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Recent advances in two-dimensional (2D) crystals make it possible to realize an ideal interface structure that is required for device applications. Specifically, a p-n junction made of 2D crystals is predicted to exhibit an atomically well-defined interface that will lead to high device performance. Using angle-resolved photoemission spectroscopy, a simple surface treatment was shown to allow the possible formation of such an interface. Ta adsorption on the surface of a p-doped SnSe shifts the valence band maximum towards the higher binding energy due to the charge transfer from Ta to SnSe that is highly localized at the surface due to the layered structure of SnSe. As a result, the charge carriers of the surface are changed from holes of its bulk characteristics to electrons, while the bulk remains as a p-type semiconductor. This observation suggests that the well-defined interface of a p-n junction with an atomically thin n-region is formed between Ta-adsorbed surface and bulk.

Objective: To describe the sonographic findings for malignant mixed Müllerian tumors (MMMTs) of the uterus with particular emphasis on their features on saline contrast sonohysterography (SCSH) and color Doppler sonography, and to determine how they relate to pathological findings. Methods: The SCSH and color Doppler findings in 29 histologically proven cases of uterine MMMT were reviewed retrospectively and their relationship to gross and histological findings were investigated. Results: Of the 29 uterine tumors, 16 were located only in the corpus, nine only in the fundus and four in both the corpus and fundus. Mean tumor size was 5.4 cm. The most common appearance was a polypoid mass projecting into the endometrial cavity, found in 23 cases. Twenty-eight tumors had an irregular surface, which was papillary in 20 cases and lobulated in eight. Most appeared heterogeneously isoechoic (n = 16) or hypoechoic (n = 12), occasionally with a trabecular appearance, and they often had clefts or fissure-like cystic areas (n = 10), necrosis (n = 4) or hemorrhagic areas (n = 7). Myometrial invasion was present in 27 cases and dilatation of the endometrial cavity was seen in 11. Color Doppler sonography showed moderate to marked vascularity in 20 out of the 24 cases in which it was performed, with a mean resistance index of 0.41, and appeared as feeding (n = 15) or randomly dispersed (n = 9) vessels. Conclusions: Uterine MMMTs have distinct sonographic features that are related to pathological findings. Knowledge of the sonographic appearance of MMMTs may facilitate diagnosis. [ABSTRACT FROM AUTHOR]

This study was designed to determine the accuracy and agreement of a self-collection method using pad for human papillomavirus (HPV) DNA. One hundred and thirty-four patients at university hospitals voluntarily participated in the accuracy study, and 314 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers designed for the direct sequencing. In the accuracy study, all samples were probed via histological examinations. With regard to the detection of squamous intraepithelial lesion (SIL), self-collection pad sampling displays sensitivity, of 76.9%, and specificity, of 93.3%. Three hundred and fourteen self-collection pad samples and the concurrent physicians' samples showed a 97.8% agreement, with a Kappa value of 0.9200. A new self-collection pad for the detection of HPV DNA appears to constitute an easy, rapid, and convenient alternative method for the cervical cancer screening of many women with the virtue of being incredibly readily accessible. [ABSTRACT FROM AUTHOR]

Introduction: Bisphosphonates are effective for treating osteoporosis, Paget's disease of bone, and malignancy-associated bone diseases. Bisphosphonate-associated osteonecrosis of the jaw (ONJ) is a rare but serious adverse effect of bisphosphonate therapy. Due to inhibitory actions on bone turnover, bisphosphonate therapy may result in the accumulation of microdamage.Case summary: A 74-year-old Korean woman (height, 150 cm; weight, 51 kg) was referred to the Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea, for evaluation of pain and persistent abnormal exposure of jaw bone after extraction of teeth. She had been receiving weekly oral alendronate treatment for osteoporosis for approximately 5 years. The patient had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by teeth extraction approximately 14 months prior to the outpatient referral visit. At her clinical baseline visit, serum hormone concentrations and bone turnover markers were as follows: thyroid-stimulating hormone, 0.88 ?IU/mL (reference range, 0.25-5.00 ?IU/mL); 25-hydroxyvitamin D[3], 20.9 (9.0-37.6) ng/mL; parathyroid hormone (PTH), 57 (11-62) pg/mL; serum osteocalcin, 8.7 (12.9-55.9) ng/mL; and urine N-telopeptide 21 (26-124) nM/mM creatinine. She had multiple systemic risk factors for ONJ, including older age, type 2 diabetes mellitus, and long duration of bisphosphonate therapy. There was no mandibular lesion improvement despite repeated surgical procedures performed within a 14-month period. Bisphosphonate therapy was discontinued and PTH therapy was started. After 2 months, exposed oral mucosa had healed. After 4 months of treatment, the pain had completely subsided, and after 6 months the patient's eating and drinking habits returned. The serum concentration of osteocalcin, a bone formation marker, which was initially suppressed (8.7 ng/mL), increased 174% (15.1 ng/mL) from baseline after 6 months of treatment with PTH.Conclusions: Here we report a probable case of oral bisphosphonate-associated ONJ featuring suppressed bone turnover. Treatment with the bone formation-stimulating agent PTH was beneficial. [ABSTRACT FROM AUTHOR]

Controlling the microenvironment surrounding the pluripotent stem cells (PSCs) is a pivotal strategy for regulating cellular differentiation. Surface nanotopography is one of the key factors influencing the lineage-specific differentiation of PSCs. However, much of the underlying mechanism remains unknown. In this study, we focused on the effects of gradient nanotopography on the differentiation of embryoid bodies (EBs). EBs were cultured on three differently sized nanopillar surfaces (Large, 280-360; Medium, 200-280; Small, 120-200 nm) for spontaneous cardiomyocyte differentiation without chemical stimuli. The large nanotopography significantly promoted cardiogenesis, with increased expression of cardiac markers such as α-MHC, cTnT, and cTnI, and redistributed vinculin expression to the contact area. In addition, the small and medium nanotopographies also influenced EB differentiation, affecting both cardiogenesis and hematopoiesis to varying degrees. The phosphorylation of focal adhesion kinase (FAK) decreased in the EBs on the large nanotopography compared to that in the EBs cultured on the flat surface. The gradient nanotopography with 280-360 nm nanopillars is beneficial for the cardiogenesis of EBs in a FAK-dependent manner. This study provides valuable insights into controlling stem cell differentiation through nanotopographical cues, thereby advancing our understanding of the microenvironmental regulation in stem cell-based cardiac tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

SARS-CoV-2 mutations have resulted in the emergence of multiple concerning variants, with Omicron being the dominant strain presently. Therefore, we developed a monoclonal antibody (mAb) against the spike (S) protein of SARS-CoV-2 Omicron for therapeutic applications. We established the 1E3H12 mAb, recognizing the receptor binding domain (RBD) of the Omicron S protein, and found that the 1E3H12 mAb can efficiently recognize the Omicron S protein with weak affinity to the Alpha, Beta, and Mu variants, but not to the parental strain and Delta variant. Based on in vitro assays, the mAb demonstrated neutralizing activity against Omicron BA.1, BA.4/5, BQ.1.1, and XBB. A humanized antibody was further produced and proved to have neutralizing activity. To verify the potential limitations of the 1E3H12 mAb due to viral escape of SARS-CoV-2 Omicron variants, we analyzed the emergence of variants by whole genome deep sequencing after serial passage in cell culture. The results showed a few unique S protein mutations in the genome associated with resistance to the mAb. These findings suggest that this antibody not only contributes to the therapeutic arsenal against COVID-19 but also addresses the ongoing challenge of antibody resistance among the evolving subvariants of SARS-CoV-2 Omicron., (Copyright © 2024. Published by Elsevier Masson SAS.)

Several recent studies have presented evidence that the human gene catalogue should be expanded to include thousands of short open reading frames (ORFs) appearing upstream or downstream of existing protein-coding genes, each of which might create an additional bicistronic transcript in humans. Here we explore an alternative hypothesis that would explain the translational and evolutionary evidence for these upstream ORFs without the need to create novel genes or bicistronic transcripts. We examined 2,199 upstream ORFs that have been proposed as high-quality candidates for novel genes, to determine if they could instead represent protein-coding exons that can be added to existing genes. We checked for the conservation of these ORFs in four recently sequenced, high-quality human genomes, and found a large majority (87.8%) to be conserved in all four as expected. We then looked for splicing evidence that would connect each upstream ORF to the downstream protein-coding gene at the same locus, thus creating a novel splicing variant using the upstream ORF as its first exon. These protein coding exon candidates were further evaluated using protein structure predictions of the protein sequences that included the proposed new exons. We determined that 541 out of 2,199 upstream ORFs have strong evidence that they can form protein coding exons that are part of an existing gene, and that the resulting protein is predicted to have similar or better structural quality than the currently annotated isoform., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2024 Ji, Salzberg. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, the ultraviolet B (UVB)-induced skin photoaging inhibitory activity of pomegranate peel extract with increased ellagic acid content through enzymatic hydrolysis was evaluated in HaCaT cells. Among various enzymes, Viscozyme with high tannase and β-glucosidase activities was used, and 1.0 % Viscozyme was added to hydrolyze pomegranate peel for 2 h at 40°C to establish the optimal reaction conditions for high ellagic acid content. Subsequently, when cells were treated with enzyme extracted pomegranate peels (40 μg/mL), the gene expression of matrix metalloproteinases (MMP)-2 and 13, which play key role in skin elasticity and moisture, and the protein expression of MMP13 were downregulated compared to the UVB-control group (UVB-C). In addition, the protein expression levels of tissue inhibitors, metalloproteinase-1 and 2, and collagen type I alpha 1 were upregulated, the gene expression of hyaluronic acid synthase-1, and filaggrin significantly increased, and interleukin-1β increased by photoaging was decreased. Furthermore, compared to the UVB-C, there was a significant increase in the gene expression of superoxide dismutase-1 and glutathione peroxidase, which resulted in a decrease in reactive oxygen species and malondialdehyde levels. These results were confirmed to be due to the inhibition of the mitogen-activated protein kinase pathway and downregulation of the protein expression of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38. In conclusion, pomegranate peel, from which ellagic acid was extracted using Viscozyme, showed a reactive oxygen species inhibitory effect in UVB-irradiated HaCaT cells and thus may have a significant potential as a cosmetic ingredient with anti-aging effects., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hyung Joo Suh reports financial support was provided by Korea Ministry of Small and Medium Enterprises and Startups. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

This study compared the antihypertensive effects of avenanthramides A, B, and C, with a focus on their antioxidant and anti-inflammatory properties. Treatment with avenanthramides A, B, and C (50 μM) significantly enhanced cell viability and nitric oxide production in H2O2-induced endothelial dysfunction in EA.hy926 cells. Avenanthramides notably increased the levels of antioxidant enzymes and glutathione while reducing malondialdehyde and reactive oxygen species. Moreover, avenanthramides promoted the Nrf2 translocation to nucleus, enhancing the expression of antioxidant enzymes. Furthermore, avenanthramides inhibited the protein levels of iNOS and COX-2, as well as the phosphorylation of IkBα and translocation of p65, thereby mitigating endothelial inflammation. Molecular docking analysis revealed that avenanthramide A exhibited the strongest binding affinity for HO-1 and iNOS, which was correlated with its superior biological activity. Overall, by upregulating Nrf2/HO-1 pathways and downregulating NF-kB pathways, avenanthramides show potential as therapeutic agents for the treatment of endothelial dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: This study aimed to compare long-term clinical outcomes of percutaneous needle biopsy (PCNB) versus surgical biopsy in patients with peripheral, small-sized clinical stage 1 non-small cell lung cancer (NSCLC) with computed tomography (CT)-defined visceral pleural invasion (VPI)., Methods: We retrospectively analyzed patients who underwent surgery for NSCLC with CT-defined VPI between 2010 and 2017. We excluded patients with non-peripheral NSCLC, or cancers > 3 cm. Propensity score matching was carried out to adjust for confounding variables. The primary endpoint was ipsilateral pleural recurrence-free survival, while secondary endpoints included overall survival and recurrence-free survival., Results: Of the 1671 patients with peripheral, small-sized clinical stage 1 NSCLC with CT-defined VPI, 805 underwent PCNB, and 866 had a surgical biopsy. Propensity score matching assigned 562 patients to each group. Before matching, the PCNB group demonstrated worse baseline characteristics, including older age, higher smoking history, and more adverse pathological findings. After matching, the 5-year recurrence-free survival for ipsilateral pleural recurrence (98.6% vs. 96.0%, p = 0.002) and overall survival (93.8% vs. 90.2%, p = 0.003) were significantly higher in the surgical biopsy group compared with the PCNB group. Multivariable analysis revealed that PCNB significantly increased the risks of all-cause mortality and various recurrences before and after matching., Conclusions: Compared with surgery biopsy, PCNB was associated with higher risks of all-cause mortality and recurrences, including ipsilateral pleural recurrence. PCNB should be considered with caution in cases of peripheral stage 1 NSCLC where CT-defined VPI is suspected., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The Geostationary Environment Monitoring Spectrometer (GEMS) is the world's first geostationary instrument that monitors hourly gaseous air pollutant levels, including nitrogen dioxide (NO 2 ). Using the first-of-its-kind capabilities of GEMS NO 2 data, we examined how well GEMS NO 2 levels can explain the spatiotemporal variabilities in hourly NO 2 concentrations in the Republic of Korea for the year 2022. A correlation analysis between hourly GEMS NO 2 levels and ground NO 2 concentrations showed a higher spatial correlation [Pearson r = 0.56 (SD = 0.20)] than a temporal one [Pearson r = 0.42 (SD = 0.14)], on average. To take advantage of the enhanced spatial predictability of GEMS NO 2 data, we employed a mixed effects model to allow hour-specific relationships between GEMS NO 2 and NO 2 concentrations on a given day in each region and subsequently estimated hourly NO 2 concentrations in all urban and rural areas. The 10-fold cross validation demonstrated R 2  = 0.72, mean absolute error (MAE) = 3.7 ppb, and root mean squared error (RMSE) = 5.5 ppb. The hourly variations of the relationships were attributed particularly to those of wind speed among meteorological parameters considered in this study. The spatial distributions of hourly estimated NO 2 concentrations were highly correlated between hours [average r = 0.91 (SD = 0.06)]. Nonetheless, they represented the diurnal patterns of urban versus rural NO 2 contrasts during the day [urban/rural NO 2 ratios from 1.22 (5 p.m.) to 1.37 (12 p.m.)]. The newly retrieved GEMS NO 2 data enable temporally as well as spatially resolved NO 2 exposure assessment. In combination with the time-activity patterns of individual subjects, the GEMS NO 2 data can generate 'sub-population' exposure estimates and therefore enhance health effect studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies reported that short-term exposure to ground-level ozone is associated with mortality risk. However, due to the limited monitored areas, existing studies were limited in assessing the nationwide risk and suggesting specific vulnerable populations to the ozone-mortality risk., Methods: We performed a nationwide time-stratified case-crossover study to evaluate the association between short-term ozone and cause-specific mortality in South Korea (2015-2019). A machine learning-ensemble prediction model (a test R 2  > 0.96) was used to assess the short-term ozone exposure. Stratification analysis was conducted to examine the high-risk populations, and the excess mortality due to non-compliance with the WHO guideline was also assessed., Results: For all-cause mortality (1,343,077 cases), the risk associated with ozone (lag0- 1) was weakly identified (odd ratio: 1.005 with 95% CI: 0.997-1.014), and the risk was prominent in mortality with circulatory system diseases. In addition, based on the point estimates, the ozone-mortality risk was higher in people aged less than 65y, and this pattern was also observed in circulatory system disease deaths and urban areas., Conclusions: This study provides national estimates of mortality risks associated with short-term ozone. Results showed that the benefits of stricter air quality standards could be greater in vulnerable populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Over the past two decades, ambient O 3 air pollution in Seoul, the capital city of South Korea, has increased. As a secondary air pollutant, O 3 is affected not only by precursor gas emissions but also by meteorological conditions. This study examined the influence of weather changes in Seoul for 2001-2019 on the long-term daily maximum 8-h O 3 concentration (MDA8 O 3 ) trends measured at 25 monitoring sites. As the relationship between O 3 and meteorological variables may not be linear, we used a generalized additive model framework to estimate O 3 trends, incorporating quantile and logistic regressions for continuous O 3 data and O 3 exceedance days (>60 ppb), respectively. Over the 19-year period, the O 3 concentrations in Seoul increased by 14.7 (SD = 3.2) and 13.1 (SD = 3.1) ppb before and after adjusting for local meteorology, respectively, resulting in an average weather penalty of 1.55 ppb. Seasonal variations in the penalty were substantial, showing a greater penalty (4.5 ppb) during the warm season (May-October) than during the cold season (November-April). Furthermore, the increase in O 3 concentration was more pronounced on days with comparatively high O 3 levels. During the warm season, the weather penalties on O 3 trends reached 3.7-4.0 ppb on high-O 3 days (75 th , 95 th , and 99 th percentiles). From 2001 to 2019, the O 3 exceedance days started 2.66 days earlier and ended 2.30 days later per year, extending the peak-O 3 season by approximately 89 days in total. Weather changes accelerated the upward trend in the odds ratio of O 3 exceedance days by 3.8 years. Our findings indicate that O 3 exceedance days can occur in nearly all months owing to weather changes. The significant weather penalties on O 3 concentrations and exceedance days emphasize the need for a comprehensive O 3 air pollution mitigation strategy, considering non-emission factors that are increasingly being recognized in the context of climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 77-year-old professional gold craftsman ingested a white powder used in goldsmithing, mistaking the powder for a health supplement. He detected a strange taste and immediately fell sick, reported the incident to 911, and was taken to the emergency room. He died approximately 8.5 h post-ingestion despite treatment. There were no significant findings in the autopsy, the victim's heart blood sample, gastric contents, and the white powder the victim had taken were submitted to the department of forensic toxicology. Using scanning electron microscopy energy dispersive X-ray analysis, potassium and gold (Au) were detected in the white powder. Ion chromatography analysis detected cyanide. Concentrations of cyanide were 0.5 mg/L in heart blood and 13.3 mg/L in gastric contents. Qualitative and quantitative analyses of Au in the heart blood sample and gastric contents using inductively coupled plasma-optical emission spectrometry detected concentrations of 79.8 mg/L and 2010.1 mg/L, respectively. Au and cyanide synergistically enhance cytotoxicity through inhibition of detoxification and increasing intracellular accumulation. In the present case, the detected blood cyanide concentration was sub or minimally lethal, and the blood Au concentration was high. The cause of the victim's death was the combined toxicity of Au and cyanide., (© 2024 American Academy of Forensic Sciences.)

To evaluate the real-world impact of artificial intelligence (AI) on radiologists' reading time during bone age (BA) radiograph assessments. Patients (<19 year-old) who underwent left-hand BA radiographs between December 2021 and October 2023 were retrospectively included. A commercial AI software was installed from October 2022. Radiologists' reading times, automatically recorded in the PACS log, were compared between the AI-unaided and AI-aided periods using linear regression tests and factors affecting reading time were identified. A total of 3643 radiographs (M:F=1295:2348, mean age 9.12 ± 2.31 years) were included and read by three radiologists, with 2937 radiographs (80.6%) in the AI-aided period. Overall reading times were significantly shorter in the AI-aided period compared to the AI-unaided period (mean 17.2 ± 12.9 seconds vs. mean 22.3 ± 14.7 seconds, p < 0.001). Staff reading times significantly decreased in the AI-aided period (mean 15.9 ± 11.4 seconds vs. mean 19.9 ± 13.4 seconds, p < 0.001), while resident reading times increased (mean 38.3 ± 16.4 seconds vs. 33.6 ± 15.3 seconds, p = 0.013). The use of AI and years of experience in radiology were significant factors affecting reading time (all, p≤0.001). The degree of decrease in reading time as experience increased was larger when utilizing AI (-1.151 for AI-unaided, -1.866 for AI-aided, difference =-0.715, p<0.001). In terms of AI exposure time, the staff's reading time decreased by 0.62 seconds per month (standard error 0.07, p<0.001) during the AI-aided period. The reading time of radiologists for BA assessment was influenced by AI. The time-saving effect of utilizing AI became more pronounced as the radiologists' experience and AI exposure time increased., Competing Interests: Declarations Ethics Approval This retrospective study was approved by the Institutional Review Board of our institution. Informed consent was waived due to its retrospective nature. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and regulations. Competing Interests There is no conflict of interest to declare., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Diabetes mellitus (DM) is a multifaceted metabolic condition, mainly defined by elevated blood glucose levels. A feature of type 2 DM includes insulin resistance (IR), which involves impairments within the insulin signaling pathways. Avenanthramides (AVNs) are phenolic alkaloids found in Avena sativa L. The major AVNs are AVN A, AVN B, and AVN C. They have been reported to offer benefits in preventing inflammation, cancer, and cardiovascular diseases. However, the effects of AVNs on the liver glucose metabolism pathways remain unknown. This study examined the effects and underlying mechanisms through which AVNs alleviate IR induced by free fatty acid (FFA) in HepG2 cells. The results indicated that FFA treatment significantly decreased glucose consumption by 34.54% compared to the control. However, treatments with AVN A, B, and C at 100 μM increased glucose uptake by 57.93%, 58.28%, and 53.10%, respectively, compared to FFA treatment alone. This effect occurs through the increased expression of glucose transporter 4. Furthermore, AVNs significantly enhanced the glycogen content. AVNs induced increased phosphorylation of insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). AVNs treatment decreased the levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in HepG2 cells. This effect was attributed to AMP-activated protein kinase activation and inhibition of forkhead box protein O1. Collectively, these results suggest that AVNs regulate glucose metabolism by activating the IRS-1/PI3K/Akt pathway, which is related to glycogen synthesis, and by inhibiting key molecules that promote gluconeogenesis.

We propose a sensor event-driven, open-column chromatographic sample preparation system─OpenPrep. This system replaces the problematic flow selector valve with a noncontact built-in sensor, eliminating carryover and clogging issues, which are commonly encountered in pump-driven chromatographic systems. The innovative valveless column-flow design, combined with a compact gantry dispenser and motion stage-based fraction collector, reduces the sample flow path to a disposable component with a postcolumn dead volume of only 0.5 mL. This configuration is superior to conventional dynamic flow systems owing to its ability to minimize sample consumption, eluent loss, and cleaning waste generation. Thus, OpenPrep can be ideal for preventing cross-contamination. Owing to the rapid flow-transfer and stop approach, OpenPrep achieves higher reagent delivery accuracy and precision compared to ISO 8655-2 piston-operated pipettes, by minimizing liquid residue on the dispensing tip. Sensor-driven flow control ensures precise eluent collection and automatic regulation of the mobile-phase flow rate through an online calibration algorithm, meeting all the requirements for accurate and reproducible column flow control. OpenPrep features an open architecture for both hardware and software, offering high flexibility for analyzing samples with considerable variations in radioactivity and matrix compositions, such as radioactive waste. The proof-of-concept implementation of a multistage sequential separation strategy, using five resin columns to separate Re, Sr, Fe, and Ni from a single sample, demonstrates that OpenPrep provides enhanced flexibility and reconfigurability, improved operational efficiency, and cost-effective customization. Excellent chemical yields were obtained for Re, Sr, and Ni in the range of 83-97%, with less than 2.6% relative standard deviation at a flow rate three times faster than the gravity method. Additionally, improved recovery performance of Fe was achieved by applying a slower flow rate compared to gravity flow.

Harrold et al. evaluate the fertility impact of checkpoint inhibitor blockade (ICB), demonstrating that unlike in utero exposure, post-exposure conception appears to result in uncomplicated pregnancies and healthy progeny. They demonstrate contemporaneous monitoring of temporal female hormonal fluctuations before, on, and post ICB exposure and prior to successful embryo implantation., Competing Interests: Declaration of interests E.H. has received funding from the Conquer Cancer ASCO Foundation. She has served as a consultant to Pfizer Ireland on one occasion in 2021 and to Takeda on one occasion in 2024. She reports educational grants from Merck and Amgen to attend GI ASCO 2020. M.P. has received personal fees for consulting from BMS, Merck, Novartis, Eisai, Pfizer, Chugai, Erasca, and Nektar. He reports institutional support from the following companies: RGenix, Infinity, BMS, Merck, Novartis, BioAtla, and Genentech. A.C. has served on advisory boards for the following companies: Abbvie, Amgen, Agenus, Daiichi Saynko, Janssen, GSK, Merck, Pfizer/Seagen Regeneron, and Roche. She has research funding from GSK and Pfizer/Seagen. She holds a pending patent for Neoadjuvant PD1 blockade in locally advanced mismatch repair deficient solid tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The bitter resins in hops (Humulus lupulus) modulate GABA receptors, leading to central nervous system suppression, which induces sedative effects and enhances sleep., Aim of the Study: This study intends to explore the sleep-enhancing properties of Hongcheon-hop extract, a hop native to Korea, by analyzing sleep structure and its mechanisms through EEG., Materials and Methods: A pentobarbital-induced sleep model was used, along with EEG analysis to study sleep architecture. The receptor binding of Hongcheon-hop extract was analyzed using GABA receptor antagonists., Results: The extract contained 7.44 mg/g of xanthohumol, 133.04 mg/g of α-acids including 13.74 mg/g of humulone and 84.52 mg/g of β-acids. Administration of the extracts resulted in a dose-dependent enhancement of sleep duration. Both low (100 mg/kg) and high doses (200 mg/kg) of the extract increased non-rapid eye movement (NREM) sleep by enhancing δ wave sleep, which represents deep sleep. The extract exerted its sleep-promoting effects by binding to the γ-aminobutyric acid (GABA) binding site on GABA A receptor. In an insomnia model, low dose of the extract was more effective than the same dose of GABA in enhancing sleep. Administration of the extract for 3 weeks increased the expression and protein levels of 5-HT 1A receptors in addition to GABA A receptor, and also increased the content of GABA in the brain. A mixture of xanthohumol (1.49 mg) and humulone (2.75 mg) within Hongcheon-hop extract (200 mg) exhibited a sleep-enhancing effect comparable to that of the extract., Conclusion: These findings suggest that Hongcheon-hop extract, which contains xanthohumol and humulone, improves sleep quality by increasing NREM sleep through the enhancement of δ-wave sleep via GABA A receptors. Hongcheon-hop shows potential as a natural therapeutic agent for treating insomnia and enhancing sleep., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Resting heart rate variability (HRV) is typically higher in those with better emotional well-being. In the current study, we examined whether changes in resting HRV mediated changes in negative emotions during a 7-week clinical trial of HRV biofeedback. Younger and older adults were randomly assigned to one of two daily biofeedback practices for 5 weeks: (1) engage in slow-paced breathing to increase the amplitude of oscillations in heart rate at their breathing frequency (Osc+); or (2) engage in self-selected strategies to decrease heart rate oscillations (Osc-). We assessed negative emotion using the State Anxiety Inventory (SAI) and Profile of Mood States (POMS). Resting HRV at pre-intervention was significantly higher among those with lower negative emotion scores. Those participants showing greater increases in resting HRV showed greater decreases in negative emotion. In a mediation model with all participants, resting HRV changes significantly mediated the relationship between training performance (i.e., heart rate oscillation during practice sessions) and changes in negative emotion. However, additional analyses revealed this mediation effect was significantly moderated by condition and was only significant in the Osc+ condition. Thus, resting HRV changes mediated how biofeedback to increase amplitude of heart rate oscillations reduced negative emotion., (© 2024. The Author(s).)

Objective: Patients with traumatic brain injury (TBI) commonly exhibit a poor mental health status and can easily develop aspiration pneumonia. Thus, early proper nutrition through oral or tube feeding is difficult to achieve, leading to malnutrition. However, evidence regarding early nutritional support in the intensive care unit (ICU) is lacking. We aimed to assess the effect of early nutrition in patients with TBI admitted to the ICU., Methods: Data of adult patients with TBI admitted to the trauma ICU of a regional trauma center in Korea between 2022 and 2023 were retrospectively analyzed. Those with ICU stay <7 days, younger than 18 years, and with underlying diseases that could alter baseline metabolism, were excluded. Nutritional support on day 4 of ICU admission was measured. The patients were classified into mortality and survival groups, and risk factors for mortality were evaluated. Subgroup analyses were performed based on TBI severity., Results: Overall, 864 patients were diagnosed with acute TBI, of whom 227 were included in this study. The mortality rate in the study population was 15% (n=34). Those in the survival group were younger, had longer hospital stays, had a higher initial Glasglow Coma Scale (GCS) score, and had a higher intake of calorie supplements than those in the mortality group. In a subgroup analysis of patients with non-severe TBI (GCS>8), total calorie intake (751.4 vs 434.2 kcal, p=0.029), total protein intake (37.5 vs. 22.1 g, p=0.045), and ratio of supplied to target calories (0.49 vs 0.30, p=0.047) were higher in the survival group than in the mortality group. Logistic regression analysis revealed that calorie intake (B=-0.002, p=0.040) and initial hemoglobin level (B=-0.394, p=0.005) were risk factors for mortality in patients with non-severe TBI., Conclusion: More calories were supplied to the survival group than the mortality group among patients with TBI. Additionally, logistic regression analysis showed that increased calorie supply was associated with reduced mortality in patients with non-severe TBI. The mortality group had low protein intake; however, this did not emerge as a risk factor for mortality. Early sufficient nutritional support improves the prognosis of patients with TBI.

Importance: Little is known about the impact of different anesthetic agents used for routine magnetic resonance imaging (MRI) sedation on pulmonary function in children., Objective: To compare the incidence of pulmonary atelectasis after MRI sedation with propofol vs propofol-ketamine., Design, Setting, and Participants: This double-masked randomized clinical trial screened 117 consecutive pediatric patients aged 3 to 12 years with American Society of Anesthesiologists physical status I to II undergoing elective MRI under deep sedation from November 2, 2022, to April 28, 2023, at a tertiary referral center. Four patients met the exclusion criteria, and 5 patients refused to participate. The participants and outcome assessors were masked to the group allocation., Interventions: During the MRI, the propofol group received 0.2 mL/kg of 1% propofol and 2 mL of 0.9% saline followed by a continuous infusion of propofol (200 μg/kg/min) and 0.9% saline (0.04 mL/kg/min). The propofol-ketamine group received 0.2 mL/kg of 0.5% propofol and 1 mg/kg of ketamine followed by a continuous infusion of propofol (100 μg/kg/min) and ketamine (20 μg/kg/min)., Main Outcome and Measure: The incidence of atelectasis assessed by lung ultrasonography examination., Results: A total of 107 children (median [IQR] age, 5 [4-6] years; 62 male [57.9%]), with 54 in the propofol group and 53 in the propofol-ketamine group, were analyzed in this study. Notably, 48 (88.9%) and 31 (58.5%) patients had atelectasis in the propofol and propofol-ketamine groups, respectively (relative risk, 0.7; 95% CI, 0.5-0.8; P < .001). The incidence of desaturation and interruption of the MRI due to airway intervention or spontaneous movement did not significantly differ between the groups. The propofol-ketamine group showed a faster emergence time than the propofol group (15 [9-23] vs 25 [22-27] minutes in the propofol-ketamine vs propofol group; median difference in time, 9.0 minutes; 95% CI, 6.0-12.0 minutes; P < .001). No patient was withdrawn from the trial due to adverse effects., Conclusions and Relevance: In this randomized clinical trial, the propofol-ketamine combination reduced sedation-induced atelectasis while allowing for faster emergence compared with propofol alone., Trial Registration: cris.nih.go.kr Identifier: KCT0007699.

Introduction: Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive malignancy originating in the nasal cavity and paranasal sinuses. Its pathogenesis and immune characteristics remain poorly understood., Objectives: This study investigates the molecular aspects of SNUC, focusing on tumorigenesis and immunity., Methods: For this purpose, spatial transcriptome analysis was employed to compare the gene expression profiles of SNUC tumor cells with those of normal epithelial cells, as well as to compare tumor-infiltrating immune cells with immune cells from normal, tumor-free tissue areas. For validation, next-generation sequencing tests and clinical sample studies were conducted., Results: Spatial transcriptome analysis revealed notable upregulation of EZH2 and the histone family gene such as H3C2 (H3-clustered histone 2) in SNUC tumor cells. Additionally, gene set enrichment analysis identified significant activations in the histone deacetylase (HDAC) signaling pathway, histone acetyltransferase (HAT) pathway, polycomb repressive complex 2 (PRC2), and DNA methylation pathways. A notable decrease was observed in downregulated genes and pathways, including the mucin family of protein genes, the keratin protein gene, and the mucin glycosylation pathway. Next-generation sequencing did not reveal specific genetic mutations within these pathways, although mutations such as IDH2 R172S were noted. Clinical SNUC tissues confirmed increased immunoexpression of EZH2 and PRC2 markers. Analysis of tumor immunity revealed a characteristic immune cell signature, with a notable predominance of naïve B cells, macrophages, CD8 memory T cells, and Tregs in the SNUC microenvironment, alongside the increased expression of LAG3 in tumor-infiltrating immune cells., Conclusion: Our study suggests epigenetic mechanisms, particularly via EZH2, play a crucial role in SNUC carcinogenesis. Furthermore, distinctive immune cell profiles in SNUC point to potential immune-related characteristics of this malignancy., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The evolution of SARS-CoV-2, which limits public control and treatment, seems to have occurred through multiple mechanisms, including recombination of cocirculating strains in hosts. However, insufficient experimental data have been obtained after coinfection. Therefore, we investigated the emergence of variants after coinfection with parental SARS-CoV-2 and the SARS-CoV-2 Delta. We found that fewer (approximately 50%) mutations accumulated in Calu-3 cells than in other cells after serial passaging. Previously, we established a long-term replication mouse model by infecting Calu-3 cell-derived xenograft tumors with SARS-CoV-2. Here, we utilized our model to investigate the outcome after coinfection. More diverse viral mutations, along with multiple high-frequency simultaneous mutations, were discovered in the tumors than during cell passaging. Viral isolates from the tumors showed no cytopathic effects and formed much smaller plaques. Phylogenetic analysis suggested that the genetic makeup of the variants remained largely the same as that of parental SARS-CoV-2 rather than the SARS-CoV-2 Delta. Viral challenge revealed that the isolates were less lethal than the parental SARS-CoV-2 and SARS-CoV-2 Delta strains. These findings suggest that parental SARS-CoV-2 predominates over the SARS-CoV-2 Delta when coinfected, but the SARS-CoV-2 Delta contributes to the evolution of parental SARS-CoV-2 variants toward better host adaptation without recombination., (© 2024 Wiley Periodicals LLC.)

Challenges in minimally invasive surgeries, such as intramedullary nailing for long bone fractures, include radiation overexposure for patients and surgeons, potential malreduction, and physical burden on surgeons in maintaining the reduction status. A robotic bone fracture reduction system was developed in this study to address these problems. The system consists of a hexapod with six degrees of freedom, with a fracture reduction device and a master device. This study aimed to evaluate the novel system in a preclinical setting. The length of the six axes in the system can be adjusted to precisely control the length, angle, and rotation so that no additional traction is required. Fluoroscopic images can be remotely examined to reduce the risk of radiation exposure for surgeons. In this study, alignment accuracy and radiation exposure were measured using 32 bovine bone fracture models, and these surgical outcomes were compared to those of conventional manual surgery to verify the clinical usability and effectiveness of the system. The alignment accuracy was assessed by analyzing length, angulation, and rotation. The four surgeons participating in this study were divided into two groups (expert and novice) according to their clinical experience. All parameters in robotic surgery significantly decreased by approximately 4 mm and 8° on average (p ≤ 0.05) compared to conventional surgery. The mean radiation exposure in robot-assisted surgery was 0.11 mSv, showing a significant decrease compared to conventional surgery (p < 0.05). Reduction accuracy was higher in robotic surgery performed by the novice group than in conventional surgery performed by the expert group; however, standard deviation values were inversed. In conclusion, the bone fracture reduction robot system increased the alignment accuracy through precise control while reducing radiation exposure in surgeons, as the surgery was performed remotely. The use of this system is predicted to improve the accuracy and reproducibility of the surgery and the safety of medical staff. 1 ., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)

The current study examines the relationships between teachers' job-demands and resources, perceived stress, job burnout, and depressive symptoms through an online survey administered to early childhood education (ECE: n = 143) and early childhood special education (ECSE: n = 121) teachers in a western state of the United States. Results showed no difference between ECE and ECSE teachers in their levels of job-demands, resources, perceived stress, job burnout, and depressive symptoms. Both ECE and ECSE teachers' job-related stressors were positively related to their perceived stress, and their job commitment was negatively associated with job burnout. However, there were some differences in the correlates of job burnout between ECE and ECSE teachers. For ECE teachers, the number of children with disabilities and their teaching efficacy predicted their job burnout, whereas with ECSE teachers, job-related stressors and the supportiveness of school climate (or the lack thereof) were indirectly related to their job burnout through their perceived stress. The current study suggests that providing professional development for these teachers and enhancing a school's supportive climate will promote the well-being of both ECE and ECSE teachers., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Micronutrient deficiencies are common in inflammatory bowel disease (IBD). The aim of this study was to evaluate micronutrient deficiencies and identify muscular status of patients with IBD. From June 2019 to October 2021, a total of 105 patients with IBD were enrolled prospectively. To obtain objective data, micronutrients were measured in the patients' serum, and body composition analysis was performed using bioelectrical impedance analysis. There were 51 patients with ulcerative colitis (UC) and 54 with Crohn's disease (CD), while the gender ratio (M: F) was 54:51. The average age was 37 ± 18 years, which was significantly lower in patients with CD than UC (29 ± 16 vs. 45 ± 16, p < 0.001). Iron and magnesium were lower in patients with CD compared to UC, respectively (63.3 ± 42.5 vs. 82.8 ± 44.0 µg/dL, p = 0.024, 2.08 ± 0.15 vs. 2.15 ± 0.19 mg/dL, p = 0.036). Vitamin D levels showed insufficiency in patients with UC and deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567). In the UC and CD patient groups, skeletal muscle index (SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC (SMI: 32.8 ± 4.7 vs. 35.8 ± 5.5%, p < 0.004, adjusted skeletal muscle: 7.0 ± 1.5 vs. 8.2 ± 1.9 kg/m 2 , p < 0.001). In conclusion, decreased trace elements, specifically iron, magnesium, and vitamin D, as well as skeletal muscle mass were observed to be prominent in patients with CD as compared to UC.

Air pollution, particularly fine particulate matter less than 2.5 μm in diameter (PM 2.5 ), contributes to respiratory and cardiovascular diseases and poses significant public health risks worldwide. This study evaluated the short-term effects of PM 2.5 on hospital admissions for cardiovascular and respiratory diseases, with additional analyses to identify vulnerable populations based on regional characteristics. The present study analyzed data from 249 Korean communities between 2006 and 2021. Data on daily hospital admissions for cardiovascular and respiratory diseases were obtained from the National Health Insurance Service. Data on PM 2.5 concentrations were sourced from air quality modeling. Additional data on regional characteristics, including the regional deprivation index, proportion of elderly residents, education levels, and greenness levels, were also collected. We used case time series analysis to assess the associations between PM 2.5 concentrations and hospital admissions for cardiovascular and respiratory diseases and explored effect modification by regional characteristics with stratified analyses. The mean numbers of daily cardiovascular admissions and respiratory admissions were 5.68 ± 5.46 and 6.46 ± 8.03, respectively. The mean PM 2.5 concentrations were 23.58 ± 13.66 μg/m 3 . A10 μg/m³ increment in daily PM 2.5 concentration was associated with increase of cardiovascular and respiratory hospitalization by 0.94% (95% CI: 0.84%, 1.04%) and 1.43% (95% CI: 1.34%, 1.52%), respectively. Regional characteristics analysis showed significant disparities, with higher risks for hospital admissions in areas with lower deprivation and low greenness. This study highlights the significant short-term health impacts of PM 2.5 on respiratory and cardiovascular hospital admissions in Korean communities. The findings underscore the critical role of regional and demographic factors in modulating these effects, identifying socio-economic areas, age structure of the population, lower education levels, and low greenness as key vulnerability factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the plastic effects of parieto-motor (PAR-MOT) cortico-cortical paired associative paired stimulation (cc-PAS) in patients with two forms of focal dystonia, writer's cramp and cervical dystonia, compared to healthy volunteers (HVs)., Methods: We used cc-PAS to induce associative plasticity using repeated time-locked paired transcranial magnetic stimulation (TMS) pulses over the parietal and motor cortices in 16 patients with writer's cramp (WC), 13 patients with cervical dystonia (CD), and 23 healthy volunteers. We measured parieto-motor corticocortical connectivity using posterior parietal cortex (PPC) to primary motor cortex (M1) facilitation and input-output curves (IOC) of the motor-evoked potential (MEP) before and after PAR-MOT cc-PAS. The PAR-MOT cc-PAS consisted of 100 pairs of TMS pulses every 5 s, with the conditioning pulse applied to the left angular gyrus in the intraparietal sulcus and the test pulse applied to the M1 hotspot of the first dorsal interosseous muscle., Results: The cc-PAS increased the area under the IOC by increasing its maximum level in patients with WC but not in patients with CD or healthy volunteers. The cc-PAS had no significant effect on other IOC parameters. There were no significant differences in PPC to M1 facilitation changes after PAR-MOT cc-PAS among all groups., Conclusions: This study suggests that PAR-MOT cc-PAS abnormally increases M1 excitability in patients with WC but not in those with CD. Additionally, this increased plastic response in patients with WC does not appear to be directly linked to PPC to M1 corticocortical connectivity., Competing Interests: Declaration of competing interest All authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Study Design: Retrospective magnetic resonance imaging grading with comparison between experts and deep convolutional neural networks (CNNs)., Objective: The application of deep learning to clinical diagnosis has gained popularity. This approach can accelerate image interpretation and serve as a screening tool to help doctors., Methods: A comparison was conducted between retrospective magnetic resonance imaging (MRI) grading performed by experts and grading obtained using CNN classifiers. Data were collected from the lumbar axial dataset in the DICOM format. Two experts labeled the sampled images using the same diagnostic tools: localization of patches near the spinal canal, rootlet leveling, and stenosis grading. Comprehensive comparisons were presented for both rootlet cord classification and stenosis grading., Results: Rootlet-cord classification for the two analyzers was 90.3% and the F1 score was 86.6%. The agreement of Analyzers-Classifiers was 92.7% and 96.8% for data with 90.6% and 95.6% F1 scores, respectively. For stenosis grading, there was an agreement of 89.2% between the two analyzers, resulting in an F1 score of 76.5%. The grades of the Analyzers-Classifiers agreed on 91.5/89.4% of the data, with an F1 score of 78.4/75.7%. Analyzer1 and Analyzer2 classified >74% as grade A (78.8% and 74.4%, respectively), 15.4% and 18.6% as grade B, 4.2% and 6.0% as grade C, and 1.6% and 2.0% as grade D, respectively., Conclusions: The fully automated deep learning model showed competitive results in stenosis grade diagnosis and rootlet cord classification under similar anatomical conditions. However, abrupt anatomical changes can lead to a puzzle diagnosis based only on images., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aim: Endoscopic submucosal dissection (ESD) effectively treats selected early gastric cancers (EGCs). However, the association of microsatellite instability (MSI), Epstein-Barr virus (EBV), p53, and β-catenin status with clinicopathologic parameters in EGCs treated with ESD have not been well studied., Patients and Methods: We retrospectively collected 312 consecutive EGC cases treated with ESD from January 2021 to December 2023 at Kyungpook National University Chilgok Hospital. MSI polymerase chain reaction, EBV encoded RNA in situ hybridization, and p53 and β-catenin immunostaining were performed for all cases., Results: Among 312 EGC cases, there were 42 MSI-High (MSI-H) cases (13.5%), 13 EBV-associated gastric cancer (EBVaGC) cases (4.2%), 249 intestinal type cases (79.8%), and eight poorly cohesive carcinoma cases (2.6%). MSI-H was significantly associated with lymphovascular invasion (p=0.02), local recurrence (p=0.03), and synchronous tumors (p<0.001). More than half of EBVaGC cases showed submucosal invasion (61.5%, 8/13) (p=0.016). Consequently, non-curative ESD was more frequently found in EBVaGC than in other subtypes (p<0.001). Mutant p53 patterns and nuclear translocation of β-catenin were almost exclusively found in the intestinal type (p<0.001), without association with clinicopathologic parameters. Margin involvement was frequent in poorly cohesive carcinoma (p=0.003)., Conclusion: We demonstrated that MSI-H and EBVaGC are strongly associated with clinicopathologic parameters and risk factors in EGCs treated with ESD. Molecular testing of gastric cancers should be considered before ESD for better patient management., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Liver cirrhosis is a severe chronic disease that results from various etiological factors and leads to substantial morbidity and mortality. Alcoholic cirrhosis (AC) and non-AC (NAC) arise from prolonged and excessive consumption of alcohol and metabolic syndromes, respectively. Precise molecular mechanisms of AC and NAC are yet to be comprehensively understood for diagnostics and therapeutic advances to materialize. This study reports novel findings to this end by utilizing high-throughput RNA sequencing and microarray data from the Gene Expression Omnibus (GEO). We performed a meta-analysis of transcriptomics data to identify the differentially expressed genes specific to AC and NAC. Functional enrichment and protein-protein interaction network analyses uncovered novel hub genes and transcription factors (TFs) critical to AC and NAC. We found that AC is primarily driven by metabolic dysregulation and oxidative stress, with key TFs such as RELA, NFKB1, and STAT3. NAC was characterized by fibrosis and tissue remodeling associated with metabolic dysfunction, with TFs including USF1, MYCN, and HIF1A. Key hub genes such as ESR1 , JUN , FOS , and PKM in AC, and CD8A , MAPK3 , CCND1 , and CXCR4 in NAC were identified, along with their associated TFs, pointing to potential therapeutic targets. Our results underscore the unique and shared molecular mechanisms that underlie AC and NAC and inform the efforts toward precision medicine and improved patient outcomes in liver cirrhosis.

Objectives: This study aimed to determine whether fetal subcutaneous tissue (SCT) thickness, measured using ultrasound immediately before and after delivery, can reflect changes in glucose metabolism immediately after delivery. We also evaluated the impact of insulin resistance changes during pregnancy by comparing pregnant women with well-controlled gestational diabetes mellitus (GDM) and those with normal glucose metabolism., Study Design: The study participants were 117 pregnant women, including 97 controls and 20 patients with GDM who visited our obstetric clinic between February and December 2022. The participants were scheduled for cesarean delivery at a gestational age of ≥37 weeks. SCT thickness before delivery was measured using ultrasound and within 48 h after delivery using Holtain calipers. The glucose and insulin concentrations were quantified from cord blood collected immediately after delivery. Based on these results, a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was performed to assess insulin resistance. Independent t-test or Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables were used to compare the various parameters. Correlations among the variables in each group were assessed by calculating the correlation coefficient (Pearson's correlation)., Results: SCT thickness measured using ultrasound and calipers demonstrated a strong correlation where pregnant women with GDM exhibited thicker fetal SCT and neonate skinfolds than in those without GDM. Glucose and insulin levels in the cord blood were significantly elevated (p < 0.05) in the gestational diabetic group, along with remarkable differences (p < 0.001) in HOMA-IR. These variables indicated a higher prevalence of glucose intolerance in the neonates of mothers with GDM. In pregnant women with GDM, there was a statistically significant correlation between fetal abdominal SCT thickness and glucose levels (r = 0.64, p < 0.01) and HOMA-IR (r = 0.48, p < 0.05)., Conclusions: Measuring the subcutaneous fat thickness of the fetus shortly before delivery is beneficial for predicting insulin resistance in neonates. This is considered particularly useful for women with effectively managed GDM, where the presence of conditions such as macrosomia may not be pronounced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The study aimed to investigate the clinical outcomes of fetuses diagnosed with isolated mega cisterna magna in utero. Methods: A multicenter retrospective cohort study was conducted across 18 university hospitals from 2010 to 2019. Cases diagnosed with isolated mega cisterna magna, defined as a cisterna magna >10 mm with a normal cerebellar vermis and no cystic dilation of the fourth ventricle, were included. Cases with other central nervous system (CNS) anomalies, extra-central nervous system anomalies, chromosomal abnormalities, or congenital infections were excluded. Maternal demographics, prenatal findings, delivery outcomes, and postnatal outcomes were analyzed. Results: The mean gestational age at initial diagnosis was 28.6 ± 3.9 weeks, and the mean anteroposterior diameter of the cisterna magna was 12.5 ± 3.2 mm. Of the 71 cases initially assessed, 48 (67.6%) showed self-regression in utero. Postnatally, 13 cases (18.3%) had persistent isolated mega cisterna magna, whereas 10 cases (14.1%) were diagnosed with other central nervous system anomalies. Among the persistent isolated mega cisterna magna cases, one child exhibited delayed neurodevelopment. There was a higher incidence of isolated mega cisterna magna in male fetuses, which exhibited a significantly larger mean cisterna magna diameter compared with female fetuses ( P  = .045). Conclusion: Male fetuses exhibited a higher incidence of isolated mega cisterna magna compared with female fetuses and had larger anteroposterior diameters of the cisterna magna. The study demonstrated favorable neurodevelopmental outcomes associated with isolated mega cisterna magna, with self-regression observed in two-thirds of the cases. However, consecutive prenatal and postnatal evaluations for additional central nervous system or extra-central nervous system malformations need to be performed, considering the differences between prenatal and postnatal diagnoses., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment., Methods: In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15-associated digestive malignancies., Results: The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies., Conclusions: This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE -/- mouse model treated with P. gingivalis LPS., Methods: The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE -/- mice through injections of P. gingivalis LPS, RC-3095, or a combination of both., Results: RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE -/- mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis., Conclusions: RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: This study aims to evaluate the safety and efficacy of a short-term, low dose, weight-based subcutaneous enoxaparin protocol (SEP) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis., Methods: Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied., Results: The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days ( p  < 0.001). After adjusting for the type of thrombolytic agent, use of adjunct thrombectomy device, cutting balloon, drug-coated balloon, and stent graft, SEP remained a significant factor associated with longer thrombosis-free patency (HR 0.166: 95% CI 0.070-0.392, p  < 0.001)., Discussion: SEP appears to be a feasible and safe thromboprophylaxis method to improve thrombosis-free patency for AV access with recurrent thrombosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectrometry. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. The WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA subtype A receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep-inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Exposure to air pollution poses a risk to human respiratory health, and a preventive and therapeutic remedy against fine dust-induced respiratory disease is needed., Background/objectives: The respiratory-protective effects of Lysimachia mauritiana (LM) against airway inflammation were evaluated in a mouse model exposed to a fine dust mixture of diesel exhaust particles and particulate matter with a diameter of less than 10 µm (PM10D)., Methods: To induce airway inflammation, PM10D was intranasally injected into BALB/c mice three times a day for 12 days, and LM extracts were given orally once per day. The immune cell subtypes, histopathology, and expression of inflammatory mediators were analyzed from the bronchoalveolar lavage fluid (BALF) and lungs., Results: LM alleviated the accumulation of neutrophils and the number of inflammatory cells in the lungs and the BALF of the PM10D-exposed mice. LM also reduced the release of inflammatory mediators (MIP-2, IL-17, IL-1α, CXCL1, TNF-α, MUC5AC, and TRP receptor channels) in the BALF and lungs. Lung histopathology was used to examine airway inflammation and the accumulation of collagen fibers and inflammatory cells after PM10D exposure and showed that LM administration improved this inflammation. Furthermore, LM extract inhibited the MAPK and NF-κB signaling pathway in the lungs and improved expectoration activity through an increase in phenol red release from the trachea., Conclusions: LM alleviated PM10D-exposed neutrophilic airway inflammation by suppressing MAPK/NF-κB activation. This study indicates that LM extract may be an effective therapeutic agent against inflammatory respiratory diseases.

Salmonella is a rare causative pathogen of osteomyelitis and is commonly detected in patients with sickle cell disease. We described 2 consecutive cases of nontyphoidal Salmonella osteomyelitis identified in immunocompetent children. It is evident that even children without apparent risk factors for immune dysfunctions can be affected, so maintaining clinical suspicion is crucial for early diagnosis and prompt treatment., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lateral flow assay (LFA) systems use metal nanoparticles for rapid and convenient target detection and are extensively studied for the diagnostics of various diseases. Gold nanoparticles (AuNPs) are often used as probes in LFAs, displaying a single red color. However, there is a high demand for colorimetric LFAs to detect multiple biomarkers, requiring the use of multicolored NPs. Here, we present a highly sensitive multiplexed colorimetric lateral flow immunoassay by multicolored Plasmon-controlled metal-silica Isoform Nanocomposites (PINs). We utilized the localized surface plasmon resonance effect to create multi-colored PINs by precisely adjusting the distance between the NPs on the surface of PINs through the controlled addition of reduced gold and silver precursors. Through simulations, we also confirmed that the distance between nanoparticles on the surface of PINs significantly affects the color and colorimetric signal intensity of the PINs. We achieved multicolored PINs that exhibit stronger colorimetric signals, offering a new solution for LFA detection with high sensitivity and a 33 times reduced limit of detection (LOD) while maintaining consistent size deviations within 5%. We expect that our PINs-based colorimetric LFA will facilitate the sensitive and simultaneous detection of multiple biomarkers in point-of-care testing., (© 2024. The Author(s).)

Background: Patients often struggle with determining which outpatient specialist to consult based on their symptoms. Natural language processing models in health care offer the potential to assist patients in making these decisions before visiting a hospital., Objective: This study aimed to evaluate the performance of ChatGPT in recommending medical specialties for medical questions., Methods: We used a dataset of 31,482 medical questions, each answered by doctors and labeled with the appropriate medical specialty from the health consultation board of NAVER (NAVER Corp), a major Korean portal. This dataset includes 27 distinct medical specialty labels. We compared the performance of the fine-tuned Korean Medical bidirectional encoder representations from transformers (KM-BERT) and ChatGPT models by analyzing their ability to accurately recommend medical specialties. We categorized responses from ChatGPT into those matching the 27 predefined specialties and those that did not. Both models were evaluated using performance metrics of accuracy, precision, recall, and F 1 -score., Results: ChatGPT demonstrated an answer avoidance rate of 6.2% but provided accurate medical specialty recommendations with explanations that elucidated the underlying pathophysiology of the patient's symptoms. It achieved an accuracy of 0.939, precision of 0.219, recall of 0.168, and an F 1 -score of 0.134. In contrast, the KM-BERT model, fine-tuned for the same task, outperformed ChatGPT with an accuracy of 0.977, precision of 0.570, recall of 0.652, and an F 1 -score of 0.587., Conclusions: Although ChatGPT did not surpass the fine-tuned KM-BERT model in recommending the correct medical specialties, it showcased notable advantages as a conversational artificial intelligence model. By providing detailed, contextually appropriate explanations, ChatGPT has the potential to significantly enhance patient comprehension of medical information, thereby improving the medical referral process., (©Eunbeen Jo, Hakje Yoo, Jong-Ho Kim, Young-Min Kim, Sanghoun Song, Hyung Joon Joo. Originally published in JMIR Formative Research (https://formative.jmir.org), 18.10.2024.)

Purpose: We aimed to investigate the effects of Fresnel prism treatment for small-angle esotropia (≤ 20 prism diopters [PD]) with fixation preference., Methods: We included 32 patients with remaining esotropia ≤ 20 PD measured using the simultaneous prism and cover test (SPCT) after full refractive error correction. Fresnel prism was applied to make patients orthotropic with glasses. Treatment was discontinued if remaining esotropia ≤ 4 PD was sustained during two consecutive follow-ups (2-month intervals) or if the angle continued to increase with prism adaptation. Patients were divided into treatment success and failure groups. Treatment success was defined by motor and visual acuity (VA) aspects. Criteria for motor success was residual esotropia ≤ 8 PD in patients with initial esotropia > 8 PD and a 30% decrease of esotropia in those with initial esotropia ≤ 8 PD. VA success was improvement of > 0.2 logMAR in the non-dominant eye., Results: The initial esodeviation angle was 6.92 ± 4.66 PD at distance and 10.53 ± 5.58 at near. The logMAR VA was 0.10 ± 0.13 and 0.26 ± 0.20 in the dominant and non-dominant eye, respectively. Among the 32 patients, 14 showed motor success. Among 26 patients whose VA could be measured, 15 showed VA success. Factors influencing motor success were a small amount of maximum prescribed Fresnel prism, less frequent need for Fresnel prism adaptation, and high percentage of achieving orthotropia with Fresnel prism treatment. VA success was influenced by low frequency of anisometropia and the small amount of maximum prescribed Fresnel prism., Conclusion: Fresnel prism could be a non-invasive treatment option for some patients with small-angle esotropia with fixation preference., Key Messages: What is known The optimal approach for addressing small-angle esotropia is a topic of debate. Not much research has been conducted on Fresnel prism treatment in patients with small-angle esotropia. What is new Motor success and visual acuity improvement were observed in some patients undergoing Fresnel prism treatment. Factors contributing to motor success were the small maximum angle of esodeviation, the less frequent necessity for Fresnel prism adaptation, and the achievement of orthotropia during Fresnel prism treatment. Visual acuity improvement was hindered by the presence of anisometropia and the large maximum prescribed amount of Fresnel prism. Fresnel prism treatment can be used as a treatment option for some patients with small-angle esotropia with fixation preference., (© 2024. The Author(s).)