amine type ligands (HL 1 = ((3-methoxysalicylidene)amino)-3-aminopropane). Compound 1 reacted with Nd(NO 3 ) 3 ·6H 2 O to give a dinuclear Ni Nd complex [NiNd(HL 1 ) 2 (NO 3 ) 3 ](NO 3 ) 2 ( 2 ). When compound 2 was microwave-heated (700 W) in water in the presence of a bispyridine (bipy = 4,4′-bipyridine; bipp = 1,3-bis(4-pyridyl)propane), a tetranuclear dimer bridged by two nitrato (NO 3 − ) ligands was obtained: [NiNd(L 2 )(NO 3 )( μ 3 -NO 3 )(bipy)] 2 (OH) 2 (H 2 O) 2 (bipy) or [NiNd(L 2 )(NO 3 )( μ 3 -NO 3 )(bipp)] 2 (OH) 2 (H 2 O) 4 (H 2 L 2 = 1,3-bis((3-methoxysalicylidene)amino)propane). By contrast, compound 2 was converted into a 1D coordination polymer, [Ni 2 Nd 2 (L 2 ) 2 (H 2 O) 2 ( μ -NO 3 ) 3 ](OH − ) 3 (H 2 O) 6 , when microwave-heated in the absence of the bispyridine. Compound 1 reacted with Tb(NO 3 ) 3 ·5H 2 O to give a dinuclear complex [NiTb(HL 1 ) 2 (NO 3 ) 3 ]·(NO 3 ) 2 , a Ni Tb analogue of compound 2 . Microwave-heating this Ni Tb compound in water and in acetonitrile produced a 1D coordination polymer, [Ni 2 Tb 2 (L 2 ) 2 ( μ -NO 3 ) 3 (H 2 O) 2 ]·(OH − ) 3 ·4H 2 O, and a tetranuclear Ni Tb dimer, [NiTb(L 2 )( μ 3 -NO 3 )(NO 3 )(H 2 O)] 2 ·(OH) 2 ·(H 2 O) 4 , respectively. The Ni Tb compounds exhibited emission quenching of the Tb 3+ ion, probably due to a Tb 3+ → Ni 2+ energy transfer. In addition, the intensities of the emission spectra of these compounds did not increase when the lattice water molecules were removed. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations. We quantified global leukocytes and lymphocyte subpopulations of peripheral blood from 37 NF1 patients and 21 healthy controls by flow cytometry. To associate immune phenotype with tumor phenotype, all NF1 patients underwent whole-body magnetic resonance imaging and total internal tumor volume was calculated. The immunophenotypes were compared among four NF1 groups with different total internal tumor burdens and between NF1 patients and non-NF1 subjects. We found that NF1 patients show a generalized lymphopenia. Closer analysis revealed that the CD8/CD27 and CD8/CD57 effector T cell fractions strongly increase in NF1 patients with low tumor load and decrease to levels below control in patients with high tumor load. Moreover, increased production of IL2, IFN-γ and TNF-α was found in T cells of NF1 patients upon phorbol-12-myristate acetate (PMA) stimulation compared to healthy controls. The data indicate that decreasing CD8/CD57 and CD27 T cell fractions correspond to increasing tumor load in NF1 patients, potentially making these populations useful marker for internal tumor burden. [ABSTRACT FROM AUTHOR]

The article presents an experimental study on development of a method for purity assignment of L-Valine amino acid by a mass balance method. Topics discussed include study of L-Valine purity assignment by quantitative-nuclear magnetic resonance (Q-NMR), determination of water content in the L-valine sample by 851 Titrando Karl-Fisher coulometer and analysis of impurities in the L-valine sample high performance liquid chromatography (HPLC)-diode array detector.

The purpose of this study is to investigate the effects of euphorbiasteroid, a component of Euphorbia lathyris L., on adipogenesis of 3T3-L1 pre-adipocytes and its underlying mechanisms. Euphorbiasteroid decreased differentiation of 3T3-L1 cells via reduction of intracellular triglyceride (TG) accumulation at concentrations of 25 and 50 μM. In addition, euphorbiasteroid altered the key regulator proteins of adipogenesis in the early stage of adipocyte differentiation by increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, levels of adipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α, were decreased by euphorbiasteroid treatment at the late stage of adipocyte differentiation. The anti-adipogenic effect of euphorbiasteroid may be derived from inhibition of early stage of adipocyte differentiation. Taken together, euphorbiasteroid inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway. Therefore, euphorbiasteroid and its source plant, E. lathyris L., could possibly be one of the fascinating anti-obesity agent. [ABSTRACT FROM AUTHOR]

Cadmium zinc telluride (CZT)-based small-animal single-photon emission computed tomography (SPECT) has desirable characteristics such as superior energy resolution, but data acquisition for SPECT imaging has been widely performed with a conventional energy window. The aim of this study was to determine the optimal energy window settings for technetium-99 m ( 99m Tc) and thallium-201 ( 201 Tl), the most commonly used isotopes in SPECT imaging, using CZT-based small-animal SPECT for quantitative accuracy. We experimentally investigated quantitative measurements with respect to primary count rate, contrast-to-noise ratio (CNR), and scatter fraction (SF) within various energy window settings using Triumph X-SPECT. The two ways of energy window settings were considered: an on-peak window and an off-peak window. In the on-peak window setting, energy centers were set on the photopeaks. In the off-peak window setting, the ratios of energy differences between the photopeak from the lower- and higher-threshold varied from 4:6 to 3:7. In addition, the energy-window width for 99m Tc varied from 5% to 20%, and that for 201 Tl varied from 10% to 30%. The results of this study enabled us to determine the optimal energy windows for each isotope in terms of primary count rate, CNR, and SF. We selected the optimal energy window that increases the primary count rate and CNR while decreasing SF. For 99m Tc SPECT imaging, the energy window of 138–145 keV with a 5% width and off-peak ratio of 3:7 was determined to be the optimal energy window. For 201 Tl SPECT imaging, the energy window of 64–85 keV with a 30% width and off-peak ratio of 3:7 was selected as the optimal energy window. Our results demonstrated that the proper energy window should be carefully chosen based on quantitative measurements in order to take advantage of desirable characteristics of CZT-based small-animal SPECT. These results provided valuable reference information for the establishment of new protocol for CZT-based small-animal study, and may offer insights into the potential of multiple-isotope imaging with CZT-based small-animal SPECT. [ABSTRACT FROM AUTHOR]

Asthma and atopic dermatitis are common allergic diseases, and their prevalence has increased in urban children. Recently, it is becoming understood that forest environment has favorable health effects in patients with chronic diseases. To investigate favorable clinical and immunologic effects of forest, we examined changes in clinical symptoms, indirect airway inflammatory marker, and serum chemokines before and after a short-term forest trip. The forest trips were performed with 21 children with asthma and 27 children with atopic dermatitis. All participating children were living in air polluted urban inner-city. We measured spirometry and fractional exhaled nitric oxide (FeNO) in children with asthma and measured scoring atopic dermatitis (SCORAD) index and Thymus and Activation-Regulated Chemokine (TARC)/CCL17 and Macrophage-Derived Chemokine (MDC)/CCL22 levels in children with atopic dermatitis before and after the forest trip. Indoor air pollutants such as indoor mold, particulate matter 10 (PM10) and total volatile organic compounds (TVOCs) of each child's home and the accommodations within forest were measured. A significant increase in forced vital capacity (FVC) and a significant decrease in FeNO were observed after the forest trip in children with asthma. SCORAD indices and MDC/CCL22 levels were significantly decreased after the forest trip in children with atopic dermatitis. Airborne mold and PM10 levels in indoor were significantly lower in the forest accommodations than those of children's homes; however, TVOC levels were not different between the two measured sites. Short-term exposure to forest environment may have clinical and immunological effects in children with allergic diseases who were living in the urban community. [ABSTRACT FROM AUTHOR]

In P seudomonas aeruginosa, quorum sensing ( QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, T enebrio molitor as a host model, we found that Protease IV, a QS-regulated exoprotease of P . aeruginosa functions as a key virulence effector causing the melanization and death of T . molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme ( SPE) and SPE-activating enzyme ( SAE) without the activation of the antimicrobial peptide ( AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T . molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted T enebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P . aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs. [ABSTRACT FROM AUTHOR]

The present study examined the in vitro activity of various antibiotics including zabofloxacin, against isolates responsible for invasive pneumococcal diseases. Between 1997 and 2008, a total of 208 isolates were collected from sterile fluids, including blood ( n = 196, 94.2%), pleural fluid ( n = 5, 2.4%), cerebrospinal fluid ( n = 5, 2.4%), and ascites ( n = 2, 1.0%). Zabofloxacin showed the lowest MIC 50 (0.015 μg/mL) and MIC 90 (0.025 μg/mL) values of all the tested antibiotics. Rates of isolates resistant to penicillin (MIC ≥8 μg/mL), ceftriaxone (MIC ≥4 μg/mL) and levofloxacin (MIC ≥8 μg/mL) were 3.4%, 0.4% and 2.0%, respectively. Four isolates (2.0%) were resistant to levofloxacin, and zabofloxacin showed low MICs (range, 0.025–0.125 μg/mL). Zabofloxacin shows potent in vitro activity against S. pneumoniae isolates that caused invasive disease, even strains that are resistant to levofloxacin. [ABSTRACT FROM AUTHOR]

Background and Aim Of the Study: Total anomalous pulmonary venous connection (TAPVC) is a rare cyanotic congenital heart defect. This study aimed to evaluate the outcome of isolated TAPVC repairs and the prognoses of affected patients in the last 12 years at a single center.Methods: We retrospectively analyzed the medical records of 51 patients who underwent isolated TAPVC repair from 2007 to 2018.Results: The median age at operation was 19 days, and the median body weight was 3.3 kg. Thirteen (25.5%) patients had emergency operations, and the median follow-up period was 29.54 ± 36.77 months. Early mortality was noted in five patients and late mortality was noted in one patient. Pulmonary vein stenosis was observed in 22 patients within 3 to 6 months after the operation, and six patients required reoperation or transcatheter interventions. Low birth weight, small left atrial volume, long operation time, and preoperative heart failure were identified as risk factors for mortality.Conclusions: Isolated TAPVC can rapidly lead to hemodynamic instability during the neonatal period and is associated with high mortality rates. Increasing the prenatal diagnosis rate and stabilizing the patients' condition before the operation are considered important for improving the surgical outcome. [ABSTRACT FROM AUTHOR]

Exosomal miRNAs have been studied in various cancers as minimally invasive biomarkers. This study aimed to investigate the potential of exosomal microRNAs (miRNAs) as biomarkers for esophageal squamous cell carcinoma (ESCC). Exosomes were isolated from cultures of esophageal epithelial cell and ESCC cell lines using ExoDisc, and exosomal miRNAs were detected via miRNA sequencing. Of the differentially expressed 14 miRNAs, the top 2 up-regulated miRNAs (miR-205-5p and miR-429) and top 2 down-regulated miRNAs (miR-375-3p and miR-483-3p) were selected as ESCC target miRNAs. Four selected exosomal miRNAs were validated in the plasma of 20 healthy controls (HCs) and 40 ESCC patients via quantitative reverse transcription-polymerase chain reaction. The expression of plasma exosomal miR-205-5p and miR-429 significantly increased, while that of plasma exosomal miR-375-3p was significantly reduced in ESCC patients compared to that in HCs. At cut-off values of 5.04, 2.564, and 0.136, the sensitivity and specificity for the diagnosis of ESCC were 72.5% and 70.0% for miR-205-5p, 60.0% and 60.0% for miR-429, and 65.0% and 65.0% for miR-375-3p, respectively. Based on the exosomal miRNAs identified in ESCC cell lines, our study demonstrated that plasma exosomal miR-205-5p, miR-429, and miR-375-3p could serve as potential biomarkers for ESCC diagnosis. [ABSTRACT FROM AUTHOR]

Ta metal is frequently used as a raw material in the production of military hardware and electromagnetic components; therefore, obtaining high-purity tantalum is emerging as an important goal. Here, Ta metal powder was successfully prepared by reduction of Mg gas with tantalum pentoxide (Ta 2 O 5). The reduction behavior was studied kinetically using Ta 2 O 5 with different initial particle sizes (0.3 and 1.2 μm). Reduction temperature varied in the range from 1073 to 1273 K. In the X-ray diffraction patterns of reduced powders, pure Ta peaks appear above 1123 K when using the 0.3 μm initial powder, and at 1173 K when using the 1.2 μm initial powder. With increasing reduction temperature, reduction rates were higher with the use of the 0.3 μm powder than with the coarser 1.2 μm powder. This behavior resulted in different activation energies for Mg-reduction (5.234 and 8.695 kJ/mol for the 0.3 and 1.2 μm powder, respectively). In the powder reduced at 1273 K, the oxygen content was lowered to 0.66 and 0.88 wt% for the 1.2 and 0.3 μm powders, respectively; this is explained by differences in the specific surface area according to particle size. • Metallic tantalum powder was prepared by reduction of Mg gas with Ta 2 O 5. • Reduction behavior varied with initial Ta 2 O 5 particle size (0.3 vs. 1.2 μm). • Pure tantalum formed above 1123 K (1173 K) using 0.3-μm (1.2-μm) initial powder. • Reduction rate (Mg activation energy) was higher (lower) for 0.3-μm powder. • Oxygen content higher for 0.3-μm powder reflecting different specific surface area. [ABSTRACT FROM AUTHOR]

Most HIV-positive individuals diagnosed in Korea are infected through sexual contact, with the time of HIV infection therefore often being unknown. The aim of this study was to investigate the characteristics of diagnosed patients near the time of HIV seroconversion to establish useful HIV intervention strategies. Cross-sectional study. Newly diagnosed HIV cases based on the national HIV surveillance system in South Korea, 2008–2015. To distinguish recent from long-standing HIV infection among 5898 nationwide HIV-positive specimens, limiting antigen avidity assays (Sedia HIV-1 LAg-Avidity EIA, cut-off = 1.5) were performed. Data on CD4+ T cell count at HIV diagnosis and death from AIDS within one year after first HIV diagnosis were used to distinguish recent HIV infections. Acute HIV infection is characterized by detectable HIV RNA or HIV p24 antigen levels, along with a negative or indeterminate antibody western blot result, but with the subject subsequently testing positive after a predetermined period. We analyzed the characteristics of recent and acute HIV infections by sex, age, nationality, HIV testing site, region, and reason for HIV testing. Recent and acute HIV infections were described as the proportion of recent and acute HIV infections among newly-diagnosed cases in a given year. Recent and acute HIV infections over the 8-year study period were 20.5% (1210/5898) and 9.5% (562/5898), respectively. Both infections were generally higher in the following groups: males, younger age, Koreans, individuals who were tested due to disease, residents of smaller city or rural area, and individuals diagnosed in recent calendar years. Acute infections were significantly higher among individuals tested in hospitals and due to suspected HIV infection. The recent and acute HIV infection in younger age groups (< 30 years) has been increasing in a given year. There was an increase in the proportion of young individuals with recent HIV infection, and we identified risk groups more at risk of HIV infection recently in Korea. Therefore, our results could prove useful for the development and assessment of national HIV prevention strategies in Korea and provide valuable data for further HIV research. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS)-based intact mass analysis and structural characterization of biotherapeutic proteins such as monoclonal antibodies (mAbs) are a crucial characterization approach from upstream drug development to downstream product analysis. Due to various endogenous modifications leading to the structural heterogeneity and several N-linked glycan species resulting in macro-heterogeneity, it is challenging to characterize the mAbs. Hence, it is essential to understand the micro-heterogeneity of such proteins with high level of complexity which may vary in charge, size, or hydrophobicity. The development of high-throughput native separation techniques hyphenated with MS with high sensitivity and excellent mass accuracy has improved the top/middle down analysis, intact mass detection, subunit analysis, enhanced sequence coverage, and accurate localization of site-specific modifications. In this review, we have focused on the critical inroads taken for the improvement in MS-based techniques to resolve the challenges related to analysis of mAbs. Various MS-based techniques and their role in high-order structural analysis and the progress in software development have been explained, and further, the challenges remaining have been discussed. [ABSTRACT FROM AUTHOR]

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age‐related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7‐null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7‐derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin‐pulp complex lined with metabolically active odontoblasts is observed in 23‐month‐old Cpne7‐overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7‐overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease‐targeted applications, especially age‐related dental diseases involving dentinal loss. [ABSTRACT FROM AUTHOR]

Simple Summary: Increasing demand for an efficient and economic fishmeal feed for sustainable aquaculture has urged the aquafeed sector to seek an optimum fish-feed formulation. This study investigated the physiological response in olive flounder fed various fishmeal diets in a typical fish farm. The fish were farmed for 20 weeks, using the following experimental feeds: a control feed (CON), a replacement by 20% (F20), and 30% (F30) of the fish meal content of the CON. All groups showed no significant difference in growth and survival rates. However, due to investigating hormone expression associated with maturation, high expression of PSS-I and low expression of FSH-β, ER-α, and ER-β in FM30 compared to other experimental groups were observed. Therefore, up to 30% fishmeal replacement does not affect growth, but it appears to have a slight effect on the sexual development of olive flounder. Olive flounder (Paralichthys olivaceus) is a commercially important and valuable species for aquaculture in Korea. Due to the unstable supply of fishmeal for farmed fish, an optimum fish-feed formulation should be researched to ensure the sustainability of P. olivaceus aquaculture. This study investigated the effect of three experimental diets: Con (basal diet); FM20 (20% fishmeal replacement of CON); and FM30 (30% fishmeal replacement of CON) on P. olivaceus over 20 weeks at a typical farm by monitoring the growth and factors relating to sexual maturation. The results showed that no differences in growth were observed between the CON and diet-replacement groups. Gonadal oocyte development was similar between the CON and diet-replacement groups. Moreover, sbGnRH and GH expression did not differ between the CON and diet-replacement groups. The levels of Erβ and Vtg expression were significantly higher in the FM20 group than in the CON and FM30 groups after the experimental period. The expression of PSS-I was significantly higher in the FM30 group than in the CON and FM20 groups. Therefore, although growth occurred when 30% of the fishmeal was replaced, such high dietary protein replacement may be ill-advised during the maturation of olive flounder at the commercial fish farm. [ABSTRACT FROM AUTHOR]

Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012–2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00–7.99 log 10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5–8 log 10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5–8 log 10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points. [Display omitted] • A new HCC risk prediction score was developed in patients entering into HBeAg-positive CHB from chronic infection. • PAGED-B score incorporated moderate HBV DNA levels and diabetes status into the original PAGE-B score. • PAGED-B score predicted the 5-year risk of HCC with high accuracy. [ABSTRACT FROM AUTHOR]

Introduction: SB12 is a biosimilar to eculizumab reference product [SolirisTM (Soliris is a trademark of Alexion Pharmaceuticals, Inc.)] that acts as a C5 complement protein inhibitor. The infusion stability of in-use (diluted) SB12 outside the conditions stated in the reference product's label is unknown. Objective: The objective of this study was to assess the stability of SB12 after extended storage in conditions not claimed in the originator label. Methods: Infusion stability was assessed in SB12 samples (diluted in 0.9% NaCl, 0.45% NaCl, and 5% dextrose, final concentration of 5 mg/mL per clinical trial protocol and the reference product's label) kept at 5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% relative humidity (RH) for 72 h. The product was stored in different containers [polyolefin (PO) bags, glass bottles and syringes], and the protocol followed International Conference on Harmonisation (ICH) and European Medicines Agency (EMA) requirements for stability evaluation of biological products. Stability was evaluated using complementary assays, including pH, protein concentration (A280), purity (size exclusion-high-performance liquid chromatography, capillary electrophoresis-sodium dodecyl sulfate, and imaged capillary isoelectric focusing), biological activity (C5 binding and inhibition), and safety (subvisible particles). Results: Except for charge variants in SB12 diluted in 5% dextrose, all results met the stability acceptance criteria. There were no major changes in terms of physicochemical stability, biological activity, and subvisible particles. Conclusions: The infusion stability of SB12 after extended storage (5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% RH for 72 h) was demonstrated for longer periods and at higher temperatures than what is stated in the EU and US labels of the reference product. The physicochemical properties, biological activity, and subvisible particles of in-use SB12 diluted in 0.9% NaCl and 0.45% NaCl were maintained under the described conditions and for all tested containers. However, instability was observed for the diluted SB12 in 5% dextrose. These results may reduce the workload of clinical staff and minimize drug waste from treatment delays without any loss in product quality and biological activity. [ABSTRACT FROM AUTHOR]

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare aggressive sarcomas with poor prognosis. More than half of MPNSTs develop from benign precursor tumors associated with neurofibromatosis type 1 (NF1) which is a tumor suppressor gene disorder. Early detection of malignant transformation in NF1 patients is pivotal to improving survival. The primary aim of this study was to evaluate the role of immuno-modulators as candidate biomarkers of malignant transformation in NF1 patients with plexiform neurofibromas as well as predictors of response to immunotherapeutic approaches. Methods: Sera from a total of 125 NF1 patients with quantified internal tumor load were included, and 25 of them had MPNSTs. A total of six immuno-modulatory factors (IGFBP-1, PD-L1, IFN-α, GM-CSF, PGE-2, and AXL) were measured in these sera using respective ELISA. Results: NF1 patients with MPNSTs had significantly elevated PD-L1 levels in their sera compared to NF1 patients without MPNSTs. By contrast, AXL concentrations were significantly lower in sera of NF1-MPNST patients. IGFBP-1 and PGE2 serum levels did not differ between the two patient groups. IFN-α and GM-CSF were below the detectable level in most samples. Conclusion: The immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

The current experimental study examined the effects of graphic organizers in a collaborative learning context where students constructed knowledge during online discussions. As the results could vary depending on how students interacted with the graphic organizers, this study compared two different approaches: instructor-provided versus student-generated graphic organizers. Thus, the purpose of this study was to investigate the effects of receiving or generating graphic organizers on students’ engagement in online discussions. Thirty-six graduate students enrolled in an online graduate course participated in the study. While analyzing an instructional design case, students were asked to discuss design issues in a randomly assigned group. There were three conditions: control condition without graphic organizers, instructor-provided, and student-generated graphic organizers. Major findings revealed that both generating and receiving graphic organizers facilitated students’ higher levels of cognitive engagement, and encouraged students to consider alternative views during the discussions. Without the graphic organizer, students tended to simply summarize previous messages or raise new issues rather than elaborating on previous topics. There was a significant finding regarding the ways of interacting graphic organizers. Students discussed more topics when they were given instructor’s graphic organizers rather than when they were asked to generate them. [ABSTRACT FROM AUTHOR]

Introduction: SB11 (Byooviz™) is a ranibizumab biosimilar that acts as a vascular endothelial growth factor (VEGF)-A inhibitor. Stability data for unopened SB11 vials at room temperature are limited and no data are available for SB11 withdrawn into syringes (in-use) for intravitreal administration. Methods: SB11 stability was assessed in two different settings: unopened vials stored at 30 ± 2 °C/65 ± 5% relative humidity (RH) for 2 months, and in-use SB11 withdrawn into syringes stored at 5 ± 3 °C for 98 days and then 25 ± 2 °C/60 ± 5% RH for 24 h. The product was stored in the absence of light, and the experimental design followed International Conference on Harmonization and European Medicines Agency requirements for stability evaluation of biological products. Analysis included visual appearance (color, clarity, and presence of visible particles), pH, protein concentration (A280) and purity (size-exclusion high-pressure liquid chromatography, capillary electrophoresis–sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity (VEGF binding and neutralization), and safety (sub-visible particulates). Results: Except for charge variants in unopened vials at room temperature after 1 month by US standards, all results met the stability acceptance criteria (US and EU) for both unopened vials and for in-use SB11. There were no major changes in terms of physicochemical stability, biological activity and sub-visible particulates. Conclusion: SB11 was stable for longer periods and at higher temperatures than what is stated in the labels of the reference product (Lucentis) and SB11. The physicochemical properties, biological activity, and sub-visible particulates of SB11 in both tested settings (unopened vials at room temperature and in-use product withdrawn into syringes) were maintained under the described storage periods. This information can help to avoid unnecessary delays in patient treatment without any loss in quality and biological activity, lower the workload of health care providers and reduce costs associated with drug waste. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether a signal alteration (SA) in the optic nerve head (ONH) on 3D T2-weighted magnetic resonance imaging (MRI) is associated with glaucomatous optic neuropathy Materials and Methods: A total of 35 patients with bilateral open-angle glaucoma and 31 age-matched controls underwent 3D high-resolution (0.98 × 0.98 × 1 mm3) T2-weighted MRI and detailed ophthalmologic examinations including spectral-domain optical coherence tomography (OCT). Two independent reviewers blinded to subject data determined mild or prominent SA on 3D T2-weighted MRI for the incomplete or complete loss of ocular hypointense continuity in the ONH, respectively. The prevalence of SAs was compared between the two groups with the chi-square test. The OCT measurements were compared among the eyes with a mild or prominent SA and those without an SA using the Kruskal–Wallis test. Results: Of the 35 eyes with glaucoma, 26 eyes (74.3%) exhibited an SA in the ONH, whereas it was observed in 5 (16.1%) of the 31 controls (P < 0.001). The eyes with a prominent SA had a significantly different average retinal nerve fiber layer thickness (P = 0.002) and the ONH parameters except for the disk area (allP < 0.001) than those without an SA. The eyes with a mild SA had a significantly narrower neural rim area, larger cup volume, and larger average and vertical cup-to-disk ratios compared with those without an SA (P = 0.011, 0.003, 0.004, and 0.004, respectively) Conclusions: The SA in the ONH on 3D T2-weighted MRI was significantly more frequent in eyes with open-angle glaucoma than in the controls. [ABSTRACT FROM PUBLISHER]

Background: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. Objective: To evaluate the anti‐photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB‐irradiated hairless mice. Methods: SKH‐1 hairless mice were exposed to UVB irradiation (30–60 mJ/cm2), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer, and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) was analyzed by immunoblotting. Results: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB‐irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. Conclusion: Based on results for our study, APEE or APWE could protect the UVB‐mediated skin wrinkle and is new target for the developing anti‐wrinkle cosmetics. [ABSTRACT FROM AUTHOR]

Plant cells in damaged tissue can be reprogrammed to acquire pluripotency and induce callus formation. However, in the aboveground organs of many species, somatic cells that are distal to the wound site become less sensitive to auxin-induced callus formation, suggesting the existence of repressive regulatory mechanisms that are largely unknown. Here we reveal that submergence-induced ethylene signals promote callus formation by releasing post-transcriptional silencing of auxin receptor transcripts in non-wounded regions. We determined that short-term submergence of intact seedlings induces auxin-mediated cell dedifferentiation across the entirety of Arabidopsis thaliana explants. The constitutive triple response 1-1 (ctr1-1) mutation induced callus formation in explants without submergence, suggesting that ethylene facilitates cell dedifferentiation. We show that ETHYLENE-INSENSITIVE 2 (EIN2) post-transcriptionally regulates the abundance of transcripts for auxin receptor genes by facilitating microRNA393 degradation. Submergence-induced calli in non-wounded regions were suitable for shoot regeneration, similar to those near the wound site. We also observed submergence-promoted callus formation in Chinese cabbage (Brassica rapa), indicating that this may be a conserved mechanism in other species. Our study identifies previously unknown regulatory mechanisms by which ethylene promotes cell dedifferentiation and provides a new approach for boosting callus induction efficiency in shoot explants. In this study, the authors find that submerging intact seedlings promotes auxin-induced callus formation in shoot explants. Short-term submergence activates EIN2-dependent ethylene signaling, which promotes miR393 degradation. This process induces accumulation of the transcripts encoding TIR1/AFB2 auxin receptors, resulting in enhanced auxin responses. These findings provide a potential method for breaking dormancy in cell dedifferentiation and for boosting callus induction efficiency during tissue culture. [ABSTRACT FROM AUTHOR]

Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses. [ABSTRACT FROM AUTHOR]

To investigate the molecular changes that allow influenza B viruses to adapt to new mammalian hosts, influenza B/Florida/04/2006 was serially passaged in BALB/c mice until highly virulent. The viral factors underlying this transition were then investigated in mice and ferrets. Five viruses, including the wild-type virus (P0), three intermediate viruses (P5, P9, and P12), and a lethal mouse-adapted virus (P17 (MA)), harbored one to five amino acid substitutions in the hemagglutinin, M, NP, and PA segments suggesting that these mutations enhance virulence. The P17 (MA) virus replicated significantly more efficiently than the P0 virus both in vitro and in vivo (P < 0.0001), and was highly virulent (MLD50: 105.25TCID50) while the P0, P5, and P9 viruses did not kill any infected mice (MLD50 > 106.0TCID50). Furthermore, the P17 (MA) virus grew to greater titers in the ferret upper respiratory tract compared with the P0 and intermediate viruses, and only the P17 (MA) virus was transmissible between ferrets via both direct and aerosol contact. To our knowledge, this is the first study to demonstrate ferret-to-ferret transmission of influenza B virus and to delineate factors that may affect its transmission. [ABSTRACT FROM AUTHOR]

For clinical applications of cells and tissue engineering products it is of importance to characterize the quality of the used cells in detail. Progenitor cells from the periosteum are already routinely applied in the clinics for the regeneration of the maxillary bone. Periosteal cells have, in addition to their potential to differentiate into bone, the ability to develop into cartilage and fat. However, the question arises whether all cells isolated from periosteal biopsies are able to differentiate into all three tissue types, or whether there are subpopulations. For an efficient and approved application in bone or cartilage regeneration the clarification of this question is of interest. Therefore, 83 different clonal cultures of freshly isolated human periosteal cells derived from mastoid periosteum biopsies of 4 donors were generated and growth rates calculated. Differentiation capacities of 51 clonal cultures towards the osteogenic, the chondrogenic, and the adipogenic lineage were investigated. Histological and immunochemical stainings showed that 100% of the clonal cultures differentiated towards the osteogenic lineage, while 94.1% demonstrated chondrogenesis, and 52.9% could be stimulated to adipogenesis. For osteogenesis real-time polymerase chain reaction (PCR) of BGLAP and RUNX2 and for adipogenesis of FABP4 and PPARG confirmed the results. Overall, 49% of the cells exhibited a tripotent potential, 45.1% showed a bipotent potential (without adipogenic differentiation), 3.9% bipotent (without chondrogenic differentiation), and 2% possessed a unipotent osteogenic potential. In FACS analyses, no differences in the marker profile of undifferentiated clonal cultures with bi- and tripotent differentiation capacity were found. Genome-wide microarray analysis revealed 52 differentially expressed genes for clonal subpopulations with or without chondrogenic differentiation capacity, among them DCN, NEDD9, TGFBR3, and TSLP. For clinical applications of periosteal cells in bone regeneration all cells were inducible. For a chondrogenic application a fraction of 6% of the mixed population could not be induced. [ABSTRACT FROM AUTHOR]

(Na1− xK x)NbO3 (NKN) nanorods with an orthorhombic (OR) structure, a rhombohedral (RH) structure, or a polymorphic phase (PP) structure, which contains both OR and RH structures, are prepared. The presence of RH and PP NKN nanorods is explained by the existence of OH− defects at the O2− sites of the NKN nanorods. The PP NKN nanorods grown on a Nb5+-doped SrTiO3 substrate show the largest piezoelectric strain constant of 175 pm/V because they have more directions for dipole rotation than OR and RH NKN nanorods. Piezoelectric nanogenerators (NGs) are synthesized using composites consisting of NKN nanorods with various structures and polydimethylsiloxane. The largest open-circuit output voltage is 35 V, and the short-circuit current is 5.0 μA, which are obtained using the NG containing 0.7 g of PP NKN nanorods. Moreover, this NG shows a maximum output power of 16.5 μW for an external load of 10.0 MΩ. [ABSTRACT FROM AUTHOR]