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Herein, the dimensions of the interphase and tunneling zones are utilized to develop a model for the conductivity of polymer composites with carbon nanofiber (CNF) named as PCNFs. The effective CNF concentration and percolation onset depend on the interphase depth to estimate the concentration of the CNF/interphase network. Additionally, the length and diameter of tunnels are considered to account for tunneling resistance in the developed model. Accordingly, the current model assumes simple, measurable, and effective factors to estimate the conductivity of PCNF. Parametric analyses and experimental data of conductivity for real examples are used to validate the developed model. A very thin interphase (t = 5 nm) and high percolation onset (ϕp = 0.03), as well as large tunnels (λ > 10 nm) and small contact diameters (d

In this study, a multi-scale method is developed using simple equations and meaningful factors to estimate the effective conductivity of carbon nanofiber (CNF) polymer composites, referred to PCNFs. The interphase around the networked nanofibers is considered in Step I, while the tunneling zone near the CNF/interphase is addressed in Step II. Finally, the effective conductivity of PCNFs, comprising CNFs, interphase, and tunnels, is estimated in Step III. The calculations of the multi-step method are validated by plotting the impacts of all factors and comparing them with experimental data from numerous CNF-filled samples. The minimum ranges of percolating onset (ϕp) and polymer resistivity in the tunnel (ρ) maximize the effective conductivity of system, but an insulative sample is observed at ρ > 60 Ω m and ϕp > 0.015. Additionally, a tunneling distance (λ) of 1 nm and a contact diameter (d) of 60 nm yield the uppermost effective conductivity of 0.45 S/m, though d

Abstract The BRCA1/2 pathogenic variant (PV) increases the risk of breast and ovarian cancer; thus, risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) are recommended. We evaluated the effects of the graphical display of cancer risk compared with those of numerical presentation on the decision-making for risk-reducing (RR) surgery. A total of 471 women representing the Korean population were recruited. The lifetime risk of breast/ovarian cancer were given numerically followed by graphically in hypothetical BRCA1/2 PV-positive cases. Subsequently, the study participants were asked for their willingness to undergo RRSO/RRM. When the ovarian cancer risk was shown as 44.0%, the percentage of study participants who chose RRSO was 41.0% after numerical presentation versus 39.9% after graphical display, of which the difference was not significant. When the breast cancer risk was presented as 72.0%, 30.4% of the participants opted for RRM under numerical presentation, whereas this increased to 38.6% under graphical display, of which the difference was significant (p

Abstract This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC10 value is less than − 9) and androgen receptor antagonist (log IC30 value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

The existing models for the electrical conductivity of polymer composites with carbon nanofiber (CNF) called as PCNFs are incomplete, thereby limiting their optimization. In this study, the Hui-Shia model is simplified and advanced to accurately foresee the PCNF conductivity by incorporating the main features of CNFs, interphase, and tunnels. The volume fraction of the CNF/interphase network is derived based on the onset of percolation and effective CNF content, while the total conductivity of CNF and tunnels is expressed through tunneling properties. The developed model is evaluated using experimental data from various PCNF systems and through parametric analyses. Theoretical and experimental results demonstrate good agreement, validating the developed model. An insulative PCNF is observed at a CNF radius (R) greater than 90 nm and an interphase depth (t) less than 11 nm. Conversely, the maximum conductivity of 1.5 S/m is achieved with the thinnest CNFs (R = 40 nm) and the thickest interphase (t = 40 nm). Furthermore, very small contact diameters (d less than 17 nm) do not result in significant conductivity; however, the maximum conductivity of 0.27 S/m is observed with the widest tunnels (d = 40 nm) and the highest CNF aspect ratio of 1000.

Background: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. Methods: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. Results: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07–1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28–0.67; p

Abstract Numerous challenges, like the uninterrupted supply of electricity, stable and reliable power, and energy storage during non‐operational hours, arise across various industries due to the absence of advanced energy storage technologies. With the continual technological advancements in portable electronics, green energy, and transportation, there are inherent limitations in their innovative production. Thus, ongoing research is focused on pursuing sustainable energy storage technologies. An emerging solution lies in the development of asymmetric supercapacitors (ASCs), which offer the potential to extend their operational voltage limit beyond the thermodynamic breakdown voltage range of electrolytes. This is achieved by employing two distinct electrode materials, presenting an effective solution to the energy storage limitations faced by ASCs. The current review concentrates on the progression of working materials to develop authentic pseudocapacitive energy storage systems (ESS). Also, evaluates their ability to exceed energy storage constraints. It provides insights into fundamental energy storage mechanisms, performance evaluation methodologies, and recent advancements in electrode material strategies. The review approaches developing high‐performance electrode materials and achieving efficient ASC types. It delves into critical aspects for enhancing the energy density of ASCs, presenting debates and prospects, thereby offering a comprehensive understanding and design principles for next‐generation ASCs in diverse applications.

Abstract Establishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, combining excellent electrical conductivity, high breakdown voltage, solution processability, and two-dimensional morphology, are promising candidates for contacts in microelectronics. However, their hydrophilic surfaces, which enable spontaneous environmental degradation and poor dispersion stability in organic solvents, have restricted certain electronic applications. Herein, electrohydrodynamic printing technique is used to fabricate fully solution-processed thin-film transistors with alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2T x (AD-MXene) as source, drain, and gate electrodes. The AD-MXene has excellent dispersion stability in ethanol, which is required for electrohydrodynamic printing, and maintains high electrical conductivity. It outperformed conventional vacuum-deposited Au and Al electrodes, providing thin-film transistors with good environmental stability due to its hydrophobicity. Further, thin-film transistors are integrated into logic gates and one-transistor-one-memory cells. This work, unveiling the ligand-functionalized MXenes’ potential in printed electrical contacts, promotes environmentally robust MXene-based electronics (MXetronics).

Highlights Recent progress in Zn–air batteries is critically reviewed. Current challenges of rechargeable Zn–air batteries are highlighted. Strategies for the advancement of the anode, electrolyte, and oxygen catalyst are discussed. Future research directions are provided to design commercial Zn–air batteries.

To achieve carbon neutrality in 2050, Thailand has focused on reducing CO2 emissions in the energy sector. Small modular reactors (SMRs) and renewable energy such as wind and solar represent an interesting alternative for the decarbonization of the energy sector. This study aims to investigate the possibility of establishing a grid-connected hybrid energy system (Grid/Solar PV/Wind Turbine/BESS/SMRs) to fulfill the energy demand of Phuket Island in Thailand and to minimize net present cost (NPC), levelized cost of energy (LCOE), and greenhouse gas (CO2) emissions. A grid-connected hybrid renewable generation system was simulated using HOMER. Four combinations of grid-connected and renewable energy sources were developed based on the electricity demand and renewable resources available at the site. The simulation results indicate that the most optimal scenario is the Grid/PV/WT/SMR system, which offers a 28% reduction in NPC and LCOE compared to the grid-only system and reduces CO2 emissions by over 58% compared to the total emissions from the utility grid. The simulation results demonstrate that the grid-connected and hybrid energy system is the most viable option to meet electricity demand and reduce greenhouse gas emissions on Phuket Island.

Abstract Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer’s disease (AD), also known as “type 3 diabetes”. Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, β-amyloid oligomers, plaques, phosphorylated tau, and GSK3β expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.

Refractory chylous ascites can cause significant nutritional and immunologic morbidity, but no clear treatment has been established. This article introduces a case of a 22-year-old female patient with an underlying lymphatic anomaly who presented with refractory chylous ascites after laparoscopic adnexectomy for ovarian teratoma which aggravated after thoracic duct embolization. Ascites (>3,000 mL/d) had to be drained via a percutaneous catheter to relieve abdominal distention and consequent dyspnea, leading to significant cachexia and weight loss. Two sessions of hybrid lymphovenous anastomosis (LVA) surgery with intraoperative mesenteric lymphangiography guidance were performed to decompress the lymphatics. The first LVA was done between inferior mesenteric vein and left para-aortic enlarged lymphatics in a side-to-side manner. The daily drainage of chylous ascites significantly decreased to 130 mL/day immediately following surgery but increased 6 days later. An additional LVA was performed between right ovarian vein and enlarged lymphatics in aortocaval area in side-to-side and end-to-side manner. The chylous ascites resolved subsequently without any complications, and the patient was discharged after 2 weeks. The patient regained weight without ascites recurrence after 22 months of follow-up. This case shares a successful experience of treating refractory chylous ascites with lymphatic anomaly through LVA, reversing the patient's life-threatening weight loss. LVA was applied with a multidisciplinary approach using intraoperative mesenteric lipiodol, and results showed the possibility of expanding its use to challenging problems in the intraperitoneal cavity.

This study investigates resource adequacy and renewable energy integration in the United States, European Union, and Pakistan amid global energy market liberalization and greenhouse gas reduction efforts. It explores how these regions are adapting to the surge in renewable sources like wind and solar, which, despite their financial and environmental benefits, challenge resource adequacy and the economic viability of traditional energy sources. In the US and EU, significant improvements have been introduced in wholesale electricity markets and capacity accreditation mechanisms, which enhanced the large-scale deployment of renewables. This shift has prompted a reevaluation of resource adequacy, leading to the increased deployment of battery storage and demand response. Presently, gas-based generation is largely upholding resource adequacy; however, future trends indicate a move towards greater consumer participation, energy efficiency, and utility-scale storage, with a decline in fossil fuel use. Pakistan aims to adopt a liberalized market structure by balancing competitive markets with legacy contracts. Public pressure is driving a shift from costly fossil-based generation to renewables. Similarly, a trend in the rise of behind-the-meter solar generation can be witnessed. In the future, Pakistan may also experience resource adequacy challenges. It will likely need to implement battery storage, demand response, and modern capacity accreditation tools, by drawing lessons from developed markets.

Al-Si alloys are vital in the aerospace and automotive industries due to their high strength-to-weight ratio, excellent ductility, and superior corrosion resistance. These properties, along with good thermal conductivity, low thermal expansion, and enhanced wear resistance due to silicon, make them ideal for lightweight, high-performance components like engine parts exposed to harsh conditions and thermal cycling. In recent years, the development of aluminium metal matrix composites using Al-Si alloys as the base material has gathered significant attention. These composites are engineered by integrating various reinforcing particles into the aluminium matrix, which results in remarkable improvements in the wear resistance, hardness, and overall mechanical performance of the material. The stir casting process, a well-established and cost-effective method, is frequently employed to ensure a uniform distribution of these reinforcing particles within the matrix. This review delves into the influence of different types of reinforcing particles on the properties of Al-Si alloy-based AMCs. The incorporation of these reinforcements has been shown to significantly enhance wear resistance, reduce friction, and improve the overall strength and toughness of the composites, making them ideal candidates for high-performance applications in the automotive and aerospace sectors. Moreover, this review highlights the challenges associated with the fabrication of these composites, such as achieving a homogeneous particle distribution and minimizing porosity. It also discusses the latest advancements in processing techniques aimed at overcoming these challenges. Additionally, this review addresses the potential environmental and economic benefits of using natural reinforcements, which not only reduce material costs but also contribute to sustainable manufacturing practices.

Abstract Objective To identify the risk factors for failure of first‐line poly (ADP‐ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer. Method Patients with stage III‐IV epithelial ovarian cancer who received first‐line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups—recur/progression of disease (PD) and non‐recur/PD. Results In total, 191 patients were included. Median follow‐up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non‐high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox‐regression analysis revealed pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03–4.57; p = 0.042), non‐HGSC (3.28; 1.20–8.97; p = 0.021), NAC (2.11; 1.04–4.26; p = 0.037), and no BRCA mutation (2.23; 1.12–4.44; p = 0.023) as independent risk factors associated with poor progression‐free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre‐PARPi serum CA‐125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03–7.39; p = 0.044). Non‐HGSC (5.05; 1.80–14.18; p = 0.002) and NAC (3.36; 1.25–9.04; p = 0.016) were independent risk factors in women without BRCA mutations. Conclusion High pre‐PARPi serum CA‐125 levels, non‐HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first‐line PARPi maintenance therapy. In women with BRCA mutations, high pre‐PARPi serum CA‐125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.

IntroductionWe evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery.MethodsWe prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3).ResultsA total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 – 0.790 and 1.061 – 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS.ConclusionHigh-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.

Background: This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. Methods: All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. Results: Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48–5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. Conclusions: Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.

Highlights This review discusses the roles of MXenes in different positions/layers in perovskite solar cells. The issues in different layers/interfaces and their addressal with the incorporations of MXenes in perovskite solar cells are elaborately discussed.

Organic solar cells (OSCs) have emerged as a promising alternative to traditional inorganic solar cells due to their environmentally friendly nature and inexhaustible solar energy potential. Recent advancements in non-fullerene acceptors (NFAs), particularly the novel NFA Y6 with an acceptor-donor-acceptor (A-D-A) type structure, have significantly boosted the power conversion efficiency (PCE) of OSCs, surpassing 18%. The Y6-based OSCs have demonstrated high open circuit voltage (VOC), short circuit current density (JSC), and fill factor (FF), marking an important milestone in OSC progress. This review focusses exclusively on Y6-based OSCs and their potential to revolutionize the field. It discusses the design strategies and structure-performance relationship for efficient donor materials, with emphasis on polymeric and small molecule donors (SMD). The review highlights the challenges and opportunities in achieving further efficiency improvements beyond 20% for polymeric donors and 16% for small molecules. By leveraging the unique properties of Y6-type acceptors, such as stronger light absorption and tunable energy levels, researchers have achieved remarkable progress in OSC performance. The rational molecular optimization of polymer donors, complementing Y6's narrow bandgap with wide bandgap polymers, and achieving sufficient driving force for charge separation through lower highest-occupied molecular orbital (HOMO) levels, have contributed to the significant PCE enhancements. While Y6-based OSCs have demonstrated great potential, this review also discusses the use of SMD as an increasingly attractive option, offering advantages such as convenient material synthesis and improved crystallinity for higher VOC. Overall, this comprehensive review presents the most advanced developments and insights, paving the way for further advancements in Y6-based OSC technology.

Abstract Stealth technology is used to enhance the survival of military equipment in the field of military surveillance, as it utilizes a combination of techniques to render itself undetectable by enemy radar systems. Radar absorbing materials (RAMs) are specialized materials used to reduce the reflection (or absorption) of radar signals to provide stealth capability, which is a core component of passive countermeasures in military applications. The properties of RAMs can be optimized by adjusting their composition, microstructure, and surface geometry. Carbon‐based materials present a promising approach for the fabrication of ultrathin, versatile, and high‐performance RAMs due to their large specific surface area, lightweight, excellent dielectric properties, high electrical conductivity, and stability under harsh conditions. This review begins with a brief history of stealth technology and an introduction to electromagnetic waves, radar systems, and radar absorbing materials. This is followed by a discussion of recent research progress in carbon‐based RAMs, including carbon blacks, carbon fibers, carbon nanotubes, graphite, graphene, and MXene, along with an in‐depth examination of the principles and strategies on electromagnetic attenuation characteristics. Hope this review will offer fresh perspectives on the design and fabrication of carbon‐based RAMs, thereby fostering a deeper fundamental understanding and promoting practical applications.

Abstract The efficient conductivity of graphene-polymer systems is expressed supposing graphene, tunneling and interphase components. The volume shares and inherent resistances of the mentioned components are used to define the efficient conductivity. Besides, the percolation start and the share of graphene and interphase pieces in the nets are formulated by simple equations. Also, the resistances of tunneling and interphase parts are correlated to graphene conductivity and their specifications. Suitable arrangements among experimented data and model’s estimates as well as the proper trends between efficient conductivity and model’s parameters validate the correctness of the novel model. The calculations disclose that the efficient conductivity improves by low percolation level, dense interphase, short tunnel, large tunneling pieces and poor polymer tunnel resistivity. Furthermore, only the tunneling resistance can govern the electron transportation between nanosheets and efficient conductivity, while the big amounts of graphene and interphase conductivity cannot play a role in the efficient conductivity.

Abstract Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO2) is scarce. Herein, we investigate the associations between prenatal SO2 exposure and ADHD rating scale (ARS) at ages 4, 6 and 8 years repeatedly in a mother–child cohort (n = 329). Whole blood samples were obtained at ages 2 and 6 years, and genome-wide DNA methylation (DNAm) was analyzed for 51 children using the Illumina Infinium HumanMethylation BeadChip. We analyzed the associations between prenatal SO2 exposure and DNAm levels at ages 2 and 6, and further investigated the association between the DNAm and ARS at ages 4, 6 and 8. Prenatal SO2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO2 exposure levels. Of the 6 CpGs, cg07583420 (INS-IGF2) was persistently linked with ARS at ages 4, 6 and 8. Epigenome-wide analysis showed that DNAm at 6733 CpG sites were associated with prenatal SO2 exposure, of which 58 CpGs involved in Notch signalling pathway were further associated with ARS at age 4, 6 and 8 years, persistently. DNAm at age 6 was not associated with prenatal SO2 exposure. Changes in DNAm levels associated with prenatal SO2 exposure during early childhood are associated with increases in ARS in later childhood.

Abstract Background Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. Methods Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. Results Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. Conclusions We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.

Abstract This work presents a power equation for the conductivity of graphene-based polymer composites by the tunneling length, interphase deepness and filler size. The impressions of these factors on the effective concentration and percolation beginning of graphene nano-sheets in nanocomposites are also expressed. The developed equations for percolation beginning and conductivity are examined by the experimented data of some examples, which can guesstimate the interphase depth, tunneling size and percolation exponent. Besides, the impacts of numerous factors on the percolation beginning and conductivity are designed. The developed equation for percolation beginning shows the formation of thick interphase and large tunnels in the reported samples. So, disregarding of tunneling and interphase spaces in polymer graphene nanocomposites overpredicts the percolation beginning. Additionally, the developed model presents the acceptable calculations for the conductivity of samples. Among the mentioned parameters, the concentration and graphene conductivity in addition to the interphase depth induce the strongest effects on the conductivity of composites.

Abstract Background Acute aortic regurgitation (AR) is uncommon condition and usually results in an emergent situation because the left ventricle does not adapt quickly due to a sudden increase in end-diastolic volume caused by the regurgitant flow. Thoracic endovascular aortic repair (TEVAR) is a procedure that places a stent-graft on the lesion of thoracic aorta through a minimally invasive approach. Case presentation Here we report that a catheter-induced aortic valve injury associated with TEVAR can cause delayed AR, exemplified by the case of a patient who developed acute AR 42 months after TEVAR. For this, aortic valve replacement was performed and the patient was discharged without complications. Conclusion Our results demonstrate that when a catheter-related procedure is performed around the aortic valve, slight injury of the valve can cause aortic insufficiency even 3 years after surgery. Consequently, when performing a catheter-related procedure around the aortic valve, special attention is always required.

IntroductionTo evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM).MethodsWe retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into

Abstract Epoxy-based nanocomposites can be ideal electromagnetic interference (EMI)-shielding materials owing to their lightness, chemical inertness, and mechanical durability. However, poor conductivity and brittleness of the epoxy resin are challenges for fast-growing portable and flexible EMI-shielding applications, such as smart wristband, medical cloth, aerospace, and military equipment. In this study, we explored hybrid nanofillers of single-walled carbon nanotubes (SWCNT)/reduced graphene oxide (rGO) as conductive inks and polyester fabrics (PFs) as a substrate for flexible EMI-shielding composites. The highest electrical conductivity and fracture toughness of the SWCNT/rGO/PF/epoxy composites were 30.2 S m−1 and 38.5 MPa m1/2, which are ~ 270 and 65% enhancement over those of the composites without SWCNTs, respectively. Excellent mechanical durability was demonstrated by stable electrical conductivity retention during 1000 cycles of bending test. An EMI-shielding effectiveness of ~ 41 dB in the X-band frequency of 8.2–12.4 GHz with a thickness of 0.6 mm was obtained with an EM absorption-dominant behavior over a 0.7 absorption coefficient. These results are attributed to the hierarchical architecture of the macroscale PF skeleton and nanoscale SWCNT/rGO networks, leading to superior EMI-shielding performance. We believe that this approach provides highly flexible and robust EMI-shielding composites for next-generation wearable electronic devices.

Objective This study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract. Methods We prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated. Results A total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300–22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0–8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively. Conclusion LEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.

Abstract Background A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to establishing innovative chemotherapeutical and surgical strategies without any limitation on rodent models. Methods A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with laparoscopic surgery. In phase I trial, 5.0 × 106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0 × 106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns within the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to 4 weeks after inoculation. Tumor tissues disseminated in the peritoneum 4 weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining. Results In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at 3 weeks after the first inoculation, which increased to 14 and 15 after 4 weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at 4 weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Immunohistochemical H&E and PAX-8 staining confirmed metastatic tumors. Conclusions This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cell lines from humans. Using two cell lines, the PM rate is 75%.

Abstract Background This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). Methods Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. Results Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18–9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2–185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3–109.0] vs. 129.5 months [95% CI, 114.1–144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3–142.3] vs. 115.7 months [95% CI, 96.0–135.4]; P = 0.928). Conclusions This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-β-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-β signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.

The skin sensitization potential of agrochemicals can be assessed using laboratory methods such as the keratinocyte activation assay so that their use in regulatory toxicology might replace experimental animal testing. Here, we evaluated the skin sensitization potential of 11 agrochemicals by using an antioxidant response element–nuclear factor erythroid 2 luciferase assay in KeratinoSens and LuSens cells and applying a skin sensitization adverse outcome pathway (AOP). The KeratinoSens and LuSens assays consistently evaluated the skin sensitization potential of 10/11 agrochemicals with reference to animal testing databases. Benomyl, pretilachlor, fluazinam, terbufos, butachlor, and carbosulfan were correctly detected as sensitizers, and glufosinate ammonium, oxiadiazon, tebuconazole, and etofenprox were correctly detected as non-sensitizers. For diazinon, the skin sensitizing potential was positive in the KeratinoSens assay but not in the LuSens assay. These results suggest that the evaluation of in vitro skin sensitization using the AOP mechanism can be applied to assess active agrochemicals.

Abstract Background The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. Methods This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. Discussion We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. Trial registration ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

Abstract Background PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. Methods Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. Discussion PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. Trial registration ClinicalTrials.gov Identifier: NCT04678102 .

Objective: This study aimed to identify the impact of care and change in the consultation process given by a gynecologic hospitalist on patient waiting time in the emergency department (ED). Materials and methods: This is a pre-post study that compared patients’ length of stay at the ED ten months before and after intervention by the gynecologic hospitalist in 2018. The consultation process changed from ED staff contacting the gynecologic resident (pre-intervention group) to directly contacting the gynecologic hospitalist (post-intervention group). Times elapsed from gynecologic consultation to final disposition, from gynecologic consultation to discharge, and from arrival at ED to discharge were compared between the two groups. Results: Among 945 referrals at the ED during the study period, the number of daytime weekday gynecologic consultations were 68 and 187 cases in the pre-intervention and post-intervention groups, respectively. The time elapsed from gynecologic consultation to the final disposition, the time elapsed from gynecologic consultation to discharge and the time elapsed from arrival at ED to discharge were shorter in the post-intervention group than in the pre-intervention group (median values, 98 vs. 167.5 min, 205 vs. 311.5 min, and 419 vs. 497 min; P

Objective The three major gynecologic cancers are cervical, endometrial, and ovarian cancer. This study aimed to describe the 19-year trends and survival rates in cervical, endometrial, and ovarian cancer in a Korean female population. Methods We searched the Korea Central Cancer Registry to identify patients with gynecologic cancer between 1999 and 2017. Age-standardized rates and annual percent changes were calculated. The relative survival rate (RSR) was reported by histology, age, and stage for each gynecological cancer. Results The total number of cervical, endometrial, primary peritoneal, ovarian epithelial, fallopian tube (POFT) cancer was 134,863, with the number of cases increasing every year: 6,077 in 1999 to 8,011 in 2017. The incidence of cervical cancer has decreased; however, that of POFT and endometrial cancer has increased. The 5-year RSR of cervical, POFT, and endometrial cancer was reported to be 80.8%, 61.4%, and 88.1%, respectively. In the case of cervical cancer, squamous cell carcinoma showed better survival than other histology (82.8% vs. 73.5%). Furthermore, in the case of endometrial cancer, endometrioid histology had substantially better 5-year RSR than the others (93.2% vs. 76.5%). Contrastingly, in the case of ovarian cancer, serous carcinoma had worse 5-year RSR than other types of histology. Conclusion The incidence rates for gynecologic cancers increased from 2005 to 2017, with an annual increase of 2.76 per year until 2017. Endometrial cancer had the highest RSR, while ovarian cancer had the lowest. Active cancer screening and the introduction of effective treatments might have contributed to the improved RSRs of gynecologic cancers.

Introduction Even though the injection of diluted vasopressin into the uterus is expected to reduce intraoperative bleeding with decreased adverse effects during robot-assisted laparoscopic myomectomy (RALM), there is a lack of relevant trials to show its effect and safety. Thus, this study was designed to compare the effect and safety of vasopressin injection on bleedings based on dilution levels of vasopressin with constant volumes during RALM.Methods and analysis This is a randomised controlled pilot trial, where a total of 39 patients will be randomly divided into three experimental groups in a 1:1:1 ratio. All patients will be classified into the three groups based on the dilution level of vasopressin: group 1—a solution prepared by mixing 20 units of vasopressin with 100 mL of normal saline to make a total of 100 mL; group 2—a solution prepared by mixing 20 units of vasopressin with 200 mL of normal saline to make a total of 100 mL and group 3—a solution prepared by mixing 20 units of vasopressin with 400 mL of normal saline to make a total of 100 mL. During RALM, we will inject diluted vasopressin at different concentrations with a total of 100 mL. As the primary endpoint, estimated blood loss would be compared. As secondary endpoints, we will check the level of haemoglobin and haematocrit, operation time, amount of transfusion, and the period of hospitalisation. In addition, we will check other complications related to vasopressin injection.Ethics and dissemination This pilot study has been approved by the Institutional Review Board of the Seoul National University Hospital (No. H-2011-107-1174). All potential subjects will be provided written informed consent. The results of this study will be published in peer-reviewed journals and be presented at academic conferences.Trial registration numbers NCT04874246 and CKCT0006225.

Least cost paths (LCPs) have been widely used by archaeologists and geographers to reconstruct probable routes of movement within past landscapes using GIS-based modelling. By definition, LCP modelling is based on the premise that ‘least cost’ features as the primary factor in the decision-making of movement. It can be argued, however, that movement within the landscape was structured not only by the need to 'minimize costs' but also by the desire to 'maximize benefits'. This study introduces a new way of estimating terrain costs that can factor in this tendency towards ‘benefit maximization’ when modelling routes. This alternative methodology features a distinctive way of perceiving the landscape, which differs from the grid-based division of the landscape generally used in LCP modelling. The landscape is seen to be made up of ten different ‘hillslope position units’ (which are generic landscape units widely used in landscape evolution studies) and ‘movement suitability’ values are estimated for each of the hillslope position units. These values are then used to produce a ‘hillslope position unit movement suitability’ (HPMS) cost surface. The evaluation of the HPMS cost surface is undertaken by comparing HPMS-based routes and slope gradient-based LCPs against the historical roads of Korea’s Joseon Dynasty (1392–1910). It is observed that HPMS-based routes demonstrate a greater degree of correspondence with historically confirmed routes, compared to slope gradient-based LCPs. The similarity between HPMS-based routes and historically confirmed routes is found to be greater in mountainous regions 'vis-à-vis' non-mountainous regions. It is proposed that, by taking into account human desire to utilize beneficial landscapes, HPMS-based cost surfaces may result in modelled routes that are closer to actual past experiences.

Abstract Background Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local inflammation and pelvic adhesion. The prevalence of EMS is about 10% in reproductive-age women and higher in women with pelvic pain or infertility. For young patients with ovarian EMS, laparoscopic ovarian cystectomy is effective in relieving pelvic pain and preventing local recurrence. However, there is a concern that the ovarian reserve would decrease after the operation because of the removal of a part of the normal ovarian tissue and thermal damage during hemostasis, which depends on the types of hemostasis such as bipolar electrocoagulation, suturing, and the use of a hemostatic agent. In this study, we aim to evaluate the protective effect for the ovarian reserve and hemostasis between a hemostatic agent and suturing during laparoscopic ovarian cystectomy for patients with ovarian EMS. Methods This study is a randomized controlled, non-inferiority trial, where a total of 90 patients with ovarian EMS will be randomly assigned to the experimental (hemostatic agent) and control (suturing) groups. In the control group, a barbed suture will be applied for hemostasis, whereas a hemostatic agent will be applied in the experimental group. If two methods are insufficient, bipolar electrocoagulation will be applied for complete hemostasis. As the primary endpoint, the reduction rate of serum anti- Müllerian hormone (AMH) levels reflecting the ovarian reserve will be compared between the two groups 12 weeks after surgery. As secondary endpoints, we will compare the reduction rate of AMH level 48 weeks after surgery, the time required to complete hemostasis, the success rate of hemostasis within 10 min, and adverse events associated with operation. Discussion We expect that the protective effect for the ovarian reserve and hemostasis may be comparable between the two methods, suggesting that a hemostatic agent may be preferred considering that it is easy to use during laparoscopic ovarian cystectomy. Trial registration ClinicalTrials.gov NCT04643106 . Registered on 22 November 2020

Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.

Background: The complete contact tracing of coronavirus disease-19 (COVID-19) cases in South Korea allows a unique opportunity to investigate cluster characteristics. This study aimed to investigate all reported COVID-19 clusters in the Seoul metropolitan area from January 23 to September 24, 2020. Methods: Publicly available COVID-19 data was collected from the Seoul Metropolitan City and Gyeonggi Province. Community clusters with ≥5 cases were characterized by size and duration, categorized using K-means clustering, and the correlation between the types of clusters and the level of social distancing investigated. Results: A total of 134 clusters comprised of 4033 cases were identified. The clusters were categorized into small (type I and II), medium (type III), and large (type IV) clusters. A comparable number of daily reported cases in different time periods were composed of different types of clusters. Increased social distancing was related to a shift from large to small-sized clusters. Conclusions: Classification of clusters may provide opportunities to understand the pattern of COVID-19 outbreaks better and implement more effective suppression strategies. Social distancing administered by the government may effectively suppress large clusters but may not effectively control small and sporadic clusters.

Alpinumisoflavone is an isoflavonoid extracted from the Cudrania tricuspidate fruit and Genista pichisermolliana. It has various physiological functions, such as anti-inflammation, anti-proliferation, and apoptosis, in malignant tumors. However, the effect of alpinumisoflavone is still not known in chronic diseases and other benign reproductive diseases, such as endometriosis. In this study, we examined the cell death effects of alpinumisoflavone on the endometriosis cell lines, End1/E6E7 and VK2/E6E7. Results indicated that alpinumisoflavone inhibited cell migration and proliferation and led to cell cycle arrest, depolarization of mitochondria membrane potential, apoptosis, and disruption of calcium homeostasis in the endometriosis cell lines. However, the cellular proliferation of normal uterine epithelial cells was not changed by alpinumisoflavone. The alteration in Ca2+ levels was estimated in fluo-4 AM-stained End1/E6E7 and VK2/E6E7 cells after alpinumisoflavone treatment with or without calcium inhibitor, 2-aminoethoxydiphenyl borate (2-APB). The results indicated that a combination of alpinumisoflavone and a calcium inhibitor reduced the calcium accumulation in the cytosol of endometriosis cells. Additionally, alpinumisoflavone decreased oxidative phosphorylation (OXPHOS) in the endometriotic cells. Moreover, protein expression analysis revealed that alpinumisoflavone inactivated AKT signaling pathways, whereas it increased MAPK, ER stress, and autophagy regulatory proteins in End1/E6E7 and VK2/E6E7 cell lines. In summary, our results suggested that alpinumisoflavone could be a promising effective management agent or an adjuvant therapy for benign disease endometriosis.

Abstract The preservation of ovarian reserve during laparoendoscopic single-site (LESS) ovarian cystectomy is crucial for reproductive-age women. This study was a single-blinded, single-center, and randomized controlled trial to evaluate the effect of hemostatic agents on the preservation of ovarian reserve and hemostasis during LESS ovarian cystectomy. Patients with unilateral ovarian cyst were randomized to the hemostatic agent and coagulation groups according to the hemostasis method. Afterwards, the patients underwent LESS ovarian cystectomy, and hemostasis was performed after ovarian cyst excision according to the assigned hemostasis method. If hemostasis was not completed within 10 min. After discharge, the patients were followed until 3 months after surgery. We compared the hemoglobin, anti-Müllerian hormone (AMH) levels, and ovarian volumes before surgery, and 2 days, 1 week, and 3 months after surgery (3 M-POST), and the decline ratio between the two groups. The decline ratio of serum AMH levels was greater at 3 M-POST in the coagulation than in the hemostatic agent group (median intention-to-treat [ITT], − 36.7 vs. − 13.3%; per-protocol [PP], − 36.8 vs. − 13.3%; P

This study aims to evaluate the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Because relevant medical devices have not been introduced, we developed our prototype of pressurized intraperitoneal aerosol chemotherapy (PIPAC) and RIPAC by adding a conical pendulum motion device for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate the drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate the tissue concentrations and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle, DreamPen® (Dalim Biotech, Gangwon, South Korea), with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 min. As a result, RIPAC showed a wider distribution and stronger intensity than PIPAC. Compared with PIPAC, RIPAC demonstrated high values of the tissue concentration in the central, right upper, epigastrium, left upper, left lower, right lower, and right flank regions (median, 375.5–2124.9 vs. 161.7–1240 ng/ml; p ≤ .05), and higher values of the depth of concentrated diffusion and depth of maximal diffusion (median, 232.5–392.7 vs. 116.9–240.1 μm; 291.2–551.2 vs. 250.5–362.4 μm; p ≤ .05) in all regions except for bowels. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no related toxicities. Conclusively, RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.