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Pathogenic water molds have a significant impact on many species, especially amphibians. The genus Saprolegnia is a pathogenic oomycete restricted to aquatic and moist habitats, and its presence is strongly linked to the abundance of amphibians and fishes. We investigated the influence of Saprolegnia presence on egg mortality and egg occurrence under varying environmental conditions in the Asiatic toad Bufo gargarizans at 27 breeding sites in the Republic of Korea. We then assessed the impact of Saprolegnia on the presence of B. gargarizans at the 27 sites surveyed weekly during the B. gargarizans breeding season for 3 consecutive years. We used molecular tools to identify the water molds as belonging to an undescribed S. ferax strain. We demonstrated that the presence of S. ferax was positively associated with higher water conductivity and ponds. In addition, while S. ferax prevalence was associated with a reduction in B. gargarizans breeding activity and breeding success, we could not determine its impact on the subsequent breeding seasons. Our study highlights the potential negative effects of Saprolegnia on amphibian reproduction, although additional research is necessary to determine the relationship between Saprolegnia, its hosts and the impacts of habitat loss on amphibians.
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Bufonidae , Saprolegnia , Animais , Fungos , Infecções , República da CoreiaRESUMO
AIMS: The clinical relevance of expression of chemokine receptor 4 (CXCR4) in colorectal carcinoma (CRC) remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. METHODS AND RESULTS: A meta-analysis was performed. Original data included the hazard ratios (HRs) of recurrence-free survival (RFS), overall survival (OS) and odds ratio (OR) in CRC patients. We pooled HR/OR with 95% confidence intervals (CIs) to estimate the hazard. A total of 20 published studies (including 2253 patients) were eligible. RFS and OS were related significantly to CXCR4 expression, with HRs 1.62 (95% CI 1.24-2.11; P < 0.0001) and 1.68 (95% CI 1.31-2.14; P < 0.0001), respectively. In addition, a significant association was revealed between positive CXCR4 expression and age (less than median age: OR 0.78, 95% CI 0.62-0.98; P = 0.03), stage (I and II: OR 0.46, 95% CI 0.32-0.66; P < 0.0001), grade (well/moderately differentiated: OR 0.74, 95% CI 0.56-0.98; P = 0.04), location (colon: OR: 0.73, 95% CI 0.57-0.95; P = 0.02), lymph node invasion (present: OR2.14, 95% CI 1.36-3.37; P = 0.001),and distant metastasis (present: OR 2.40; 95% CI 1.36-4.23; P = 0.003). Heterogeneity was observed among the included studies with regard to stage (I(2) = 58 %), lymph node invasiveness (I(2) = 74%) and distant metastasis (I(2) = 56%). No publication bias was observed. CONCLUSIONS: Chemokine receptor 4 expression indicates poorer prognosis in older patients and advanced stage or poor differentiation in CRC, and also serves as an indicator of lymph node and distal organ metastasis. Surprisingly, high CXCR4 expression may indicate that the location of the tumour is the rectum. Thus, CXCR4 could help to predict outcome and guide clinical therapy.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices.
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Aprovação de Equipamentos , Estados Unidos , República da Coreia , Aprovação de Equipamentos/legislação & jurisprudência , Humanos , Europa (Continente) , Equipamentos e Provisões , União Europeia , United States Food and Drug Administration , Legislação de Dispositivos MédicosRESUMO
Although thermal tolerance along geographical gradients gives an insight into species' response to climate change, current studies on thermal tolerance are strongly skewed towards global-scale patterns. As a result, intraspecific variations are often assumed to be constant, despite a lack of evidence. To understand population-specific responses to thermal stress, we investigated the presence of intraspecific variations in the critical thermal maximum (CTmax) of tadpoles in two anuran species, Rana uenoi and Bufo sachalinensis. The study was conducted across a five-degree latitudinal gradient in the Republic of Korea. We exposed the tadpoles to increasing temperatures and recorded the CTmax for 270 R. uenoi individuals from 11 sites, collected in rice paddies, and for 240 B. sachalinensis individuals from ten sites, collected in reservoirs. We also recorded the swimming performance and behavior of the tadpoles when placed in an experimental apparatus during CTmax measurements. We then used linear regressions to determine the relationship between abiotic factors and CTmax. In R. uenoi, we found a positive relationship between latitude and CTmax, but the tadpoles did not display specific thermoregulatory behaviors. In B. sachalinensis, none of the abiotic factors such as climate and geographic coordinates were related to CTmax, but we detected a tendency to swim close to the water surface when water temperature was increasing. For R. uenoi, we tentatively relate the CTmax variability across the latitudinal gradient to a physiological adaptive response associated with habitat characteristics that are assumed to be fluctuating, as the species inhabits small water bodies prone to drying out. In the case of B. sachalinensis, the behavior observed may be linked to oxygen depletion and thermoregulation, as it may buffer temperature changes in the absence of physiological adjustment. These findings suggest that intra-specific variations in CTmax are greater than generally accounted for, and thermal conditions of natural environments are important for understanding thermal tolerance in ectothermic species. Our results highlight that species' specific responses to climate warmings need to be studied to better protect species against climate change.
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Species biodiversity organises along elevational trends and is generally expected to decrease with increasing elevation. This pattern is regulated by numerous factors, although principally overridden by temperature in ectotherms such as amphibians. Here, we collated elevation data (n = 55,182) collected between 1909 and 2020. We then determined elevation distribution patterns and species communities for all amphibians in the Republic of Korea. Species were found to range from sea level up to 1,393 m a.s.l. The average elevational distribution was significantly different between species but also between anura and caudata. On average, anura were found at lower elevations with a peak in species richness and abundance matching with the lowlands. In opposition, the peak in species richness and abundance for caudata matched with low hilly landscapes. The altitudinal distributions of species were strongly skewed, with all 23 species found within the 0-199 m range, and steadily decreasing with only five species within the last elevational range (1,200-1,399 m). Finally, only a few species were found below 30 m, reflecting a likely risk of salinisation in this environment. Our results help understand the altitudinal distribution of amphibians in the Republic of Korea.
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The resistive switching behavior of the solution processed SiOx device was investigated by inserting TiO2 nanoparticles (NPs). Compared to the pristine SiOx device, the TiO2 NPs inserted SiOx (SiOx@TiO2 NPs) device achieves outstanding switching characteristics, namely a higher ratio of SET/RESET, lower operating voltages, improved cycle-to-cycle variability, faster switching speed, and multiple-RESET states. Density functional theory calculation (DFT) and circuit breaker simulation (CB) were used to detail the origin of the outstanding switching characteristic of the SiOx@TiO2 NPs. The improvement in resistive switching is mainly based on the difference in formation/rupture of the conductive path in the SiO2 and SiO2@TiO2 NPs devices. In particular, the reduction of resistance and lower switching voltage of TiO2 NPs control the formation and rupture of the conductive path to achieve more abrupt switching between SET/RESET with higher on/off ratio. This method of combined DFT calculation and CB offers a promising approach for high-performance non-volatile memory applications.
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TiOx-based resistive switching devices have recently attracted attention as a promising candidate for next-generation non-volatile memory devices. A number of studies have attempted to increase the structural density of resistive switching devices. The fabrication of a multi-level switching device is a feasible method for increasing the density of the memory cell. Herein, we attempt to obtain a non-volatile multi-level switching memory device that is highly transparent by embedding SiO2 nanoparticles (NPs) into the TiOx matrix (TiOx@SiO2 NPs). The fully transparent resistive switching device is fabricated with an ITO/TiOx@SiO2 NPs/ITO structure on glass substrate, and it shows transmittance over 95% in the visible range. The TiOx@SiO2 NPs device shows outstanding switching characteristics, such as a high on/off ratio, long retention time, good endurance, and distinguishable multi-level switching. To understand multi-level switching characteristics by adjusting the set voltages, we analyze the switching mechanism in each resistive state. This method represents a promising approach for high-performance non-volatile multi-level memory applications.
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Determining the range, status, ecology and behaviour of species from areas where surveys and samplings are uncommon or difficult to conduct is a challenge, such as in the Democratic People's Republic of Korea (DPR Korea). Here, we used genetic samples, field surveys, call recordings, photographic identification and a literature review to estimate the presence, range and status of amphibians in the DPR Korea. From our combined results and based on the IUCN Red List categories and criteria, we were able to estimate the national threat levels for most species. Our results demonstrated the presence of 18 native species and the suspected presence of Karsenia koreana and two Onychodactylus species. We reported the first record for Rana uenoi in the vicinity of Pyongyang using molecular tools and similarly confirmed the presence of Dryophytes japonicus at the same location. Based on distribution and modelling, we can expect the contact zone between species within the Rana and Onychodactylus genera to be located along the Changbai Massif, a mountain range that marks a shift in ecoregions and acts as a barrier to dispersion. The species richness was higher in the lowlands and at lower latitudes, with such areas populated by up to 11 species, while more northern regions were characterised by species richness of about half of that value. The combination of ecological models and known threats resulted in the recommendation of ten species as threatened at the national level following the IUCN Red List categories and criteria. This high number of threatened species was anticipated based on the high threat level to amphibians in bordering nations and globally. While the ecology of species in the DPR Korea is still understudied, we argue that species relying on agricultural wetlands such as rice paddies are not under imminent threat due to the enduring presence of extensive agricultural landscapes with low rates of chemical use and mechanisation. The maintenance of such landscapes is a clear benefit to amphibian species, in contrast to more industrialised agricultural landscapes in neighbouring nations. In comparison, the status of species dependent on forested habitats is unclear and threat levels are likely to be higher because of deforestation, as in neighbouring nations.
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We evaluated the change in the chemical structure between dielectrics (AlOx and HfOx) grown by atomic layer deposition (ALD) and oxidized black phosphorus (BP), as a function of air exposure time. Chemical and structural analyses of the oxidized phosphorus species (PxOy) were performed using atomic force microscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, first-principles density functional theory calculations, and the electrical characteristics of field-effect transistors (FETs). Based on the combined experiments and theoretical investigations, we clearly show that oxidized phosphorus species (PxOy, until exposed for 24 h) are significantly decreased (self-reduction) during the ALD of AlOx. In particular, the field effect characteristics of a FET device based on Al2O3/AlOx/oxidized BP improved significantly with enhanced electrical properties, a mobility of â¼253 cm2 V-1 s-1 and an on-off ratio of â¼105, compared to those of HfO2/HfOx/oxidized BP with a mobility of â¼97 cm2 V-1 s-1 and an on-off ratio of â¼103-104. These distinct differences result from a significantly decreased interface trap density (Dit â¼ 1011 cm-2 eV-1) and subthreshold gate swing (SS â¼ 270 mV dec-1) in the BP device caused by the formation of stable energy states at the AlOx/oxidized BP interface, even with BP oxidized by air exposure.