Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.

Methylsulfonylmethane promotes melanogenesis via activation of JNK in Mel-Ab cells.

OBJECTIVE: Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is reported to be protective against certain skin disorders, but it is unknown whether it affects melanin synthesis. Therefore, in our current research, we examined the possibility of MSM controlling the production of melanin in Mel-Ab melanocytes. METHODS: In Mel-Ab cells, melanin contents and tyrosinase activities were assessed and quantified. The expression of microphthalmia-associated transcription factor (MITF) and tyrosinase was evaluated using western blot analysis, while MSM-induced signalling pathways were investigated. RESULTS: The MSM treatment significantly resulted in a dose-dependent increase in melanin production. Furthermore, MSM elevated melanin-related proteins, including MITF and tyrosinase. However, the rate-limiting enzyme of melanin production, tyrosinase, was not directly influenced by it. Therefore, we investigated potential melanogenesis-related signalling pathways that may have been triggered by MSM. Our findings showed that MSM did not influence the signalling pathways associated with glycogen synthase kinase 3ß, cAMP response-element binding protein, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. However, MSM phosphorylated c-Jun N-terminal kinases/stress-activated protein kinase (JNK/SAPK), which is known to induce melanogenesis. SP600125, a specific JNK inhibitor, inhibited MSM-induced melanogenesis. CONCLUSION: Taken together, our study indicates that MSM induces melanin synthesis and may serve as a therapeutic option for hypopigmentary skin disorders such as vitiligo.

The Effects of a Gate Bias Condition on 1.2 kV SiC MOSFETs during Irradiating Gamma-Radiation.

We investigated the effects of gate bias regarding the degradation of electrical characteristics during gamma irradiation. Moreover, we observed the punch through failure of 1.2 kV rated commercial Silicon Carbide (SiC) Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) due to the influence of gate bias. In addition, the threshold voltage (VT) and on-resistance (Ron) of the SiC MOSFETs decreased significantly by the influence of gate bias during gamma irradiation. We extracted the concentration of carriers and fixed charge (QF) in oxide using N-type SiC MOS capacitors and Transmission Line Measurement (TLM) patterns to analyze the effects of gamma irradiation. The Total Ionizing Dose (TID) effect caused by high-energy gamma-ray irradiation resulted in an increase in the concentration of holes and QF in both SiC and oxide. To analyze the phenomenon for increment of hole concentration in the device under gate bias, we extracted the subthreshold swing of SiC MOSFETs and verified the origin of TID effects accelerated by the gate bias. The QF and doping concentration of p-well values extracted from the experiments were used in TCAD simulations (version 2022.03) of the planar SiC MOSFET. As a result of analyzing the energy band diagram at the channel region of 1.2 kV SiC MOSFETs, it was verified that punch-through can occur in 1.2 kV SiC MOSFETs when the gate bias is applied, as the TID effect is accelerated by the gate bias.

Electrostatic [FeFe]-hydrogenase-carbon nitride assemblies for efficient solar hydrogen production.

The assembly of semiconductors as light absorbers and enzymes as redox catalysts offers a promising approach for sustainable chemical synthesis driven by light. However, achieving the rational design of such semi-artificial systems requires a comprehensive understanding of the abiotic-biotic interface, which poses significant challenges. In this study, we demonstrate an electrostatic interaction strategy to interface negatively charged cyanamide modified graphitic carbon nitride (NCNCNX) with an [FeFe]-hydrogenase possessing a positive surface charge around the distal FeS cluster responsible for electron uptake into the enzyme. The strong electrostatic attraction enables efficient solar hydrogen (H2) production via direct interfacial electron transfer (DET), achieving a turnover frequency (TOF) of 18 669 h-1 (4 h) and a turnover number (TON) of 198 125 (24 h). Interfacial characterizations, including quartz crystal microbalance (QCM), photoelectrochemical impedance spectroscopy (PEIS), intensity-modulated photovoltage spectroscopy (IMVS), and transient photocurrent spectroscopy (TPC) have been conducted on the semi-artificial carbon nitride-enzyme system to provide a comprehensive understanding for the future development of photocatalytic hybrid assemblies.

Photocatalytic CO2 Reduction Using Homogeneous Carbon Dots with a Molecular Cobalt Catalyst.

A simple and precious-metal free photosystem for the reduction of aqueous CO2 to syngas (CO and H2) is reported consisting of carbon dots (CDs) as the sole light harvester together with a molecular cobalt bis(terpyridine) CO2 reduction co-catalyst. This homogeneous photocatalytic system operates in the presence of a sacrificial electron donor (triethanolamine) in DMSO/H2O solution at ambient temperature. The photocatalytic system exhibits an activity of 7.7 ± 0.2 mmolsyngas gCDs -1 (3.6 ± 0.2 mmolCO gCDs -1 and 4.1 ± 0.1 mmolH2 gCDs -1) after 24 hours of full solar spectrum irradiation (AM 1.5G). Spectroscopic and electrochemical characterization supports that this photocatalytic performance is attributed to a favorable association between CDs and the molecular cobalt catalyst, which results in improved interfacial photoelectron transfer and catalytic mechanism. This work provides a scalable and inexpensive platform for the development of CO2 photoreduction systems using CDs.

Correction: Rheu et al. Effect of Fermented Sarco Oyster (Crassostrea gigas) Extract on Muscle Strength Enhancement in Postmenopausal Females: A Randomized, Double-Blind, Placebo-Controlled Trial. Int. J. Environ. Res. Public Health 2022, 19, 16450.

There was an error in the original publication [...].

Cardiovascular and Respiratory Effects of Increased Intra-Abdominal Pressure with and without Dexmedetomidine in Anesthetized Dogs.

Intra-abdominal pressure (IAP) elevation during capnoperitoneum can cause adverse cardiovascular and respiratory effects. This study aimed to determine if a sequentially increased IAP affects cardiovascular and respiratory variables in anesthetized dogs and evaluate the effects of the constant-rate infusion of dexmedetomidine (Dex) on cardiovascular and respiratory variables with increased IAP. Five dogs were anesthetized and instrumented, and a Veress needle was equipped to adjust the IAP using a carbon dioxide insufflator. Stabilization was conducted for 1 h, and physiological variables were measured at IAPs of 0, 5, 10, 15, and 20 mmHg and after desufflation. After the washout period, the dogs underwent similar procedures along with a constant-rate infusion of dexmedetomidine. The cardiovascular effects of increased IAP up to 20 mmHg were not significant in healthy beagle dogs and those administered with dexmedetomidine. When comparing the control and dexmedetomidine groups, the overall significant effects of dexmedetomidine were noted on heart rate, cardiac output, and systemic vascular resistance during the experiment. Respiratory effects were not observed during abdominal insufflation when compared between different IAPs and between the two groups. Overall, an increased IAP of up to 20 mmHg did not significantly affect cardiovascular and respiratory variables in both the control and dexmedetomidine groups. This study suggests that the administration of a dexmedetomidine infusion is applicable in laparoscopic procedures in healthy dogs.

Isomers of the Tomato Glycoalkaloids α-Tomatine and Dehydrotomatine: Relationship to Health Benefits.

High-performance liquid chromatography (HPLC) analysis of three commercial tomatine samples and another isolated from green tomatoes revealed the presence of two small peaks in addition to those associated with the glycoalkaloids dehydrotomatine and α-tomatine. The present study investigated the possible structures of the compounds associated with the two small peaks using HPLC-mass spectrophotometric (MS) methods. Although the two peaks elute much earlier on chromatographic columns than the elution times of the known tomato glycoalkaloids dehydrotomatine and α-tomatine, isolation of the two compounds by preparative chromatography and subsequent analysis by MS shows the two compounds have identical molecular weights, tetrasaccharide side chains, and MS and MS/MS fragmentation patterns to dehydrotomatine and α-tomatine. We suggest the two isolated compounds are isomeric forms of dehydrotomatine and α-tomatine. The analytical data indicate that widely used commercial tomatine preparations and those extracted from green tomatoes and tomato leaves consist of a mixture of α-tomatine, dehydrotomatine, an α-tomatine isomer, and a dehydrotomatine isomer in an approximate ratio of 81:15:4:1, respectively. The significance of the reported health benefits of tomatine and tomatidine is mentioned.

Mechanisms of the Device Property Alteration Generated by the Proton Irradiation in GaN-Based MIS-HEMTs Using Extremely Thin Gate Insulator.

Recently, we reported that device performance degradation mechanisms, which are generated by the γ-ray irradiation in GaN-based metal-insulator-semiconductor high electron mobility transistors (MIS-HEMTs), use extremely thin gate insulators. When the γ-ray was radiated, the total ionizing dose (TID) effects were generated and the device performance deteriorated. In this work, we investigated the device property alteration and its mechanisms, which were caused by the proton irradiation in GaN-based MIS-HEMTs for the 5 nm-thick Si3N4 and HfO2 gate insulator. The device property, such as threshold voltage, drain current, and transconductance varied by the proton irradiation. When the 5 nm-thick HfO2 layer was employed for the gate insulator, the threshold voltage shift was larger than that of the 5 nm-thick Si3N4 gate insulator, despite the HfO2 gate insulator exhibiting better radiation resistance compared to the Si3N4 gate insulator. On the other hand, the drain current and transconductance degradation were less for the 5 nm-thick HfO2 gate insulator. Unlike the γ-ray irradiation, our systematic research included pulse-mode stress measurements and carrier mobility extraction and revealed that the TID and displacement damage (DD) effects were simultaneously generated by the proton irradiation in GaN-based MIS-HEMTs. The degree of the device property alteration was determined by the competition or superposition of the TID and DD effects for the threshold voltage shift and drain current and transconductance deterioration, respectively. The device property alteration was diminished due to the reduction of the linear energy transfer with increasing irradiated proton energy. We also studied the frequency performance degradation that corresponded to the irradiated proton energy in GaN-based MIS-HEMTs using an extremely thin gate insulator.

Temporary Surgical Management of Intraventricular Hemorrhage in Premature Infants.

Post-hemorrhagic hydrocephalus (PHH) in preterm infant is common, life-threatening and the main cause of bad developmental outcomes. Ventriculoperitoneal (VP) shunt is used as the ultimate treatment for PHH. Low birth weight and low gestational age are the combination of worse prognostic factors while the single most important prognostic factor of VP shunting is age. Aggressive and early intervention have better effect in intraventricular hemorrhage and intracranial pressures control. It reduces infection rate and brain damage resulted in delayed shunt insertion. It is extremely important to let PHH infants get older and gain weight to have internal organs to be matured before undergoing VP shunt. As premature infants undergo shunt after further growth, shunt-related complications would be reduced. So temporary surgical intervention is critical for PHH infants to have them enough time until permanently shunted.

Effectiveness of C1 Laminectomy for Chiari Malformation Type 1: Posterior Fossa Volume Expansion and Syrinx-Volume Decrease Rate.

PURPOSE: This study aimed to analyze the effect of foramen magnum decompression with C1 laminectomy (C1L) for Chiari malformation type 1 (CM-1) in terms of improving clinical symptoms, expanding posterior fossa volume, and decreasing syrinx volume. MATERIALS AND METHODS: Between January 2007 and June 2019, 107 patients with CM-1 were included. The median patient age was 13±13 years (range: 9 months-60 years), female-to-male ratio was 1:1, and average length of tonsil herniation was 13±5 mm (range: 5-24 mm). Surgical techniques were divided into four groups based on duraplasty or C1L usage. Among the study subjects, 38 patients underwent duraplasty and had their syrinx volumes measured separately on serial magnetic resonance imaging. A three-dimensional visualization software was used to evaluate the syrinx-volume decrease rate. RESULTS: Bony decompression exhibited a mere 20% volume expansion of the lower-half posterior fossa. C1L offered a 3% additional volume expansion, which rose to 5% when duraplasty was added (p=0.029). There were no significant differences in complication rate when C1L was combined with duraplasty (p=0.526). Syrinx volumes were analyzed in 38 patients who had undergone duraplasty. Among them, 28 patients who had undergone duraplasty without C1L demonstrated a 5.9% monthly decrease in syrinx volume, which was 7.5% in the remaining 10 patients with C1L (p=0.040). CONCLUSION: C1L was effective in increasing posterior fossa volume expansion, both with and without duraplasty. A more rapid decrease in syrinx volume occurred when C1L was combined with duraplasty.

Ultra-Low Level Somatic Mutations and Structural Variations in Focal Cortical Dysplasia Type II.

OBJECTIVE: Brain somatic mutations in mTOR pathway genes are a major genetic etiology of focal cortical dysplasia type II (FCDII). Despite a greater ability to detect low-level somatic mutations in the brain by deep sequencing and analytics, about 40% of cases remain genetically unexplained. METHODS: We included 2 independent cohorts consisting of 21 patients with mutation-negative FCDII without apparent mutations on conventional deep sequencing of bulk brain. To find ultra-low level somatic variants or structural variants, we isolated cells exhibiting phosphorylation of the S6 ribosomal protein (p-S6) in frozen brain tissues using fluorescence-activated cell sorting (FACS). We then performed deep whole-genome sequencing (WGS; >90×) in p-S6+ cells in a cohort of 11 patients with mutation-negative. Then, we simplified the method to whole-genome amplification and target gene sequencing of p-S6+ cells in independent cohort of 10 patients with mutation-negative followed by low-read depth WGS (10×). RESULTS: We found that 28.6% (6 of 21) of mutation-negative FCDII carries ultra-low level somatic mutations (less than 0.2% of variant allele frequency [VAF]) in mTOR pathway genes. Our method showed ~34 times increase of the average mutational burden in FACS mediated enrichment of p-S6+ cells (average VAF = 5.84%) than in bulky brain tissues (average VAF = 0.17%). We found that 19% (4 of 21) carried germline structural variations in GATOR1 complex undetectable in whole exome or targeted gene sequencing. CONCLUSIONS: Our method facilitates the detection of ultra-low level somatic mutations, in specifically p-S6+ cells, and germline structural variations and increases the genetic diagnostic rate up to ~80% for the entire FCDII cohort. ANN NEUROL 2023;93:1082-1093.

Systematic evaluation of genome-wide metabolic landscapes in lactic acid bacteria reveals diet- and strain-specific probiotic idiosyncrasies.

Lactic acid bacteria (LAB) are well known to elicit health benefits in humans, but their functional metabolic landscapes remain unexplored. Here, we analyze differences in growth, intestinal persistence, and postbiotic biosynthesis of six representative LAB and their interactions with 15 gut bacteria under 11 dietary regimes by combining multi-omics and in silico modeling. We confirmed predictions on short-term persistence of LAB and their interactions with commensals using cecal microbiome abundance and spent-medium experiments. Our analyses indicate that probiotic attributes are both diet and species specific and cannot be solely explained using genomics. For example, although both Lacticaseibacillus casei and Lactiplantibacillus plantarum encode similarly sized genomes with diverse capabilities, L. casei exhibits a more desirable phenotype. In addition, "high-fat/low-carb" diets more likely lead to detrimental outcomes for most LAB. Collectively, our results highlight that probiotics are not "one size fits all" health supplements and lay the foundation for personalized probiotic design.

Effect of Fermented Sarco Oyster (Crassostrea gigas) Extract on Muscle Strength Enhancement in Postmenopausal Females: A Randomized, Double-Blind, Placebo-Controlled Trial.

A randomized controlled trial (RCT) was conducted to evaluate the effect of fermented sarco oysters (FSO) on muscle strength in postmenopausal females with low muscle mass. Fifty-two female participants were randomly divided into the experiment group (EG) or control group (CG). For 12 weeks, the EG was subjected to 1000 mg of FSO extract daily while the CG consumed the placebo extract. The muscle extension and flexion at an angular velocity of 60°/s and with respect to grip strength, body composition, and muscle growth-related blood factors were measured at the baseline and after the trial. The difference in the quadriceps muscle extension at an angular velocity of 60°/s, grip strength on both the left and right side, and insulin-like growth factor-1(IGF-1) between groups were significantly higher in the EG compared with the CG. However, no differences were found in body composition, blood pyruvate, lactate, or high-sensitivity C-reactive protein (hsCRP) concentration between the two groups. In conclusion, FSO supplements may improve muscle strength in postmenopausal females with relatively reduced muscle strength without a change in muscle mass.

Comparison of sitting and prone positions for real-time ultrasound-guided thoracic epidural catheter placement: a randomized controlled trial.

INTRODUCTION: Real-time ultrasound-guided thoracic epidural catheter placement (US-TECP) has been recently introduced. Patient's position is associated with the success of spine interventions; however, the effects of position on the outcome of the procedure remain unknown. We aimed to assess the clinical usefulness of patient positioning during real-time US-TECP. METHODS: Patients were randomly assigned to the prone position group (group P) and sitting position group (group S). The primary outcome was needling time during the procedure. The secondary outcomes were time to mark space, total number of needle passes, number of skin punctures, first-pass success, final success, crossover success, and visibility of ultrasound (US) views. Global Rating Scale (GRS) score, Patient Comfort Scale score, procedural pain intensity, patient satisfaction, and procedure-related complications were also determined. RESULTS: Sixty-four patients were included in this study. The needling time was significantly shorter in group P than in group S (36.5 (26.5-51.0) vs 59.5 (34.5-152.0) s, p<0.01). The numbers of needle passes and skin punctures were significantly lesser in group P than in group S. First-pass success was higher in group P than in group S. Group P had higher GRS compared with group S. The time to mark space, final success, US visibility score, Patient Comfort Scale score, procedural pain intensity, and patient satisfaction did not differ between the groups. One patient in group S developed a vasovagal reaction. DISCUSSION: This study shows that prone position may be preferred for real-time US-TECP, considering its better clinical usefulness. TRIAL REGISTRATION NUMBER: KCT0005757.

Clinical features and management of snake bites in 70 dogs in Korea.

BACKGROUND: Snakebites remain a devastating and life-threatening environmental hazard. While the management of snakebites has been well described in humans, few clinical data and guidelines exist for dogs, especially in Korea. OBJECTIVES: This retrospective study evaluated the clinical features of 70 dogs with snakebite wounds in Korea. METHODS: The medical records of 72 dogs that presented to three animal hospitals from June 2008 to July 2021 were reviewed; among these, 70 dogs that met the inclusion criteria were enrolled. Their signalment, history, clinical signs, physical examination, blood analysis, treatment, and prognosis were also evaluated. RESULTS: Of 70 dog owners, 35 (50%) witnessed the bite, with a mean time between bite and hospital presentation of 9.7 ± 4.1 h in 58 dogs. Blood smears were evaluated in 45 dogs, of which 28 (62%) showed echinocytosis. Anemia and acute kidney injury were found in 21 (29%) and 2 dogs (3%), respectively. A total of 37 dogs (53%) were hospitalized, 5 (7%) of which died. CONCLUSIONS: The most significant finding was the high prevalence of echinocytosis. The data from this retrospective study could inform the management of dogs bitten by snakes in Korea.

Factors Associated With Rebound Pain After Patient-controlled Epidural Analgesia in Patients Undergoing Major Abdominal Surgery: A Retrospective Study.

OBJECTIVES: Although patient-controlled epidural analgesia (PCEA) is an effective form of regional analgesia for abdominal surgery, some patients experience significant rebound pain after the discontinuation of PCEA. However, risk factors for rebound pain associated with PCEA in major abdominal surgery remain unknown. This study evaluated the incidence of rebound pain related to PCEA and explored potential associated risk factors. MATERIALS AND METHODS: We performed a retrospective review of 236 patients using PCEA following hepatobiliary and pancreas surgery between 2018 and 2020 in a tertiary hospital in South Korea. Rebound pain was defined as an increase from well-controlled pain (numeric rating scale <4) during epidural analgesia to severe pain (numeric rating scale ≥7) within 24 hours of discontinuation of PCEA. Logistic regression analysis was performed to determine the factors associated with rebound pain. RESULTS: Patients were categorized into the nonrebound pain group (170 patients; 72%) and the rebound pain group (66 patients; 28%). Multivariable logistic regression analysis revealed that preoperative prognostic nutritional index below 45 (odds ratio=2.080, 95% confidential interval=1.061-4.079, P =0.033) and intraoperative transfusion (odds ratio=4.190, 95% confidential interval=1.436-12.226, P =0.009) were independently associated with rebound pain after PCEA discontinuation. DISCUSSION: Rebound pain after PCEA occurred in ~30% of patients who underwent major abdominal surgery, resulting in insufficient postoperative pain management. Preoperative low prognostic nutritional index and intraoperative transfusion may be associated with rebound pain after PCEA discontinuation.

Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Development of a machine learning model for the prediction of the short-term mortality in patients in the intensive care unit.

PURPOSE: The aim of this study was to develop and evaluate a machine learning model that predicts short-term mortality in the intensive care unit using the trends of four easy-to-collect vital signs. MATERIALS AND METHODS: The primary training cohort included 1968 patients at the Veterans Health Service Medical Center. The external validation cohort comprised 409 patients at Seoul National University Hospital. Datasets of heart rate, systolic blood pressure, diastolic blood pressure, and peripheral capillary oxygen saturation (SpO2) measured every hour for 10 h were used. The performances of mortality prediction models generated using five machine learning algorithms, Random Forest (RF), XGboost, perceptron, convolutional neural network, and Long Short-Term Memory, were calculated and compared using area under the receiver operating characteristic curve (AUROC) values and an external validation dataset. RESULTS: The machine learning model generated using the RF algorithm showed the best performance. Its AUROC was 0.922, which is much better than the 0.8408 of the Acute Physiology and Chronic Health Evaluation II. The machine learning model developed using SpO2 showed the best performance (AUROC, 0.89). CONCLUSIONS: This simple yet powerful new mortality prediction model could be useful for early detection of probable mortality and appropriate medical intervention, especially in rapidly deteriorating patients.

LGI3 promotes human keratinocyte migration in high-glucose environments by increasing the expression of ß-catenin.

The leucine-rich repeat LGI family member 3 (LGI3) has been reported to regulate various functions in epidermal keratinocytes. In this study, we investigated the effects of LGI3 on keratinocyte migration in environments with different glucose concentrations. Our results showed that cell migration is markedly impaired in high-glucose environments compared to in low-glucose environments (control). Nevertheless, the use of LGI3 in high-glucose environments restores cell migration to the normal level. Therefore, we performed LGI3 knockdown to identify the role of LGI3 in cell migration. It was observed that transfecting LGI3 siRNA into HaCaT cells reduces the expression of LGI3 and inhibits wound closure. These results indicate that LGI3 is deeply involved in wound healing in high-glucose environments. Western blot analysis showed that in high-glucose environments, LGI3 increases the phosphorylation of Akt, forkhead box protein O1, and focal adhesion kinase. However, no change was observed in the levels of glycogen synthase kinase 3ß, c-Jun N-terminal kinase, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. Further results showed that LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, reduced LGI3-induced cell migration. It is generally known that Akt activation leads to the accumulation of ß-catenin, an important mediator of keratinocyte migration. LGI3 greatly increased the expression of ß-catenin in high-glucose environments comparison to that in the low-glucose environments. Taken together, these data indicate that LGI3 induces keratinocyte migration in high-glucose environments as a result of ß-catenin accumulation via Akt phosphorylation. Therefore, LGI3 can be considered a new treatment option for diabetic wound healing.