Comparing Gut Microbial Composition and Functional Adaptations between SPF and Non-SPF pigs.

The gut microbiota is closely associated with digestion, metabolism, immunity, and host health. The imbalance of the microbial community in livestock directly affects their well-being and, consequently, productivity. The composition and diversity of the gut microbiota are influenced not only by host genetics but also by environmental factors such as the microbial complexity of the rearing environment, feeds, and antibiotics. Here, we focus on the comparison of gut microbial communities in miniature pigs developed for xenotransplantation in specific pathogen-free (SPF) and conventional (non-SPF) facilities. To identify the disparities in gut microbial composition and functionality between these two environments, 16S RNA metagenome sequencing was conducted using fecal samples. The results revealed that the non-SPF pigs had higher gut microbiota diversity than the SPF pigs. The genera Streptococcus and Ruminococcus were more abundant in SPF pigs than in non-SPF pigs. Blautia, Bacteroides, and Roseburia were exclusively observed in SPF pigs, whereas Prevotella was exclusively found in non-SPF pigs. Carbohydrate and nucleotide metabolism, as well as environmental information processing, were predicted to be enriched in SPF pigs. In addition, energy and lipid metabolism, along with processes related to genetic information, cellular communication, and diseases, were predicted to be enriched in non-SPF pigs. This study makes an important contribution to elucidating the impact of environments harboring a variety of microorganisms, including pathogens, on the gut microbiota of miniature pigs. Furthermore, we sought to provide foundational data on the characteristics of the gut microbiota in genetically modified pigs, which serve as source animals for xenotransplantation.

Enhancement of hyaline cartilage and subchondral bone regeneration in a rat osteochondral defect model through focused extracorporeal shockwave therapy.

Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-ß, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-ß, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion: ESWT promoted the effect of TGF-ß/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model.

Natural peloids originating from subsea depths of 200 m in the hupo basin, South Korea: physicochemical properties for potential pelotherapy applications.

The present study firstly reports surface sediment from the subsea depth of 200 m as a potential natural peloid. The fine-silt sediment exhibited a consistent clay mineral composition dominated by illite, chlorite, kaolinite, and diatomite. The most abundant clay mineral was illite/mica, with other minerals loosely packed in a face-to-face orientation. The thermal conductivity, specific heat capacity, and cation-exchange capacity of the sediment were in the range 0.855-0.885 W/m K, 2.718-2.821 J/g °C, and 23.06-32.96 cmol/kg, respectively. The concentrations of most toxic elements in the sediment were considerably lower than the limits set by domestic cosmetic regulations and other international standards. The analyzed samples exhibited similar properties to those of previously reported peloids, thus making them suitable for use in the field of pelotherapy; furthermore, the consistency in data across a wide peloid-distribution area is expected to enable economically viable mining. Future investigations should aim to to evaluate the long-term effects on the skin, the bioavailability of potentially hazardous substances, and the therapeutic efficacy for various skin conditions.

Structure-Guided Engineering of Thermodynamically Enhanced SaCas9 for Improved Gene Suppression.

Proteins with multiple domains play pivotal roles in various biological processes, necessitating a thorough understanding of their structural stability and functional interplay. Here, a structure-guided protein engineering approach is proposed to develop thermostable Cas9 (CRISPR-associated protein 9) variant for CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference applications. By employing thermodynamic analysis, combining distance mapping and molecular dynamics simulations, deletable domains are identified to enhance stability while preserving the DNA recognition function of Cas9. The resulting engineered Cas9, termed small and dead form Cas9, exhibits improved thermostability and maintains target DNA recognition function. Cryo-electron microscopy analysis reveals structural integrity with reduced atomic density in the deleted domain. Fusion with functional elements enables intracellular delivery and nuclear localization, demonstrating efficient gene suppression in diverse cell types. Direct delivery in the mouse brain shows enhanced knockdown efficiency, highlighting the potential of structure-guided engineering to develop functional CRISPR systems tailored for specific applications. This study underscores the significance of integrating computational and experimental approaches for protein engineering, offering insights into designing tailored molecular tools for precise biological interventions.

Biological network comparison identifies a novel synergistic mechanism of Ginseng Radix-Astragali Radix herb pair in cancer-related fatigue.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. AIM OF THE STUDY: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. CONCLUSION: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Anti-Melanogenic and Anti-Inflammatory Effects of 2'-Hydroxy-4',6'-dimethoxychalcone in B16F10 and RAW264.7 Cells.

Chalcone is a type of flavonoid compound that is widely biosynthesized in plants. Studies have shown that consuming flavonoids from fruits and vegetables or applying individual ingredients reduces the risk of skin disease. However, the effects of chalcone on melanogenesis and inflammation have not been fully investigated. The aim of this study was to evaluate the anti-melanogenic and anti-inflammatory effects of 2'-hydroxy-3,4'-dimethoxychalcone (3,4'-DMC), 2'-hydroxy-4,4'-dimethoxychalcone (4,4'-DMC), 2'-hydroxy-3',4'-dimethoxychalcone (3',4'-DMC), and 2'-hydroxy-4',6'-dimethoxychalcone (4',6'-DMC). Among the derivatives of 2'-hydroxy-4'-methoxychalcone, 4',6'-DMC demonstrated the most potent melanogenesis-inhibitory and anti-inflammatory effects. As evidenced by various biological assays, 4',6'-DMC showed no cytotoxicity and notably decreased the expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 enzymes. Furthermore, it reduced cellular melanin content and intracellular tyrosinase activity in B16F10 melanoma cells by downregulating microphthalmia-associated transcription factor (MITF), cAMP-dependent protein kinase (PKA), cAMP response element-binding protein (CREB), p38, c-Jun N-terminal kinase (JNK), ß-catenin, glycogen synthase kinase-3ß (GSK3ß), and protein kinase B (AKT) proteins, while upregulating extracellular signal-regulated kinase (ERK) and p-ß-catenin. Additionally, treatment with 4',6'-DMC significantly mitigated the lipopolysaccharide (LPS)-induced expression of NO, PGE2, inflammatory cytokines, COX-2, and iNOS proteins. Overall, 4',6'-DMC treatment notably alleviated LPS-induced damage by reducing nuclear factor kappa B (NF-κB), p38, JNK protein levels, and NF-kB/p65 nuclear translocation. Finally, the topical applicability of 4',6'-DMC was evaluated in a preliminary human skin irritation test and no adverse effects were found. These findings suggest that 4',6'-DMC may offer new possibilities for use as functional ingredients in cosmeceuticals and ointments.

The Safety Climate and Patient Safety Activities in Mental Health Nurses: The Mediating Effect of Safety Control.

This study aimed to investigate the mediating effect of safety control on the relationship between safety climate and patient safety management activities for mental health nurses. A survey was conducted on 177 nurses working at mental hospitals in G-do from 28 July 2023 to 15 August 2023. Data were analyzed using the SPSS/WIN 27.0 and Sobel test. Significant relationships were found between safety climate and safety control (r = 0.40, p < 0.001), safety climate and patient safety management activities(r = 0.40, p < 0.001), and safety control and patient safety management activities (r = 0.43, p < 0.001). Additionally, safety control partially mediated the safety climate and the patient safety management activities (Z = 3.63, p < 0.001). Therefore, programs that increase safety control and create a safety climate need to be developed to promote patient safety activities of mental health nurses.

Methylmercury exposure at dosage conditions that do not affect growth can impair memory in adolescent mice.

Methylmercury is an environmental pollutant that can induce serious central nervous system damage. Its ubiquitous presence in the environment in trace amounts has raised concerns about potential adverse effects on human health. Although many studies have evaluated the effects of methylmercury on neural development in fetal and neonatal mice, there has been less focus on studies using adolescent mice. Therefore, in this study, the effects of methylmercury on brain neurodevelopment and maturation were evaluated by various neurobehavioral trials using adolescent mice exposed to 30 ppm methylmercuric chloride (approximately 24 ppm methylmercury) for up to 8 weeks. Under these administration conditions, weight gain in adolescent mice was unaffected by methylmercury exposure. Furthermore, methylmercury exposure in adolescent mice had no effect on sociability as assessed by the social interaction test, impulsivity as assessed by the cliff avoidance reaction test, depressive behavior as assessed by the tail-suspension test, or locomotor activity as assessed using the Supermex system. In contrast, short-term memory assessed by the Y-maze test, as well as long-term memory assessed by novel object recognition and passive avoidance tests, revealed impairments induced by methylmercury exposure in adolescent mice. These results suggest that long-term exposure to methylmercury during adolescence potentially impairs memory function, and the nervous pathway of brain areas involved in learning and memory are particularly vulnerable to the adverse effects of methylmercury. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00239-y.

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.

Background: Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. Objectives: We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. Methods: The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Results: Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. Conclusions: In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Pregnancy outcomes of cerclage in twin gestations: a multicenter retrospective cohort study.

OBJECTIVES: To determine the effects of cerclage on twin pregnancies. METHODS: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records. RESULTS: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group (n = 127) and the CL >2.5 cm group (n = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11-2.87; p = .016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30-0.82; p value = .006). CONCLUSIONS: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design.

Expression of Concern.

The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the following articles are under investigation due to concerns raised regarding non-verifiable nucleotide sequences and cell lines used in the following articles: -       Shi YX, Ye BL, Hu BR, Ruan XJ. Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric cancer. Eur Rev Med Pharmacol Sci 2018; 22 (17): 5525-5530-DOI: 10.26355/eurrev_201809_15813-PMID: 30229824. -       Dong SR, Ju XL, Yang WZ. STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2019; 23 (19): 8360-8370-DOI: 10.26355/eurrev_201910_19147-PMID: 31646566. -       Chen J, Yuan ZH, Hou XH, Shi MH, Jiang R. LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2020; 24 (4): 1807-1814-DOI: 10.26355/eurrev_202002_20358-PMID: 32141549. Further updates will be provided once the investigation is completed. The authors have been notified about this expression of concern.

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

Synergistic effects of copper and oxygen vacancies in enhancing the efficacy of partially crystalline CuMnxOy catalyst for ozone decomposition.

To tackle the challenge of ground-level ozone pollution, this study proposed a potential catalytic design approach for ozone decomposition using Cu-Mn bimetallic oxide. This approach is grounded in an understanding of the intrinsic reactivity for catalyst and incorporates a novel potassium-driven low-temperature oxidation process for catalyst synthesis. The research highlights the creation of a highly reactive Cu-Mn oxide phase with extensive defect coverage, leading to significantly increased reaction rates. It also identifies the MnO2(100) facet as a crucial active phase, where oxygen vacancies simultaneously enhance O3 adsorption and decomposition, albeit with a concurrent risk of O2 poisoning due to the stabilization of adsorbed O2. Crucially, the incorporation of Cu offsets the effects of oxygen vacancies, influencing conversion rates and lessening O2 poisoning. The synergistic interplay between Cu and oxygen vacancies elevates the performance of the defect-rich Cu-Mn oxide catalyst. By combining computational and experimental methods, this study not only advances the understanding of the Cu-Mn oxide system for ozone decomposition but also contributes valuable insights into developing more efficient catalysts to mitigate ozone pollution.

Solar Carboxylation Using CO2: Interfacially Synthesized Flexible Covalent Organic Frameworks Film as a Photocatalyst for Highly Selective Solar Carboxylation of Arylamines with CO2.

Carbon dioxide (CO2) conversion into value-added chemicals/fuels by utilizing solar energy is a sustainable way to mitigate our dependence on fossil fuels and stimulate a carbon-neutral economy. However, the efficient and affordable conversion of CO2 is still an ongoing challenge. Here, we report an interfacially synthesized visible-light-active Ni(II)-integrated covalent organic frameworks (TaTpBpy-Ni COFs) film as a photocatalyst for efficient CO2 conversion into carboxylic acid under ambient conditions. Notably, the TaTpBpy-Ni COFs film showed excellent photocatalytic activity for the carboxylation of various arylamines with CO2 to the corresponding arylcarboxylic acid via C-N bond activation under solar-light irradiation. Moreover, this carboxylation protocol exhibits mild reaction conditions and good functional group tolerance without the necessity of using stoichiometric metallic reductants. This work shows a benchmark example of not only the interfacially synthesized COFs film used as a photocatalyst for solar-light energy utilization but also the selective solar chemical production system of arylcarboxylic acid directly from CO2.

High-throughput viable circulating tumor cell isolation using tapered-slit membrane filter-based chipsets in the differential diagnosis of ovarian tumors.

OBJECTIVE: To evaluate the diagnostic performance of circulating tumor cells (CTCs) using tapered-slit membrane filter (TSF)-based chipsets for the differential diagnosis of adnexal tumors. METHODS: A total of 230 women with indeterminate adnexal tumors were prospectively enrolled. The sensitivity, specificity, and accuracy of the CTC-detecting chipsets were analyzed according to postoperative pathological results and compared with those of cancer antigen (CA)-125 and imaging tests. RESULTS: Eighty-one (40.3%) benign tumors, 31 (15.4%) borderline tumors, and 89 (44.3%) ovarian cancers were pathologically confirmed. The sensitivity, specificity, and accuracy of CTC-detecting chipsets (75.3%, 58.0%, and 67.1%) for differentiating ovarian cancer from benign tumors were similar to CA-125 (78.7%, 53.1%, and 66.5%), but lower than CT/MRI (94.2%, 77.9%, and 86.5%). "CTC or CA125" showed increased sensitivity (91.0%) and "CTC and CA-125" revealed increased specificity (77.8%), comparable to CT/MRI. CTC detection rates in stage I/II and stage III/IV ovarian cancers were 69.6% and 81.4%, respectively. The sensitivity to detect high-grade serous (HGS) cancer from benign tumors (84.6%) was higher than that to detect non-HGS cancers (68.0%). CONCLUSION: Although the diagnostic performance of the TSF platform to differentiate between ovarian cancer and benign tumors did not yield significant results, the combination of CTC and CA-125 showed promising potential in the diagnostic accuracy of ovarian cancer.

Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.