Deep-learning-based attenuation map generation in kidney single photon emission computed tomography.

BACKGROUND: Accurate attenuation correction (AC) is vital in nuclear medicine, particularly for quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. This study aimed to establish a CT-free quantification technology in kidney SPECT imaging using deep learning to generate synthetic attenuation maps (µ-maps) from SPECT data, thereby reducing radiation exposure and eliminating the need for CT scans. RESULTS: A dataset of 1000 Tc-99m DTPA SPECT/CT scans was analyzed for training (n = 800), validation (n = 100), and testing (n = 100) using a modified 3D U-Net for deep learning. The study investigated the use of primary emission and scattering SPECT data, normalization methods, loss function optimization, and up-sampling techniques for optimal µ-map generation. The problem of checkerboard artifacts, unique to µ-map generation from SPECT signals, and the effects of iodine contrast media were evaluated. The addition of scattering SPECT to primary emission SPECT imaging, logarithmic maximum normalization, the combination of absolute difference loss (L1) and three times the absolute gradient difference loss (3 × LGDL), and the nearest-neighbor interpolation significantly enhanced AI performance in µ-map generation (p < 0.00001). Checkerboard artifacts were effectively eliminated using the nearest-neighbor interpolation technique. The developed AI algorithm produced µ-maps neutral to the presence of iodine contrast and showed negligible contrast effects on quantitative SPECT measurement, such as glomerular filtration rate (GFR). The potential reduction in radiation exposure by transitioning to AI-based CT-free SPECT imaging ranges from 45.3 to 78.8%. CONCLUSION: The study successfully developed and optimized a deep learning algorithm for generating synthetic µ-maps in kidney SPECT images, demonstrating the potential to transition from conventional SPECT/CT to CT-free SPECT imaging for GFR measurement. This advancement represents a significant step towards enhancing patient safety and efficiency in nuclear medicine.

CCCP induces hepatic stellate cell activation and liver fibrogenesis via mitochondrial and lysosomal dysfunction.

Hepatic stellate cells (HSCs) are primary cells for development and progression of liver fibrosis. Mitophagy is an essential lysosomal process for mitochondrial homeostasis, which can be activated by carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a representative mitochondrial uncoupler. However, little information is available on the role of CCCP-mediated mitophagy in HSC activation and liver fibrogenesis. In this study, we showed that CCCP treatment in HSCs caused mitochondrial dysfunction proved by decreased mitochondrial membrane potential, mitochondrial DNA, and ATP contents and increased mitochondrial ROS. Moreover, CCCP induced mitophagy and impaired mitophagy flux at the later stage. This blockade of mitophagic flux effect was mediated by suppression of lysosomal activity; CCCP decreased expression of lysosomal markers and cathepsin B activity, and increased lysosomal pH. Intriguingly, CCCP treatment in LX-2 cells or primary HSCs elevated plasminogen activator inhibitor-1 (PAI-1), a typical fibrogenic marker of HSCs which was attenuated by mitochondrial division inhibitor 1, a mitophagy inhibitor. The up-regulation of PAI-1 by CCCP was not due to altered transcriptional activity but lysosomal dysfunction. In vivo acute or sub-chronic treatment of CCCP to mice induced mitophagy and fibrogenesis of liver. Hepatic fibrogenic marker (PAI-1) was incremented with mitophagy markers (parkin and PTEN-induced putative kinase 1) in the livers of CCCP injected mice. Furthermore, we found that 5-aminoimidazole-4-carboxyamide ribonucleoside reversed CCCP-mediated mitophagy and subsequent HSC activation. To conclude, CCCP facilitated HSC activation and hepatic fibrogenesis via mitochondrial dysfunction and lysosomal blockade, implying that attenuation of CCCP-related signaling molecules may contribute to treat liver fibrosis.

Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Reactive Oxygen Species-Responsive Chitosan-Bilirubin Nanoparticles Loaded with Statin for Treatment of Cerebral Ischemia.

Cerebral ischemia impairs blood circulation, leading to elevated reactive oxygen species (ROS) production. A ROS-responsive delivery of drugs can enhance the therapeutic efficacy and minimize the side effects. There is insufficient evidence on the impact of ROS-responsive nanoparticles on ischemic stroke. We developed ROS-responsive chitosan-bilirubin (ChiBil) nanoparticles to target acute ischemic lesions and investigated the effect of atorvastatin-loaded ROS-responsive ChiBil. We randomly assigned rats with transient middle cerebral artery occlusion (MCAO) to 4 groups: saline, Statin, ChiBil, and ChiBil-Statin. These groups were treated daily via the tail vein for 7 d. Behavioral assessment, magnetic resonance (MR) imaging, evaluation of neuroinflammation, blood-brain barrier (BBB) integrity, apoptosis, and neurogenesis after stroke were conducted. In vitro, results showed nanoparticle uptake and reduced intracellular ROS, lipid peroxidation, and inflammatory cytokines (IL-6 and TNF-α). In vivo, results showed improved motor deficits and decreased infarct volumes on MR images in the ChiBil-Statin group compared with the Control group on day 7 (P < 0.05). Furthermore, the expression of inflammatory cytokines such as IL-1ß and IL-6 was reduced in the ChiBil-Statin group compared with the Control group (P < 0.05). Improvements in BBB integrity, apoptosis, and neurogenesis were observed in the ChiBil-Statin group. The findings demonstrated that intravenous ROS-responsive multifunctional ChiBil-Statin could effectively deliver drugs to the ischemic brain, exerting marked synergistic pleiotropic neuroprotective effects. Therefore, ChiBil-Statin holds promise as a targeted therapy for ischemic vascular diseases characterized by increased ROS production, leading to new avenues for future research and potential clinical applications.

PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src.

Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.

METTL18 functions as a Phenotypic Regulator in Src-Dependent Oncogenic Responses of HER2-Negative Breast Cancer.

Methyltransferase-like (METTL)18 has histidine methyltransferase activity on the RPL3 protein and is involved in ribosome biosynthesis and translation elongations. Several studies have reported that actin polymerization serves as a Src regulator, and HSP90 is involved in forming polymerized actin bundles. To understand the role of METTL18 in breast cancer and to demonstrate the importance of METTL18 in HER-2 negative breast cancer metastasis, we used biochemical, molecular biological, and immunological approaches in vitro (breast tumor cell lines), in vivo (tumor xenograft model), and in samples of human breast tumors. A gene expression comparison of 31 METTL series genes and 22 methyltransferases in breast cancer patients revealed that METTL18 is highly amplified in human HER2-negative breast cancer. In addition, elevated levels of METTL18 expression in patients with HER2-negative breast cancer are associated with poor prognosis. Loss of METTL18 significantly reduced the metastatic responses of breast tumor cells in vitro and in vivo. Mechanistically, METTL18 indirectly regulates the phosphorylation of the proto-oncogene tyrosine-protein kinase Src and its downstream molecules in MDA-MB-231 cells via METTL18-mediated RPL3 methylation, which is also involved in determining HSP90 integrity and protein levels. In confocal microscopy and F/G-actin assays, METTL18 was found to induce actin polymerization via HSP90. Molecular events involving METTL18, RPL3, HSP90, and actin polymerization yielded Src phosphorylated at both tyrosine 419 and tyrosine 530 with kinase activity and oncogenic functions. Therefore, it is suggested that the METTL18-HSP90-Actin-Src regulatory axis plays critical oncogenic roles in the metastatic responses of HER2-negative breast cancer and could be a promising therapeutic target.

An inducible sphingosine kinase 1 in hepatic stellate cells potentiates liver fibrosis.

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-ß (TGF-ß)-treated LX-2 cells. TGF-ß-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-ß-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-ß facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.

Development of a biomarker-based platform for comprehensive skin characterization using minimally invasive skin sampling and quantitative real-time PCR.

BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.

Focused magnetic stimulation for motor recovery after stroke.

BACKGROUND AND OBJECTIVES: The effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. METHODS: We randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. RESULTS: The Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1ß, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. CONCLUSIONS: Focused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

Development of AI-generated medical responses using the ChatGPT for cancer patients.

BACKGROUND AND OBJECTIVE: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients. METHODS: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024. RESULTS: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores). CONCLUSIONS: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Is Renal Denervation Effective in Treating Resistant Hypertension?

Resistant hypertension is diagnosed in patients whose blood pressure target is unmet despite the use of three or more antihypertensive medications. Systemic sympathetic hyperactivation is associated with the development of resistant hypertension. As the kidney is largely pervasive of the sympathetic nervous system renal denervation procedure was developed to control blood pressure by attenuating the renal and systemic sympathetic hyperactivity. Renal denervation is a minimally invasive procedure that uses radiofrequency or ultrasound energy waves to reduce the activity of the renal artery nerves. Previous clinical trials have shown conflicting results regarding the efficacy of the procedure. Symplicity HTN-1 and -2 trials showed effective blood pressure lowering results in the renal denervation group with a good safety profile. However, the Symplicity HTN-3 trial showed no difference in blood pressure lowering effect between the renal denervation and control Sham procedure groups. Notwithstanding, some recent clinical trials with Sham control and meta-analysis showed clinical benefits of renal denervation. Other clinical benefits of renal denervation include glucose control, cardiovascular protective effect, reduction of obstructive sleep apnea, and neuralgia control. A subset of patients with satisfactory blood pressure control response to the procedure may experience improved glucose control due to the overall reduced sympathetic activity and insulin resistance. Sympathetic activity control after renal denervation has cardioprotective effects, especially for those with arrhythmia and left ventricular hypertrophy. Also, renal denervation could be helpful in renalorigin pain control. Renal denervation is an effective, safe, non-invasive procedure with many clinical benefits beyond blood pressure control. Further development in the procedure technique and selection of target patients are needed for wider clinical use of renal denervation in resistant hypertension.

Mortality of elderly patients with acute kidney injury undergoing continuous renal replacement therapy: is age a risk factor?

BACKGROUND: Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. METHODS: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65-74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. RESULTS: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99-1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30-0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18-10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02-2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36-0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28- day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. CONCLUSION: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

[MR Imaging Features of Pediatric Bone Marrow]. / 소아 골수의 MR 영상 소견.

MRI plays a crucial role in bone marrow (BM) assessment, and has very high sensitivity in diagnosing marrow disorders. However, for radiologists who may not frequently encounter pediatric imaging, distinguishing pathologic BM lesion from normal BM can be challenging. Conditions involving the BM in pediatric patients, such as leukemia and metastatic neuroblastoma, often manifest with diverse musculoskeletal symptoms and may be diagnosed using musculoskeletal MRI examinations. Accurate interpretation of pediatric MRI requires not only an understanding of the normal composition of BM but also an awareness of agerelated developmental changes in the marrow and familiarity with conditions that commonly involve pediatric BM. We aim to describe the composition of normal BM and outline the normal and abnormal MRI findings in pediatric BM. Additionally, we aim to present clinical cases of malignant BM disorders including leukemia, neuroblastoma metastasis, and other malignant BM disorders.

Family-based genome-wide association analysis of novelty seeking in a Korean schizophrenic population: A pilot study.

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.

Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization.

Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay. Mexenone suppressed the LPS-induced downregulation of junctional proteins and phosphorylation of VE-cadherin in Bovine Aortic Endothelial Cells (BAECs). The injection of mexenone 1 hr before LPS administration completely blocked LPS-induced lung vascular permeability and acute lung injury in mice after 18hr. Our results suggest that mexenone-induced endothelial cell (EC) barrier stabilization could be effective in treating sepsis patients.

Characteristics of patients and facility of peritoneal dialysis in Korea: Results from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) Korea.

BACKGROUND: Varying peritoneal dialysis (PD)-related clinical outcomes have been reported in different countries. As a participant of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), this study investigated the characteristics of Korean PD patients, PD facilities and the incidence rates of clinical outcomes including mortality and PD-related outcomes. METHODS: From July 2019 to December 2021, a total of 766 Korean PD patients were included for analysis. Poisson regression analysis was used to explore the incidence rates of various clinical events including mortality, modality transfer, exit site or catheter tunnel infection and peritonitis. RESULTS: Among the 766 patients (median age 55.5 years, males 59.5%), 276 were incident and 490 were prevalent PD patients. The incidence rates of events were as follows: all-cause mortality (0.048), modality transfer (0.051), exit site or catheter tunnel infection (0.054) and peritonitis (0.136) events per person year. The most common causative organism for exit site or tunnel infection was staphylococcus species (47%) and that for peritonitis was streptococcus (28%) followed by staphylococcus (27%) species. CONCLUSIONS: Up to now, PDOPPS Korea has recruited 766 Korean PD patients and started documentation of major PD-related outcomes which occurred during the follow-up period. The overall incidence rates of clinical outcomes in Korean PD patients were relatively favourable. There was no statistically significant difference in the incidence rates of clinical outcomes according to both facility and patient factors.

Alteration of Keratinized Mucosa Dimensions in the Early Healing Period after Implant Placement: A 6-month Prospective Study.

PURPOSE: This study aimed to assess the alteration in keratinized mucosa (KM) dimensions in the early healing period after implant placement, and the influence of variables obtained during implant surgery on KM alteration. MATERIALS AND METHODS: Study participants were consecutively recruited from patients who had received implants following a non-submerged surgical protocol. The implant had to be installed in the extraction socket that had healed for more than 6 months without any soft or hard tissue augmentation. Keratinized mucosa width (KMW), keratinized mucosa thickness (KMT), soft tissue level (STL), and probing pocket depth (PPD) were measured at implant placement and 3 and 6 months after implant surgery. The influence of variables obtained during implant surgery on the 6-month KMW alteration was assessed. RESULTS: A total of 66 implants in 55 patients who completed the follow-up examination after 6 months were included in this study. KMW, KMT, and STL significantly decreased at 3- and 6-months examination by 0.7-1.2 mm. KMW was reduced by 24.6%. Mesial PPD significantly increased between the 3- and 6-months follow-up. In the multivariate generalized estimating estimations analysis, the implant diameter negatively influenced the 6-month KMW alteration, but the KMW at implant surgery positively influenced the 6-month KMW alteration. CONCLUSIONS: The KMW decreased significantly at 3 and 6 months after implant placement. If the initial KMW was wider, the KMW was reduced more at 6 months after implant placement. Therefore, it is important to carefully monitor KMW alterations during the early healing period to ensure optimal esthetics and peri-implant tissue health.

In vitro Fertilization Outcomes of Frozen-thawed Embryo Transfer with Hatched Blastocysts versus with Hatching Blastocysts.

This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.

Interface of gallium-based liquid metals: oxide skin, wetting, and applications.

Gallium-based liquid metals (GaLMs) are promising for a variety of applications-especially as a component material for soft devices-due to their fluidic nature, low toxicity and reactivity, and high electrical and thermal conductivity comparable to solid counterparts. Understanding the interfacial properties and behaviors of GaLMs in different environments is crucial for most applications. When exposed to air or water, GaLMs form a gallium oxide layer with nanoscale thickness. This "oxide nano-skin" passivates the metal surface and allows for the formation of stable microstructures and films despite the high-surface tension of liquid metal. The oxide skin easily adheres to most smooth surfaces. While it enables effective printing and patterning of the GaLMs, it can also make the metals challenging to handle because it adheres to most surfaces. The oxide also affects the interfacial electrical resistance of the metals. Its formation, thickness, and composition can be chemically or electrochemically controlled, altering the physical, chemical, and electrical properties of the metal interface. Without the oxide, GaLMs wet metallic surfaces but do not wet non-metallic substrates such as polymers. The topography of the underlying surface further influences the wetting characteristics of the metals. This review outlines the interfacial attributes of GaLMs in air, water, and other environments and discusses relevant applications based on interfacial engineering. The effect of surface topography on the wetting behaviors of the GaLMs is also discussed. Finally, we suggest important research topics for a better understanding of the GaLMs interface.