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Purpose To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR. Methods A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates. Results The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach. Conclusion The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

Introduction: Despite the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), most patients with non-small-cell lung cancer (NSCLC) eventually develop resistance to these agents. Notably, EGFR _C797S mutations confer resistance to the third-generation EGFR-TKI osimertinib and no approved post-osimertinib targeted pharmacology options are currently available. BLU-945 is a novel, reversible, and orally available next-generation EGFR-TKI that selectively targets EGFR-activating ( EGFR m) and resistance mutations (including EGFR_C797S) with nanomolar potency while sparing wild-type EGFR in vitro. Methods: In vitro activity of BLU-945 as a single agent and in combination with osimertinib was tested in engineered EGFR -mutant cell lines as well as patient-derived cells and patient-derived organoids. In vivo activity was evaluated in osimertinib-resistant patient-derived xenograft mouse models. Three patient cases from the global, first-in-human, phase I/II SYMPHONY trial (NCT04862780) demonstrating the clinical efficacy of BLU-945 were reported. Results: In vitro BLU-945 demonstrated inhibited cell viability and growth of EGFR -mutant/osimertinib-resistant cell lines. BLU-945 demonstrated in vivo tumor shrinkage in osimertinib-resistant models of NSCLC (osimertinib second line: EGFR _L858R/C797S and third line: EGFR _ex19del/T790M/C797S and L858R/T790M/C797S) both as monotherapy and in combination with osimertinib. BLU-945 also demonstrated tumor shrinkage in patients from the SYMPHONY trial. Conclusion: Our findings demonstrate the preclinical and early clinical activity of BLU-945 in EGFR m NSCLC progressing on previous EGFR-TKIs.

Ponatinib is a potent tyrosine kinase inhibitor that is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. To further expand its clinical applications, accurate quantification of ponatinib in plasma is essential. In this study, we developed and validated a sensitive and selective high-performance liquid chromatography (HPLC) method coupled with a fluorescence detector (FLD) to measure ponatinib concentrations in rat plasma using the Analytical Quality by Design approach. Briefly, we screened and optimized the critical method parameters using the Taguchi and Box-Behnken designs. The developed method had excellent linearity in the range of 1–1000 ng/mL, sensitivity, and reproducibility, and required minimal sample volume and a short run time. Compared with previously reported HPLC-ultraviolet (UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, this HPLC-FLD method offers superior sensitivity, simpler sample preparation, and greater efficiency. We successfully used this method in a pharmacokinetic study in rats to obtain reliable data on ponatinib plasma concentrations. Altogether, this analytical method will be applicable in several analytical conditions and will support further pharmacokinetic and clinical investigations of ponatinib for various cancer treatments.

Cardiovascular disease remains a global health concern. Stem cell therapy utilizing human cardiac progenitor cells (hCPCs) shows promise in treating cardiac vascular disease. However, limited availability and senescence of hCPCs hinder their widespread use. To address these challenges, researchers are exploring innovative approaches. In this study, a bioengineered cell culture plate was developed to mimic the natural cardiac tissue microenvironment. It was coated with a combination of extracellular matrix (ECM) peptide motifs and mussel adhesive protein (MAP). The selected ECM peptide motifs, derived from fibronectin and vitronectin, play crucial roles in hCPCs. Results revealed that the Fibro-P and Vitro-P coated plates significantly improved hCPC adhesion, proliferation, migration, and differentiation compared to uncoated plates. Additionally, long-term culture on the coated plates delayed cellular senescence and maintained hCPC stemness. These enhancements were attributed to the activation of integrin downstream signaling pathways. The findings suggest that the engineered ECM peptide motif-MAP-coated plates hold potential for enhancing the therapeutic efficacy of stem cell-based therapies in cardiac tissue engineering and regenerative medicine.

Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder. Unlike urothelial carcinoma, which accounts for most bladder cancers, it occurs in the submucosal portion of the bladder wall and consists of the lamina propria, muscularis propria, and adventitia. It is presumed to originate from poorly differentiated pluripotent mesenchymal cells in which fibroblasts and histiocytes are partially differentiated. Radiologically, it is known as the “non-papillary tumor” and is commonly diagnosed as a large mass without necrosis, which shows invasion beyond the muscularis propia. Although the prognosis of this rare malignancy depends on pathological parameters, it generally has a poor prognosis with high local tumor recurrence. Here, we present a case of primary MFH in the urinary bladder with clinical symptoms of lower abdominal pain without gross hematuria that recurred rapidly and showed an aggressive disease course.

Abstract Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer’s disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics.

Abstract Background Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). Methods We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges’ g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. Results A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. Conclusion This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. Trial registration PROSPERO CRD42022384024

Abstract Background Atlantodental subluxation (ADS) is a serious condition that can result in sudden death. Measuring the anterior atlantodental interval (AADI method) is the gold standard for diagnosis but the complex anatomy of this region can make diagnosis difficult, especially for beginners. Therefore, we would like to use a simpler method, the Swischuk line method, to diagnose ADS. The purpose of our study was to evaluate the diagnostic performance of the Swischuk line method for ADS on lateral cervical spine radiographs compared to the AADI method. Methods A retrospective study was conducted with patients who presented with ADS (ADS group, n = 32, mean age 57.78 years, age range 34–82 years, 10 men, 21 women) and an age- and sex-matched control group (n = 32). The diagnostic performance of the AADI method and the Swischuk line method for ADS was assessed using lateral cervical radiographs in both flexion and neutral postures by an experienced musculoskeletal radiologist (reader 1), a senior resident (reader 2), and a junior resident (reader 3) in the radiologic department. Results In the flexion posture, the AADI method and the Swischuk line method showed excellent diagnostic performance with AUCs > 0.9 for readers 1 2 and reader 3. In a neutral posture, the diagnostic performance of the AADI and Swischuk line methods was decreased. With a 1 mm cut-off value using the Swischuk line method in flexion posture, the sensitivity was 75% or more, the specificity was 100%, and the accuracy was 87.50% or more 90.63% for all readers. With a 2 mm cut-off value, the sensitivity was low (37.50-46.88%) but the specificity was 100% for all three readers. In a neutral posture, the sensitivity for both methods decreased, though specificity remained high (> 80%). Conclusions The Swischuk line method was found to be reliable and showed high sensitivity and specificity with a cut-off value of 1 mm for the diagnosis of ADS in cervical lateral radiographs in flexion posture. It can be used as a complement to the AADI method.

Abstract The molecular changes that occur with the progression of Alzheimer’s disease (AD) are well known, but an understanding of the spatiotemporal heterogeneity of changes in the brain is lacking. Here, we investigated the spatially resolved transcriptome in a 5XFAD AD model at different ages to understand regional changes at the molecular level. Spatially resolved transcriptomic data were obtained from 5XFAD AD models and age-matched control mice. Differentially expressed genes were identified using spots clustered by anatomical structures. Gene signatures of activation of microglia and astrocytes were calculated and mapped on the spatially resolved transcriptomic data. We identified early alterations in the white matter (WM) of the AD model before the definite accumulation of amyloid plaques in the gray matter (GM). Changes in the early stage of the disease involved primarily glial cell activation in the WM, whereas the changes in the later stage of pathology were prominent in the GM. We confirmed that disease-associated microglia (DAM) and astrocyte (DAA) signatures also showed initial changes in WM and that activation spreads to GM. Trajectory inference using microglial gene sets revealed the subdivision of DAMs with different spatial patterns. Taken together, these results help to understand the spatiotemporal changes associated with reactive glial cells as a major pathophysiological characteristic of AD. The heterogeneous spatial molecular changes apply to identifying diagnostic and therapeutic targets caused by amyloid accumulation in AD.

ABSTRACTUnripe apples contain more functional compounds than ripe apples and thus demonstrate significant potential for use as functional food materials. In this study, the conditions for the extraction of functional compounds from unripe apples were optimized using the response surface methodology. A Box–Behnken design was used to investigate the effects of three independent variables (β-cyclodextrin concentration, extraction time, and extraction temperature) on the total polyphenol content (TPC), chlorogenic acid content (CAC), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (RSA). The corresponding optimal extraction conditions were found to be 40 mg/mL, 53.03 min, and 60°C for TPC; 40 mg/mL, 46.67 min, and 60°C for CAC; and 20 mg/mL, 30 min, and 40°C for DPPH RSA. The experimental values obtained under these conditions were consistent with the predicted values, indicating that the model was suitable for optimizing the extraction of functional compounds from unripe apples.

Background/Objectives: Our research introduces a novel screening method to identify antibodies that can suppress cell proliferation and induce apoptosis. Methods: By using an autocrine signaling system with lentivirus, we developed an antibody screening method based on FACS sorting assays and cell cycle analysis to inhibit tumor growth in vitro. This approach is particularly well suited for studying tumor suppressors. Inducing the G0 phase in tumor cells with specific antibodies may arrest their growth permanently or trigger apoptosis. The cell cycle is composed of tightly regulated phases for cell growth and division, with tumorigenesis or apoptosis occurring when these regulatory mechanisms fail. Results: In our study, we identified RACK1 as a key regulator of cancer cell growth. The H9 antibody against RACK1 selected from a human antibody library effectively suppressed cell proliferation by inhibiting RACK1 function. Conclusions: These findings suggest that RACK1 plays a crucial role in tumor cell cycling and could represent a novel therapeutic target for cancer treatment. Although RACK1 is recognized as a significant target protein in various tumors, no commercial therapeutic agents currently exist. Our results suggest that the H9 antibody could be a promising candidate for the development of novel cancer therapies.

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.

Amniotic fluid mesenchymal stem cells (AF-MSCs), which can be obtained from fetal tissue, reportedly have self-renewal capacity and multi-lineage differentiation potential. The aim of this study was to identify the biological characteristics of AF-MSCs and evaluate their stability and safety in long-term culture. To confirm the biological characteristics of AF-MSCs, morphology, proliferation capacity, karyotype, differentiation capacity, gene expression level, and immunophenotype were analyzed after isolating AF-MSCs from equine amniotic fluid. AF-MSCs were differentiated into adipocytes, chondrocytes, and osteocytes. Immunophenotype analyses revealed expression levels of ≥95% and ≤ 2% of cells for a positive and negative marker, respectively. Analysis of the MSCs relative gene expression levels of AF-MSCs was approximately at least twice that of the control. The endotoxin level was measured to verify the safety of AF-MSCs and was found to be less than the standard value of 0.5 EU/ml. AF-MSCs were cultured for a long time without any evidence of abnormalities in morphology, proliferation ability, and karyotype. These results suggest that amniotic fluid is a competent source for acquiring equine MSCs and that it is valuable as a cell therapy due to its high stability.

Natural killer (NK) cells have recently shown renewed promise as therapeutic cells for use in treating hematologic cancer indications. Despite this promise, NK cell manufacturing workflows remain largely manual, open, and disconnected, and depend on feeders, as well as outdated unit operations or processes, often utilizing research-grade reagents. Successful scale-up of NK cells critically depends on the availability and performance of nutrient-rich expansion media and cryopreservation conditions that are conducive to high cell viability and recovery post-thaw. In this paper we used Cytiva hardware and media to expand the NK92 cell line in a model process that is suitable for GMP and clinical manufacturing of NK cells. We tested a range of cryopreservation factors including cooling rate, a range of DMSO-containing and DMSO-free cryoprotectants, ice nucleation, and cell density. Higher post-thaw recovery was seen in cryobags over cryovials cooled in identical conditions, and cooling rates of 1°C/min or 2°C/min optimal for cryopreservation in DMSO-containing and DMSO-free cryoprotectants respectively. Higher cell densities of 5x107 cells/ml gave higher post-thaw viability than those cryopreserved at either 1x106 or 5x106 cells/ml. This enabled us to automate, close and connect unit operations within the workflow while demonstrating superior expansion and cryopreservation of NK92 cells. Cellular outputs and performance were conducive to clinical dosing regimens, serving as a proof-of-concept for future clinical and commercial manufacturing.

Abstract Myopia is one of the risk factors for glaucoma, making accurate diagnosis of glaucoma in myopic eyes particularly important. However, diagnosis of glaucoma in myopic eyes is challenging due to the frequent associations of distorted optic disc and distorted parapapillary and macular structures. Macular vertical scan has been suggested as a useful tool to detect glaucomatous retinal nerve fiber layer loss even in highly myopic eyes. The present study was performed to develop and validate a deep learning (DL) system to detect glaucoma in myopic eyes using macular vertical optical coherence tomography (OCT) scans and compare its diagnostic power with that of circumpapillary OCT scans. The study included a training set of 1416 eyes, a validation set of 471 eyes, a test set of 471 eyes, and an external test set of 249 eyes. The ability to diagnose glaucoma in eyes with large myopic parapapillary atrophy was greater with the vertical than the circumpapillary OCT scans, with areas under the receiver operating characteristic curves of 0.976 and 0.914, respectively. These findings suggest that DL artificial intelligence based on macular vertical scans may be a promising tool for diagnosis of glaucoma in myopic eyes.

Abstract This observational case series study is conducted to compare the extent of microvasculature impairment in the peripapillary retina and choroid in eyes with primary open-angle glaucoma (POAG), and to investigate the association of the discrepancy between the microvasculature impairments of each layer with the rate of progressive retinal nerve fiber layer (RNFL) thinning. A total of 88 POAG eyes with a localized RNFL defect were enrolled, including 67 eyes with and 21 eyes without choroidal microvasculature dropout (CMvD). Circumferential widths of retinal microvascular impairment (RMvI) and CMvD were measured, and eyes were classified based on the relative width of CMvD to RMvI (CMvD/RMvI ratio). The rate of RNFL thinning was determined by linear regression based on ≥ 5 serial OCT examinations. Thinner global RNFL and worse visual field mean deviation at baseline were associated with a larger circumferential width of the RMvI, whereas the presence of cold extremities, lower mean arterial pressure and thinner juxtapapillary choroid were associated with a larger circumferential width of the CMvD. The rate of global RNFL thinning was faster in eyes with larger relative CMvD width than in eyes with equal CMvD and RMvI widths and in eyes without CMvD (P = 0.001). Lower mean arterial pressure (P = 0.041), larger CMvD width (P = 0.046), larger CMvD/RMvI ratio (P = 0.041), and detection of disc hemorrhage during the follow-up (P = 0.013) were significant factors associated with faster global RNFL thinning. Larger CMvD width relative to RMvI width may be indicative of an increased risk of faster RNFL thinning in POAG with localized RNFL defect. Comparing the microvasculature impairment in individual layers may help predict more rapid glaucoma progression.

A key element for the cost-effective development of cultured meat is a cell line culturable in serum-free conditions to reduce production costs. Heme supplementation in cultured meat mimics the original meat flavor and color. This study introduced a bacterial extract generated from Corynebacterium that was selected for high-heme expression by directed evolution. A normal porcine cell line, PK15, was used to apply the bacterial heme extract as a supplement. Consistent with prior research, we observed the cytotoxicity of PK15 to the heme extract at 10 mM or higher. However, after long-term exposure, PK15 adapted to tolerate up to 40 mM of heme. An RNA-seq analysis of these heme-adapted PK15 cells (PK15H) revealed a set of altered genes, mainly involved in cell proliferation, metabolism, and inflammation. We found that cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), lactoperoxidase (LPO), and glutathione peroxidase 5 (GPX5) were upregulated in the PK15H heme dose dependently. When we reduced serum serially from 2% to serum free, we derived the PK15H subpopulation that was transiently maintained with 5–10 mM heme extract. Altogether, our study reports a porcine cell culturable in high-heme media that can be maintained in serum-free conditions and proposes a marker gene that plays a critical role in this adaptation process.

It is important to distinguish uterine lesions from other lesions occurring in the pelvic cavity for the proper management. The primary radiological evaluation of uterine lesions is performed using transvaginal ultrasonography, and if the lesion is too large or shows atypical benign imaging findings, magnetic resonance imaging should be performed. Analyzing radiological findings of uterine lesions through a pattern recognition approach can help establish the accurate diagnosis and treatment plan. In this pictorial assay, we describe imaging characteristics of various lesions arising from the uterus and evaluate them based on the pattern recognition approach.

Abstract Glaucoma is a multifactorial disease where various systemic features are involved in the progression of the disease. Based on initial systemic profiles in electronic medical records, this study aimed to develop a model predicting factors of long-term rapid retinal nerve fiber layer (RNFL) thinning over 5 years in 505 patients with primary open-angle glaucoma. Eyes with faster or slower RNFL thinning were stratified using a decision tree model, and systemic and ophthalmic data were incorporated into the models based on random forest and permutation methods, with the models interpreted by Shapley additive explanation plots (SHAP). According to the decision tree, a higher lymphocyte ratio (> 34.65%) was the most important systemic variable discriminating faster or slower RNFL thinning. Higher mean corpuscular hemoglobin (> 32.05 pg) and alkaline phosphatase (> 88.0 IU/L) concentrations were distinguishing factors in the eyes with lymphocyte ratios > 34.65% and

To protect people and the environment from environmental radiation, the Act on Protective Action Guidelines against Radiation in the Natural Environment was formulated in Korea in 2011. This law regulates matters related to radiation safety that can be encountered in life. In accordance with this law, radiation monitoring equipment is operated at major airports and ports across the country, ensuring radiation monitoring of imported cargo. Currently, six ministries conduct radiation monitoring of imported cargo: the Nuclear Safety and Security Commission; the Korea Customs Service; the Ministry of Food and Drug Safety; the Ministry of Environment; the Ministry of Agriculture, Food and Rural Affairs; and the Korea Forest Service. Each ministry designates the relevant cargo items for radiation monitoring. The objective of this study was to comprehensively review the Korean radiation monitoring system for imported cargo and identify the areas and scopes of improvement. This paper also proposes a new law and an integrated supervision plan, which involves establishing a dedicated department to enhance the efficiency and professionalism of the national radiation monitoring system for imported cargo. The review will contribute to the development of a more sophisticated national radiation monitoring system for imported cargo.

Abstract Contrast sensitivity (CS) is closely associated with vision-related quality of life in glaucoma patients. This cross-sectional study was performed to determine the relationship between CS and visual field (VF) sensitivity (VFS) according to the hemifield location of VF defects in 238 patients with primary open-angle glaucoma (POAG) who underwent 24-2 standard automated perimetry and CS measurement on the same day. Of the 238 eyes, 83, 58, and 47 eyes had VF defects in the superior, inferior and both hemifields, respectively, and 50 had no VF defects in either hemifield. Significant correlations between CS and VFS in all sectors were observed in the entire cohort (R 2 = 0.103–0.315, all P

Abstract Kori 1, the first commercial reactor in Korea, was permanently shut down in 2017 and is preparing for decommissioning in the mid‐2020s. Although Kori 1 is shut down, some radiation sources remain in the system; as such, the dismantling workers are exposed to radiation until decommissioning is completed. Unexpected radiation events have been reported in some decommissioning nuclear power plants (NPPs), which resulted in additional radiation exposure to workers and significant financial losses due to delays in the decommissioning schedule. Hence, an appropriate radiation protection program must be established to minimize radiation exposure as well as the economic burden. In this study, radiation doses from precedent decommissioning NPPs worldwide are compared with those estimated from Kori 1 to determine dose reduction measures that can achieve radiation exposure as low as reasonably achievable to decommissioning workers.

Endometriosis-related symptoms are believed to be alleviated during pregnancy. However, pregnancy complications, such as pseudoaneurysm of the uterine artery, rupture of ovarian or uterine vessels, and intraabdominal bleeding from decidualized deep infiltrating endometriosis (DIE) lesion have been rarely reported. Owing to the potential risk of rupture and resultant life-threatening complications, proper diagnosis and close monitoring of decidualized endometriotic lesion are very important despite its low relative risk. Till date, massive vaginal bleeding from decidualized rectovaginal DIE during pregnancy has not been in English literatures. Here, we present the first case of spontaneous massive vaginal bleeding due to decidualized rectovaginal DIE that occurred in the late third trimester of pregnancy.

Abstract To investigate the diagnostic value of combined SWE, SMI, and B-mode US scores for distinguishing between benign and malignant masses. A total of 450 breast masses that underwent US-guided core needle biopsies were prospectively enrolled. The breast masses were assessed based on the BI-RADS and quantitative SWE and SMI parameters. The SWEmax, SWEratio, and SMIVI cutoff value were determined using Youden’s index by comparison to the pathological results. The BI-RADS categories were scored on a scale from 1 to 5, and SWEmax, SWEratio, and SMIVI were dichotomized based on each cutoff values (0 or 1). The combined scores (1 to 8) were calculated as the sum of the BI-RADS score and the quantitative scores and compared to the pathologic results using AUROC analysis. The cutoff values were 52.25 kPa for SWEmax, 5.03 for SWEratio, and 2.15% for SMIVI. In AUROC, the combined scores showed significantly better diagnostic performance compared to BI-RADS alone (p

Background: The purpose of this study was to determine the detailed characteristics of dizziness in patients with de novo Parkinson’s disease (PD) and the clinical implications of dizziness. Methods: Ninety-three people with de novo PD were enrolled between July 2017 and August 2022 for this retrospective study. Using each representative scale, various motor and non-motor symptoms were assessed. In addition, clinical manifestations of dizziness in those patients, including its presence, type, frequency, and duration of occurrence, were investigated. Results: Thirty-nine patients with de novo PD reported dizziness, with presyncope being the most common (38%). The most common frequency was several times a week (51%). The most common duration was a few seconds (67%). Multivariable logistic regression analysis showed that dizziness was more common in women than in men {odds ratio (OR): 3.3601, 95% confidence interval (CI): 1.0820–10.4351, p = 0.0361}. Dizziness was significantly related to non-motor symptoms of low global cognition (OR: 0.8372, 95% CI: 0.7285–0.9622, p = 0.0123) and severe autonomic dysfunction (OR: 1.1112, 95% CI: 1.0297–1.1991, p = 0.0067). A post-hoc analysis revealed that dizziness was only associated with cardiovascular dysautonomia (adjusted OR: 10.2377, 95% CI: 3.3053–31.7098, p < 0.0001) among several domains of dysautonomia. Conclusions: About 42% of patients with de novo PD complained of dizziness. The occurrence of dizziness in those people was highly associated with female gender women, cognitive impairment, and cardiovascular dysautonomia. These results suggest that clinicians should pay close attention when patients with PD complain of dizziness.

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 Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

Abstract The risk factors of mild cognitive impairment (MCI) in patients with de novo Parkinson’s disease (PD) remain unclear. Therefore, the objective of this study was to compare motor and non-motor symptoms between de novo patients with PD with and without MCI. Moreover, detailed relationships between each cognitive deficit and other clinical characteristics in de novo patients with PD were investigated. Consecutive patients with de novo PD were retrospectively enrolled in this study. Motor symptoms were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) part-III and the Hoehn and Yahr (HY) stage. Non-motor symptoms including depression, anxiety, fatigue, and autonomic dysfunction were measured using representative questionnaires. Motor symptoms, depression, and dysautonomia were associated with MCI in de novo patients with PD. Compared with the non-MCI group with PD, the MCI group with PD had higher scores of UPDRS-III, HY stage, depression, and dysautonomia, but not fatigue or anxiety. Both UPDRS-III and HY stage were significantly linked to all cognitive deficits except attention. Logistic regression analysis showed that depression was associated with memory, visuospatial, and executive impairment, and dysautonomia was related to visuospatial and executive impairment. The results of this study suggest that cognitive impairment in PD might have a different relationship pattern to the motor and some non-motor symptoms.

Abstract Although central retinal artery occlusion (CRAO) has its own defining pathomechanism and clinical characteristics, morphologic feature of the optic nerve head (ONH) during its later stage is not diagnostic, which makes it difficult to differentiate CRAO from other optic neuropathies. This cross-sectional study was performed to investigate the differences in the topographic morphology of the ONH in eyes with normal-tension glaucoma (NTG) and CRAO. Thirty-one eyes with NTG; 31 eyes with CRAO; and 31 healthy fellow eyes of the subjects with CRAO were included. ONH morphology was evaluated by measuring horizontal rim width (HRW), minimal rim width in the selected horizontal image (MRW), and lamina cribrosa curvature index (LCCI) in horizontal B-scan images obtained using enhanced depth-imaging optical coherence tomography. HRW was smaller and LCCI was larger in NTG eyes than in both CRAO and healthy fellow eyes (both P

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.

Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple‐negative breast cancers require distinct therapeutic approaches because of their different amounts of autophagy flux. We identified that autophagy flux was inhibited in triple‐negative breast cancer (TNBC) CSCs. Moreover, miRNA‐181a (miR‐181a) expression is upregulated in both TNBC CSCs and patient tissues. Autophagy‐related 5 (ATG5) and autophagy‐related 2B (ATG2B) participate in the early formation of autophagosomes and were revealed as targets of miR‐181a. Inhibition of miR‐181a expression led to attenuation of TNBC stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR‐181a‐regulated mechanism in TNBC. Promoting tumor‐suppressive autophagy using curcumin may be a potential method for the treatment of TNBC.

Abstract Background Neural stem cells (NSCs) have the ability to generate a variety of functional neural cell types and have a high potential for neuronal cell regeneration and recovery. Thus, they been recognized as the best source of cell therapy for neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to the possibility of paracrine effect-based therapeutic mechanisms and easier clinical accessibility, extracellular vesicles (EVs), which possess very similar bio-functional components from their cellular origin, have emerged as potential alternatives in regenerative medicine. Material and methods EVs were isolated from human fibroblast (HFF) and human NSC (F3 cells). The supernatant of the cells was concentrated by a tangential flow filtration (TFF) system. Then, the final EVs were isolated using a total EV isolation kit. Results In this study, we demonstrate the potential protective effect of human NSC-derived EVs, showing the prevention of PD pathologies in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo mouse models. Human NSC and F3 cell (F3)-derived EVs reduced the intracellular reactive oxygen species (ROS) and associated apoptotic pathways. In addition, F3-derived EVs induced downregulation of pro-inflammatory factors and significantly decreased 6-OHDA-induced dopaminergic neuronal loss in vivo. F3 specific microRNAs (miRNAs) such as hsa-mir-182-5p, hsa-mir-183-5p, hsa-mir-9, and hsa-let-7, which are involved in cell differentiation, neurotrophic function, and immune modulation, were found in F3-derived EVs. Conclusions We report that human NSC-derived EVs show an effective neuroprotective property in an in vitro transwell system and in a PD model. The EVs clearly decreased ROS and pro-inflammatory cytokines. Taken together, these results indicate that NSC-derived EVs could potentially help prevent the neuropathology and progression of PD. Graphical Abstract

Abstract We evaluated the physiological benefits of performing lung recruitment maneuver (LRM) in the semi-lateral position compared in the supine position. Seventy-nine patients undergoing laparoscopic prostatectomy were randomly assigned to either the supine or semi-lateral group according to body position during the LRM. At the end of surgery, LRM (35 cmH2O for 20 s) was performed twice in the assigned posture. The primary outcome was the maximal decrease in systolic arterial pressure during LRM. Secondary outcomes were changes in PaO2/FiO2 and the regional lung volume distribution after LRM. The decrease in systolic arterial pressure during the LRM was significantly higher in the supine group than in the semi-lateral group (mean ± standard deviation, [−] 27.6 ± 14.6% vs. [−] 18.6 ± 9.9%, P = 0.001). Improvement in PaO2/FiO2 ratio after the LRM was evident in both groups but was more prominent in the semi-lateral group than in the supine group (median [interquartile range], 39.3% [20.2, 63.6] vs. 18.2% [8.4, 29.2], P = 0.001). Among the horizontal lung divisions, regional lung volume in the most dependent portion (the dorsal division) was significantly increased after the LRM only in the semi-lateral group (P = 0.024). Performing lung recruitment in a semi-lateral position protected against hemodynamic deterioration during the LRM and increased regional lung ventilation in the dependent portion of the lung, leading to an improvement in arterial oxygenation after laparoscopic procedures. Trial registration Clinical Research Information Service ( https://cris.nih.go.kr/ ). Identifier: KCT0003756.

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.

Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary−PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary−PDX integrity.

Within the human body, the intricate network of blood vessels plays a pivotal role in transporting nutrients and oxygen and maintaining homeostasis. Bioprinting is an innovative technology with the potential to revolutionize this field by constructing complex multicellular structures. This technique offers the advantage of depositing individual cells, growth factors, and biochemical signals, thereby facilitating the growth of functional blood vessels. Despite the challenges in fabricating vascularized constructs, bioprinting has emerged as an advance in organ engineering. The continuous evolution of bioprinting technology and biomaterial knowledge provides an avenue to overcome the hurdles associated with vascularized tissue fabrication. This article provides an overview of the biofabrication process used to create vascular and vascularized constructs. It delves into the various techniques used in vascular engineering, including extrusion-, droplet-, and laser-based bioprinting methods. Integrating these techniques offers the prospect of crafting artificial blood vessels with remarkable precision and functionality. Therefore, the potential impact of bioprinting in vascular engineering is significant. With technological advances, it holds promise in revolutionizing organ transplantation, tissue engineering, and regenerative medicine. By mimicking the natural complexity of blood vessels, bioprinting brings us one step closer to engineering organs with functional vasculature, ushering in a new era of medical advancement.

Abstract Following the permanent shutdown of Kori Unit 1 in June 2017, the Republic of Korea has been preparing for full‐scale decommissioning work. In addition, the design life of 12 units will expire by 2030. If decommissioning begins without initially extending the lifespan of nuclear reactors, massive amounts of decommissioning wastes will be generated in a short period. The total amount of radioactive wastes generated during the dismantling of a pressurized water reactor is estimated as 6200 tons, and approximately 70% of the total radioactive wastes are classified as metal wastes. Self‐disposal through the decontamination of contaminated metals can contribute to the economic feasibility of decommissioning nuclear power plants because it can reduce the disposal cost of medium‐ and low‐level radioactive wastes. Therefore, this study evaluated the possibility of self‐disposal of steam generators that may occur during future decommissioning. The radioactivity analysis data on transferring the replaced steam generator of Hanul Unit 1 were used as the source term. The decontamination factor was calculated by applying 200 units from 1200 to 2000, and the radiation dose was evaluated using the RESRAD‐RECYCLE code. Consequently, the single‐nuclide concentration and sum of the allowable concentration fraction for mixed radionuclides at a decontamination factor of 1400 were below the regulatory requirements; however, the dose evaluation results exceeded the allowable dose in some scenarios. The decontamination factor was 2000, when the dose evaluation results for all scenarios met the regulatory requirements.

A case of a 30-year-old man who was admitted following a penetrating neck injury is presented. A clinical examination and operative findings identified semi-comatose mentality, neck muscle laceration, and transection of the left common carotid and vertebral arteries and the internal jugular vein. During the operation, the carotid arteries were repaired by interposition grafting, and the internal jugular vein was ligated. The vertebral artery was managed by interventional embolization. Although the patient had some neurological deficit, he was discharged on postoperative Day 52. This surgical case prompted a discussion regarding neurological outcomes, and surgical and endovascular treatment following vascular neck injury.

Electronic cigarette (e-cigarette) or vaping product use-associated lung injury (EVALI) has emerged as a social issue as e-cigarette use is rapidly increasing worldwide and is related to many deaths in the United States. To our knowledge, this is the first case report of EVALI in South Korea of a 24-year-old man with acute respiratory symptoms and a history of e-cigarette use. Chest CT revealed diffuse bilateral ground-glass opacities with subpleural sparing, airspace consolidation, and centrilobular micronodules as typical patterns of EVALI with organizing pneumonia and diffuse alveolar damage. Infection was excluded with meticulous laboratory examinations, and the patients’ illnesses were not attributed to other causes. EVALI was diagnosed by meeting the diagnostic criteria with consistent clinico-radiologic findings through a multidisciplinary approach. Radiologists should have good knowledge of EVALI radiologic findings and play a cardinal role in the proper diagnosis and management of EVALI.

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

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.

Endothelial progenitor cell (EPC)-based stem cell therapy is a promising therapeutic strategy for vascular diseases. However, continuous in vitro expansion for clinical studies induces the loss of EPC functionality due to aging. In this study, we investigated the effects of StemRegenin-1 (SR-1), an antagonist of aryl hydrocarbon receptor (AhR), on replicative senescence in EPCs. We found that SR-1 maintained the expression of EPC surface markers, including stem cell markers, such as CD34, c-Kit, and CXCR4. Moreover, SR-1 long-term-treated EPCs preserved their characteristics. Subsequently, we demonstrated that SR-1 showed that aging phenotypes were reduced through senescence-associated phenotypes, such as β-galactosidase activity, SMP30, p21, p53, and senescence-associated secretory phenotype (SASP). SR-1 treatment also increased the proliferation, migration, and tube-forming capacity of senescent EPCs. SR-1 inhibited the AhR-mediated cytochrome P450 (CYP)1A1 expression, reactive-oxygen species (ROS) production, and DNA damage under oxidative stress conditions in EPCs. Furthermore, as a result of CYP1A1-induced ROS inhibition, it was found that accumulated intracellular ROS were decreased in senescent EPCs. Finally, an in vivo Matrigel plug assay demonstrated drastically enhanced blood vessel formation via SR-1-treated EPCs. In summary, our results suggest that SR-1 contributes to the protection of EPCs against cellular senescence.

This study investigated the protective effect of glutathione (GSH), an antioxidant drug, against doxorubicin (DOX)-induced cardiotoxicity. Human cardiac progenitor cells (hCPCs) treated with DOX (250 to 500 nM) showed increased viability and reduced ROS generation and apoptosis with GSH treatment (0.1 to 1 mM) for 24 h. In contrast to the 500 nM DOX group, pERK levels were restored in the group co-treated with GSH and suppression of ERK signaling improved hCPCs’ survival. Similarly to the previous results, the reduced potency of hCPCs in the 100 nM DOX group, which did not affect cell viability, was ameliorated by co-treatment with GSH (0.1 to 1 mM). Furthermore, GSH was protected against DOX-induced cardiotoxicity in the in vivo model (DOX 20 mg/kg, GSH 100 mg/kg). These results suggest that GSH is a potential therapeutic strategy for DOX-induced cardiotoxicity, which performs its function via ROS reduction and pERK signal regulation.

Abstract Background Dynamically altered microglia play an important role in the progression of Alzheimer’s disease (AD). Here, we found a close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake on [18F]fluorodeoxyglucose (FDG) PET. Methods We used an AD animal model, 5xFAD, to analyze hippocampal glucose metabolism using both animal FDG PET and ex vivo FDG uptake test. Cells of the hippocampus were isolated to perform single-cell RNA-sequencing (scRNA-seq). The molecular features of cells associated with glucose metabolism were analyzed at a single-cell level. In order to apply our findings to human brain imaging study, brain FDG PET data obtained from the Alzheimer’s Disease Neuroimaging Initiative were analyzed. FDG uptake in the hippocampus was compared according to the diagnosis, AD, mild cognitive impairment, and controls. The correlation analysis between hippocampal FDG uptake and soluble TREM2 in cerebrospinal fluid was performed. Results In the animal study, 8- and 12-month-old 5xFAD mice showed higher FDG uptake in the hippocampus than wild-type mice. Cellular FDG uptake tests showed that FDG activity in hippocampal microglia was increased in the AD model, while FDG activity in non-microglial cells of the hippocampus was not different between the AD model and wild-type. scRNA-seq data showed that changes in glucose metabolism signatures including glucose transporters, glycolysis and oxidative phosphorylation, mainly occurred in microglia. A subset of microglia with higher glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. In the human imaging study, we found a positive association between soluble TREM2 and hippocampal FDG uptake. FDG uptake in the hippocampus at the baseline scan predicted mild cognitive impairment conversion to AD. Conclusions We identified the reconfiguration of microglial glucose metabolism in the hippocampus of AD, which could be evaluated by FDG PET as a feasible surrogate imaging biomarker for microglia-mediated inflammation.

Background: The purpose of this study was to investigate whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can be used as supplemental tools to differentiate between uterine myomas and sarcomas. Methods: From January 2000 to May 2020, patients diagnosed with uterine sarcoma or myoma after surgery at the Catholic University Hospital of Daegu were enrolled in the study. The age and preoperative hematologic findings including hemoglobin, white blood cell count, neutrophils, lymphocytes, platelet counts and lactate dehydrogenase were retrospectively investigated. Results: A total of 366 patients, including 40 uterine sarcoma patients and 326 uterine myoma patients, were included in the study. Among the hematologic findings, NLR and PLR showed statistically significant differences between uterine sarcoma and myoma. The probability of sarcoma was high when NLR was ≥2.6 and PLR was ≥150.0. When NLR was ≥2.6, the odds ratio of uterine sarcoma risk was 9.761 (95% confidence interval [CI]: 3.950–24.120, P < 0.001). When PLR was ≥150, the odds ratio of uterine sarcoma risk was 3.502 (95% CI: 1.528–8.027, P = 0.003). If NLR was above their cut-offs, the sensitivity of uterine sarcoma diagnosis was 60% and specificity was 83.4%. Identically, PLR was 60% and 73.3%, respectively. Conclusion: NLR and PLR are useful supplemental tools for the differential diagnosis of uterine myoma and sarcoma. Therefore, more expensive and accurate imaging studies, such as magnetic resonance imaging, can be more effectively recommended when these hematologic findings are used together with pelvic ultrasonography.

Purpose This study aimed to evaluate the reproducibility and diagnostic performance of a quantitative parameter of superb microvascular imaging (SMI) in real-time breast ultrasonography (US) for differentiating benign from malignant breast masses. Methods Eighty-seven breast masses in 75 patients who underwent both B-mode US and SMI before US-guided core needle biopsy were included in this study. Two radiologists performed B-mode US and measured the vascular index (VI) of SMI respectively for each lesion in real time. Intraobserver and interobserver agreements were analyzed for the VI of SMI. The diagnostic performance of B-mode US using the Breast Imaging Reporting and Database System lexicon and combined use with the VI of SMI was evaluated compared to pathology. Results The median VI of malignant masses (n=32) was significantly higher than that of benign masses (n=55) (7.6% and 2.6%, respectively; P

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.

Although somatic cell nuclear transfer (SCNT) is frequently employed to produce cloned animals in laboratories, this technique is expensive and inefficient. Therefore, the handmade cloning (HMC) technique has been suggested to simplify and advance the cloning process, however, HMC wastes many oocytes and leads to mitochondrial heteroplasmy. To solve these problems, we propose a modified handmade cloning (mHMC) technique that uses simple laboratory equipment, i.e., a Pasteur pipette and an alcohol lamp, applying it to porcine embryo cloning. To validate the application of mHMC to pig cloning, embryos produced through SCNT and mHMC are compared using multiple methods, such as enucleation efficiency, oxidative stress, embryo developmental competence, and gene expression. The results show no significant differences between techniques except in the enucleation efficiency. The 8-cell and 16-cell embryo developmental competence and Oct4 expression levels exhibit significant differences. However, the blastocyst rate is not significantly different between mHMC and SCNT. This study verifies that cloned embryos derived from the two techniques exhibit similar generation and developmental competence. Thus, we suggest that mHMC could replace SCNT for simpler and cheaper porcine cloning.