Background/Aims: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods: Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.1, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30). Conclusions: TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.
Evaluation of the test performance of the Target enhanced whole-genome sequencing (TE-WGS) assay for comprehensive oncology genomic profiling. The analytical validation of the assay included sensitivity and specificity for single nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs), revealing a revealed a sensitivity of 99.8% for SNVs and 99.2% for indels. The positive predictive value (PPV) was 99.3% SNVs and 98.7% indels. Clinical validation was benchmarked against established orthogonal methods and demonstrated high concordance with reference methods. TE-WGS provides insights beyond targeted panels by comprehensive analysis of key biomarkers and the entire genome encompassing both germline and somatic findings.
The historical climate variability in East Antarctica inferred from ice cores remains under debate owing to the vastness and complexity of the region. This study evaluates the potential climate variabilities in the Styx-M ice core records (δ18O, d-excess, and snow accumulation) from northern Victoria Land adjacent to the Ross Sea sector of East Antarctica during 1979-2014. Results show that the primary moisture source in this area is the Pacific Ocean sector. Although the annual mean δ18O values was limited to directly indicate the temperature changes, a weak relevance between the average δ18O values and the temperature signal during the austral summer season is detectable. δ18O, d-excess, and snow accumulation correlate with sea surface temperature and sea ice extent in the Ross Sea sector. A coupled influence of the SAM, ASL, and ENSO climate indices is expected, because the oceanic environment in this region is influenced by them. The pronounced intrusion of oceanic moisture coupled with atmospheric circulation patterns over the Ross Sea region makes the Styx-M ice core a promising record of the local oceanic conditions, with the snow accumulation rate being a direct proxy. Additionally, the analysis of trace elements from 1979 to 1999 revealed the presence of crustal dust sourced from the Transantarctic Mountains, as well as non-crustal sources, both intricately linked with atmospheric transport. These results demonstrate that the contributions of-and variations in-oceanic conditions associated with atmospheric circulation changes are detectable and dominant in the Styx-M ice core. This study serves as a basis for interpreting longer parts of the Styx-M ice core.
(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: L. muscari extract significantly reduces biofilm formation by 51.65% at 1.56 µg/mL use and therefore increases susceptibility to miconazole. L. muscari extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 µg/mL of the extract was treated. The extract of L. muscari inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 µg/mL of L. muscari extract treatment; (4) Conclusions: L. muscari extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that L. muscari extract is a promising anti-biofilm candidate of Candida albicans since the biofilm formation of Candida albicans is an excellent target for candidiasis regulation.
To better understand the changes in the hydrologic cycle caused by global warming in Antarctica, it is crucial to improve our understanding of the groundwater flow system, which has received less attention despite its significance. Both hydraulic and thermal properties of the active layer, through which groundwater can flow during thawing seasons, are essential to quantify the groundwater flow system. However, there has been insufficient information on the Antarctic active layer. The goal of this study was to estimate the hydraulic and thermal properties of Antarctic soils through laboratory column experiments and inverse modeling. The column experiments were conducted with sediments collected from two lakes in the Barton Peninsula, Antarctica. A sand column was also operated for comparison. Inverse modeling using HydroGeoSphere (HGS) combined with Parameter ESTimation (PEST) was performed with data collected from the column experiments, including permeameter tests, saturation-drain tests, and freeze-thaw tests. Hydraulic parameters (i.e., Ks, θs, Swr, α, ß, and Ss) and thermal diffusivity (D) of the soils were derived from water retention curves and temperature curves with depth, respectively. The hydraulic properties of the Antarctic soil samples, estimated through inverse modeling, were 1.6 × 10-5-3.4 × 10-4 cm s-1 for Ks, 0.37-0.42 for θs, 6.62 × 10-3-1.05 × 10-2 for Swr, 0.53-0.58 cm-1 for α, 5.75-7.96 for ß, and 5.11 × 10-5-9.02 × 10-5 cm-1 for Ss. The thermal diffusivities for the soils were estimated to be 0.65-4.64 cm2 min-1. The soil hydraulic and thermal properties reflected the physical and ecological characteristics of their lake environments. The results of this study can provide a basis for groundwater-surface water interaction in polar regions, which is governed by variably-saturated flow and freeze-thaw processes.
Until now, bacteria able to degrade, 3,3'-iminodipropionitrile (IDPN), a neurotoxin that destroys vestibular hair cells, causing ototoxicity, culminating in irreversible movement disorders, had never been isolated. The aim of this study was to isolate a novel IDPN-biodegrading microorganism and characterize its metabolic pathway. Enrichment was performed by inoculating activated sludge from a wastewater treatment bioreactor that treated IDPN-contaminated wastewater in M9 salt medium, with IDPN as the sole carbon source. A bacterial strain with a spherical morphology that could grow at high concentrations was isolated on a solid medium. Growth of the isolated strain followed the Monod kinetic model. Based on the 16S rRNA gene, the isolate was Paracoccus communis. Whole-genome sequencing revealed that the isolated P. communis possessed the expected full metabolic pathway for IDPN biodegradation. Transcriptome analyses confirmed the overexpression of the gene encoding hydantoinase/oxoprolinase during the exponential growth phase under IDPN-fed conditions, suggesting that the enzyme involved in cleaving the imine bond of IDPN may promote IDPN biodegradation. Additionally, the newly discovered P. communis isolate seems to metabolize IDPN through cleavage of the imine bond in IDPN via nitrilase, nitrile hydratase, and amidase reactions. Overall, this study lays the foundation for the application of IDPN-metabolizing bacteria in the remediation of IDPN-contaminated environments.
Biodegradation, Environmental , Bioreactors , Nitriles , Paracoccus , Waste Disposal, Fluid , Wastewater , Nitriles/metabolism , Paracoccus/metabolism , Paracoccus/genetics , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/metabolism , RNA, Ribosomal, 16S
Efforts are ongoing to enhance the functionality of human acellular dermal matrices (hADMs), which are extensively utilized in reconstructive surgeries. Among these efforts, plasma treatments, particularly vacuum plasma treatments, have recently emerged in the medical field. This study aims to investigate the efficacy of a vacuum plasma treatment in enhancing the biocompatibility and biointegration of hADMs. Utilizing a plasma activator (ACTILINK reborn, Plasmapp Co., Ltd., Daejeon, Republic of Korea), hADMs were treated and evaluated through in vitro and in vivo analyses. Hydrophilicity changes were gauged by the blood absorption times, while SEM imaging was used to analyze physical surface deformation. Protein adsorption was measured with fluorescently labeled bovine serum albumin and fibronectin. For the in vivo study, mice were implanted with plasma-treated and untreated hADMs, and the post-implantation effects were analyzed through histological and immunofluorescence microscopy. The plasma-treated hADMs demonstrated a significantly enhanced hydrophilicity compared to the untreated samples. SEM imaging confirmed the maintenance of the microroughness after the treatment. The treated hADMs showed a significant reduction in fibronectin adsorption, a critical factor for cellular adhesion. In vivo, the plasma-treated hADMs exhibited reduced capsule formation and enhanced fibroblast infiltration, indicating improved biocompatibility and integration. These findings highlight the potential of a plasma treatment to enhance the performance of hADMs in clinical settings, offering a promising avenue for improving reconstructive surgery outcomes.
BACKGROUND AND AIMS: No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. APPROACH AND RESULTS: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. CONCLUSIONS: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.
Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.
AIM: Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high-quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence. METHODS: Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time-varying effect of NA use on HCC recurrence was analyzed using various statistical methods. RESULTS: Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68-1.47; p = 1.00) by time-varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67-1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51-2.33; p = 0.82 for ETV). Kaplan-Meier analysis showed comparable HCC recurrence-free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time-varying Cox analyses in various subgroups confirmed the primary findings. CONCLUSIONS: TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.
Climate change can affect precipitation patterns, temperature, and the hydrological cycle, consequently influencing the dynamics of nitrogen (N) within aquatic ecosystems. In this study, multiple stable isotopes (15N-NO3/18O-NO3 and 2H-H2O/18O-H2O) were used to investigate the N sources and flowpath within the Bogang stream in South Korea. Within the vicinity of the stream with complex land use where various N sources were present, four end-members (rainfall, soil, sewage, and livestock) were sampled and examined. Consequently, spatial-temporal variations of the N sources were observed dependent on the type of land use. During the dry season, sewage accounted for the dominant N source, ranging from 62.2 % to 80.2 %. In contrast, nonpoint sources increased significantly across most sites during the wet season (10.3-41.6 % for soil; 6.3-35.2 % for livestock) compared to the dry season (7.7-28.5 % for soil; 6-13.2 % for livestock). However, sewage (78.7 %) remains dominant, representing the largest ratio at the site downstream of the wastewater treatment plant during the wet season. This ratio showed a notable difference from the calculated N loading ratio of 52.2 %, especially for livestock. This suggests that a significant potential for N legacy effects, given that groundwater flow is likely to be the primary hydrological pathway delivering N to rivers. This study will help to develop water resource management strategies by understanding how the interaction between N sources and hydrological process responds to climate change within sub-basins.
BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.
Hepatic Encephalopathy , Proton Pump Inhibitors , Humans , Male , Middle Aged , Gastrointestinal Hemorrhage/drug therapy , Hepatic Encephalopathy/etiology , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Proton Pump Inhibitors/adverse effects , Retrospective Studies , Risk Factors , Female
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
Liver Transplantation , Tissue and Organ Procurement , Humans , Asia , Liver , Liver Transplantation/methods , Living Donors
BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. METHODS: This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality. RESULTS: In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001). CONCLUSION: The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.
Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Cohort Studies , Overweight , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity/complications , Obesity/epidemiology
BACKGROUND/AIM: Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT). METHODS: We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1. RESULTS: A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74). CONCLUSION: The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.
RATIONALE: Electroconvulsive therapy (ECT) is an effective treatment modality for schizophrenia. However, its antipsychotic-like mechanism remains unclear. OBJECTIVES: To gain insight into the antipsychotic-like actions of ECT, this study investigated how repeated treatments of electroconvulsive seizure (ECS), an animal model for ECT, affect the behavioral and transcriptomic profile of a neurodevelopmental animal model of schizophrenia. METHODS: Two injections of MK-801 or saline were administered to rats on postnatal day 7 (PN7), and either repeated ECS treatments (E10X) or sham shock was conducted daily from PN50 to PN59. Ultimately, the rats were divided into vehicle/sham (V/S), MK-801/sham (M/S), vehicle/ECS (V/E), and MK-801/ECS (M/E) groups. On PN59, prepulse inhibition and locomotor activity were tested. Prefrontal cortex transcriptomes were analyzed with mRNA sequencing and network and pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) analyses were subsequently conducted. RESULTS: Prepulse inhibition deficit was induced by MK-801 and normalized by E10X. In M/S vs. M/E model, Egr1, Mmp9, and S100a6 were identified as center genes, and interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF) signaling pathways were identified as the three most relevant pathways. In the V/E vs. V/S model, mitophagy, NF-κB, and receptor for advanced glycation end products (RAGE) pathways were identified. qPCR analyses demonstrated that Igfbp6, Btf3, Cox6a2, and H2az1 were downregulated in M/S and upregulated in M/E. CONCLUSIONS: E10X reverses the behavioral changes induced by MK-801 and produces transcriptional changes in inflammatory, insulin, and mitophagy pathways, which provide mechanistic insight into the antipsychotic-like mechanism of ECT.
Antipsychotic Agents , Electroconvulsive Therapy , Schizophrenia , Rats , Animals , Dizocilpine Maleate/pharmacology , NF-kappa B , Schizophrenia/chemically induced , Schizophrenia/therapy , Antipsychotic Agents/pharmacology , Seizures/chemically induced , Seizures/metabolism
Background/Aims: : This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. Methods: : This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. Results: : In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). Conclusions: : Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Venous Thrombosis , Humans , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/complications , Liver Neoplasms/therapy , Prognosis , Retrospective Studies , Portal Vein/pathology , Chemoembolization, Therapeutic/methods , Treatment Outcome , Venous Thrombosis/complications , Venous Thrombosis/therapy
The necessity of reliable measurement data assessment in the realm of human life has experienced exponential growth due to its extensive utilization in health monitoring, rehabilitation, surgery, and long-term treatment. As a result, the significance of kinematic biosensors has substantially increased across various domains, including wearable devices, human-machine interaction, and bioengineering. Traditionally, the fabrication of skin-mounted biosensors involved complex and costly processes such as lithography and deposition, which required extensive preparation. However, the advent of additive manufacturing has revolutionized biosensor production by facilitating customized manufacturing, expedited processes, and streamlined fabrication. AM technology enables the development of highly sensitive biosensors capable of measuring a wide range of kinematic signals while maintaining a low-cost aspect. This paper provides a comprehensive overview of state-of-the-art noninvasive kinematic biosensors created using diverse AM technologies. The detailed development process and the specifics of different types of kinematic biosensors are also discussed. Unlike previous review articles that primarily focused on the applications of additively manufactured sensors based on their sensing data, this article adopts a unique approach by categorizing and describing their applications according to their sensing frequencies. Although AM technology has opened new possibilities for biosensor fabrication, the field still faces several challenges that need to be addressed. Consequently, this paper also outlines these challenges and provides an overview of future applications in the field. This review article offers researchers in academia and industry a comprehensive overview of the innovative opportunities presented by kinematic biosensors fabricated through additive manufacturing technologies.
The region around the tip of the Antarctic Peninsula is warming fast, a situation that will lead to widespread changes in local hydrological cycles. King George Island (KGI) hosts a complex network of lakes and rivers, fed by glaciers, snow and rain, and underlain by thick permafrost. We present here the first study of the stable isotope composition of the surface waters in the ice-free southern peninsulas of KGI. Permafrost samples had the highest δ18O and δ2H values (-6.7 and -50 , respectively), and river waters the lowest (-9.1 and -70 , respectively), with groundwater (-8.2 and -62.7 , respectively), lakes (-8.6 and -66.8 , respectively) and (summer) meltwater (-9 and -69.5 , respectively) having intermediary values. Our results suggest that a clear separation of the various water bodies (permafrost, snow, meltwater, lakes) based on the δ18Owater and δ2Hwater is possible. Further, water in lakes on a W-E transect (i.e. with increased distance from the Bellingshausen Sea) have a general tendency towards lower δ18O (and δ2H) values. The results allow for the establishment of a baseline against which ongoing and future changes of the hydrological cycle could be analysed, and past climate changes be reconstructed.
